SCHOLAR Study Guide CfE Higher Human Biology Unit 4 ... · SCHOLAR Study Guide CfE Higher Human...

SCHOLAR Study Guide

CfE Higher Human BiologyUnit 4: Immunology and PublicHealth

Authored by:Eoin McIntyre (Previously Auchmuty High School)

Reviewed by:Sheena Haddow (Perth College)

Previously authored by:Mike Cheung

Eileen Humphrey

Eoin McIntyre

Jim McIntyre

Heriot-Watt University

Edinburgh EH14 4AS, United Kingdom.

First published 2014 by Heriot-Watt University.

This edition published in 2016 by Heriot-Watt University SCHOLAR.

Copyright © 2016 SCHOLAR Forum.

Members of the SCHOLAR Forum may reproduce this publication in whole or in part foreducational purposes within their establishment providing that no profit accrues at any stage,Any other use of the materials is governed by the general copyright statement that follows.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval systemor transmitted in any form or by any means, without written permission from the publisher.

Heriot-Watt University accepts no responsibility or liability whatsoever with regard to theinformation contained in this study guide.

Distributed by the SCHOLAR Forum.

SCHOLAR Study Guide Unit 4: CfE Higher Human Biology

1. CfE Higher Human Biology Course Code: C740 76

ISBN 978-1-909633-19-3

Print Production and Fulfilment in UK by Print Trail www.printtrail.com

AcknowledgementsThanks are due to the members of Heriot-Watt University’s SCHOLAR team who planned andcreated these materials, and to the many colleagues who reviewed the content.

We would like to acknowledge the assistance of the education authorities, colleges, teachersand students who contributed to the SCHOLAR programme and who evaluated these materials.

Grateful acknowledgement is made for permission to use the following material in theSCHOLAR programme:

The Scottish Qualifications Authority for permission to use Past Papers assessments.

The Scottish Government for financial support.

The content of this Study Guide is aligned to the Scottish Qualifications Authority (SQA)curriculum.

All brand names, product names, logos and related devices are used for identification purposesonly and are trademarks, registered trademarks or service marks of their respective holders.

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Contents

1 Non-specific defences 11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.2 The immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.3 Non-specific defences - physical and chemical . . . . . . . . . . . . . . 41.4 The inflammatory response . . . . . . . . . . . . . . . . . . . . . . . . 61.5 Non-specific cellular responses . . . . . . . . . . . . . . . . . . . . . . 101.6 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141.7 Extended response question . . . . . . . . . . . . . . . . . . . . . . . . 151.8 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2 Specific cellular defences 172.1 Immune surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182.2 Clonal selection theory . . . . . . . . . . . . . . . . . . . . . . . . . . . 202.3 T- and B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232.4 The action of T-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . 262.5 The action of B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . 272.6 Immunological memory . . . . . . . . . . . . . . . . . . . . . . . . . . . 302.7 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322.8 Extended response question . . . . . . . . . . . . . . . . . . . . . . . . 332.9 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

3 The transmission and control of infectious diseases 353.1 Infectious diseases caused by pathogens . . . . . . . . . . . . . . . . . 363.2 Methods of transmission of pathogens . . . . . . . . . . . . . . . . . . 423.3 Control of spread of pathogens . . . . . . . . . . . . . . . . . . . . . . 443.4 Epidemiological studies of infectious diseases . . . . . . . . . . . . . . 493.5 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533.6 Extended response question . . . . . . . . . . . . . . . . . . . . . . . . 533.7 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

4 Active immunisation 554.1 Active immunisation and vaccination . . . . . . . . . . . . . . . . . . . 564.2 Herd Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634.3 Immunisation programmes . . . . . . . . . . . . . . . . . . . . . . . . . 674.4 The evasion of specific immune responses by pathogens . . . . . . . . 704.5 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784.6 Extended response question . . . . . . . . . . . . . . . . . . . . . . . . 794.7 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

5 End of unit test 81

ii CONTENTS

Glossary 85

Answers to questions and activities 871 Non-specific defences . . . . . . . . . . . . . . . . . . . . . . . . . . . 872 Specific cellular defences . . . . . . . . . . . . . . . . . . . . . . . . . 913 The transmission and control of infectious diseases . . . . . . . . . . . 954 Active immunisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 985 End of unit test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

© HERIOT-WATT UNIVERSITY

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Topic 1

Non-specific defences

Contents

1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.2 The immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

1.3 Non-specific defences - physical and chemical . . . . . . . . . . . . . . . . . . 4

1.4 The inflammatory response . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1.4.1 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1.4.2 The cellular basis of inflammation . . . . . . . . . . . . . . . . . . . . . 7

1.5 Non-specific cellular responses . . . . . . . . . . . . . . . . . . . . . . . . . . 10

1.5.1 Phagocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

1.5.2 Natural killer (NK) cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

1.6 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

1.7 Extended response question . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1.8 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Prerequisite knowledge

You should already know about:

• defences against disease (phagocytosis, antibodies, vaccination);

• diseases (viruses, bacteria, fungi, parasites);

• hygiene (personal, sexual, food, water).

Learning objectives

By the end of this topic, you should be able to:

• state that the body’s capacity to protect itself against pathogens, some toxins andcancer cells is achieved by means of the immune system;

• describe the nature of the body’s chemical and physical defences againstpathogens;

• describe the inflammatory response;

• describe the non-specific cellular responses.

2 TOPIC 1. NON-SPECIFIC DEFENCES

1.1 Introduction

If it were possible that an intelligent life-form from another planet in our galaxy couldvisit Earth, and that we could communicate with it, we might ask what it thought ofthe place. If we enquired about what it considered to be the dominant life-form, wemight be surprised at the answer because it has been estimated that 90% of the energyprocessed by organisms on the planet is done so by bacteria. Likewise, the totalbiomass of bacteria on the planet is thought to exceed that of all other living thingsput together. With an average size of 1µm, they have found niches virtually everywhere,from the bedrock, to the clouds, the deep sea floor, and hot springs. And, of course,nine tenths of the cells within our bodies are bacteria.

It may be a bit disconcerting to conceive of ourselves as habitats, but we are just that(and a very attractive one!) to bacteria and other microbes. Our tissues are warmand constantly bathed in nutrient- and oxygen-rich fluid, conditions which are perfect formicrobes to thrive in. Much of this is true of all multicellular organisms, and so, to existat all, they have had to evolve methods of countering colonisation by microbes.

A common misconception is that all microbes are potential pathogens, but that is farfrom true. We could not live a healthy life without our varied and complex gut flora ofbacteria, and trees could not absorb nutrients from the soil without the aid of the fungalthreads attached to their roots.

It should also be remembered that although we tend to think of bacteria in relation toinfection, the heterotrophic organisms that test our defences come from all categories,so we have to be able to defend ourselves against viruses (e.g. flu), bacteria (e.g.pneumonia), fungi (e.g. athlete’s foot), protozoans (e.g. malaria), and even quite largeanimals (e.g. tapeworms). We will leave the discussion about whether viruses are aliveto another time.

This unit addresses the natural defences that our bodies have against microbial attackin the form of our immune system, and the precautions that human societies put in placeto counter the spread of disease in the shape of public health measures.

1.2 The immune system�

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Learning objective

By the end of this section, you should be able to:

• state that the function of the immune system is to protect the body againstpathogens, some toxins and cancer cells.

The body’s capacity to protect itself against pathogens, some toxins and cancer cellsis achieved by means of the immune system. We have three lines of defence againstattack by pathogens.

1. The first line of defence is non-specific - an external barrier of skin and mucousmembranes and the secretions that they produce. The skin provides a physicalbarrier of dry, dead cells and mildly acidic conditions. Areas of the body which


TOPIC 1. NON-SPECIFIC DEFENCES 3

are not protected by this barrier, such as the eyes and mouth, have secretions inthe form of tears and saliva, which contain a variety of antimicrobial enzymes, e.g.lysozyme which degrades bacterial cell walls.

2. The second line of defence is also non-specific, and comes into play when thefirst line of defence is breached and an intruder, such as a bacterium, gets intothe body tissues. The intruder produces chemical signals that are detected by avariety of white blood cells which will attack it in a number of ways, e.g. neutrophilsand macrophages which engulf the invading cells, and natural killer cells (NK cells)which release chemicals that cause their death. An area of inflammation indicatesthat the second line of defence has been deployed.

3. The third line of defence, the specific immune response (to be covered in Topic 2)comes into play at the same time as the second line of defence. Here, the immunesystem directly targets the invader, which can be any organism or substance thatcarries foreign molecules.

Immunity is the ability of the body to resist or overcome an infection by a pathogen andcan be either innate or acquired. Innate immunity is inborn, non-specific, and does notchange over time. Examples include:

• phagocytosis by phagocytes;

• skin epithelial cells;

• mucus membranes of the lungs and gut;

• ciliated cells of the respiratory tract;

• lysozyme in tears.

Acquired immunity develops throughout a person’s life time and can be induced eithernaturally or artificially. It involves another group of white blood cells, lymphocytes,which respond to marker chemicals on the surface of the foreign cells called antigens,producing antibodies against them. A second response is the production of memorycells, which enable the immune system to react more quickly and vigorously to re-infection by pathogens.

The immune system: Questions

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Q1: What is the function of the immune system?

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Q2: List two examples of non-specific first line of defence against diseases.

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Q3: What is the function of the lysozyme in tears?

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Q4: Explain the term ’innate immunity’ and list two examples.

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Q5: What is a phagocyte?

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1.3 Non-specific defences - physical and chemical�

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Learning objective


• give examples of the body’s chemical and physical defences against pathogens;

• explain that epithelial cells form a physical barrier and produce secretionsagainst infection.

You should remember from Unit 1 that epithelial cells provide the inner and outer liningsof body cavities, for example the stomach and the urinary tract. They act as the barrierbetween the external environment and the body tissues.

The skin is considered to be the first line of defence for the human body. Its structureensures that very few microorganisms can penetrate unless it is damaged. In addition,the secretion of antimicrobial chemicals by the skin and tear glands offers additionalprotection.

The outermost part of the skin, or epidermis, is a multilayered tissue. At its base arestem cells which divide to continually replace the layers above it. As they move from thebase towards the surface, the cells gradually change their structure to give the epidermisits tough elastic properties. The outer layer consists of dead cells, which are regularlysloughed off as a result of friction with the environment. These are dry and provide anenvironment which is inhospitable to microbes.

Associated with the hair follicles on the skin are the sebaceous glands, which secrete thewaxy sebum that keeps the skin supple and contains fatty acids which have antimicrobialproperties. Similarly, earwax contains chemicals which inhibit the growth of pathogenicbacteria and fungi.

Certain types of epithelial cells secrete fluids that are necessary for processes such asdigestion, protection, excretion of waste products and the regulation of the metabolicprocesses of the body, e.g. the goblet cells which secrete mucus.

Epithelial tissues containing goblet cells



Some epithelial tissues are specialised to secrete specific substances, such asenzymes, hormones and lubricating fluids, to defend against infections. The gobletcells in the trachea secrete mucus which, being a sticky substance, is able to adhere toforeign particles, thus holding them on the surface. This adhesion allows the cilia whichline the bronchi to sweep the mucus, with its entrapped particles, up into the pharynxwhere it is swallowed. Antimicrobial chemicals are also found in the mucus, secreted bythe epithelial linings of the respiratory and upper gastrointestinal tracts.

The body can also provide other physical and chemical defences:

• tiny hairs at the entrance to the nose;

• cough and sneeze reflexes;

• acid secretions which kill microbes, e.g. stomach;

• the so-called ’friendly’ bacteria which are the many harmless microbes normallyfound on the skin and epithelial linings that are exposed to the externalenvironment - by means of a variety of mechanisms, these microbes can suppressthe growth of other potentially more dangerous and harmful ones.

Non-specific defences - physical and chemical: Questions

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Q6: State two ways in which the skin is a physical barrier to microbes.

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Q7: State two ways in which the epithelium presents a chemical barrier to microbes.

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1.4 The inflammatory response�

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Learning objective


• state that mast cells release histamine;

• explain that histamine causes vasodilation and increases capillary permeability;

• state that mast cells also secrete cytokines which act as signalling molecules;

• explain that the increased blood flow and the secretion of cytokines lead to:

◦ accumulation of phagocytes such as macrophages and neutrophils;

◦ delivery of antimicrobial proteins and clotting elements to the site ofinfection/damage.

1.4.1 Inflammation

We are all familiar with the reddening which follows the infection of a scratch, bite orsting. However, in medical terms, inflammation is a more complex issue. It is a responseof the immune system to an infection or irritation. Some 2000 years ago, inflammationwas characterised into:

• rubor - redness;

• calor - heat;

• tumour - swelling;

• dolo - pain;

• functio laesa, the fifth sign of inflammation, which results in the dysfunction of theorgans involved.



Main events in the inflammatory response

Go online10 min

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1.4.2 The cellular basis of inflammation

The main purpose of the complex inflammatory process is to bring fluids, proteins andcells from the blood to the damaged tissues. It should be remembered that the fluid thatbathes the cells of the body’s tissues and organs lacks most of the proteins and cellsthat are found in the blood because they are not able to pass through the capillary walls.Thus, to combat damage and infections, there must be mechanisms which allow theseproteins and cells to move out of the blood circulation and into the surrounding tissuefluid. This process can be broken down into six stages.

Stage 1: The action of mast cells

Mast cells are found in connective tissue, where they cluster around blood vessels andnerves. They are most common where our tissues meet the outside world, e.g. skin, gut,mouth, eyes and nose. Although they resemble certain white blood cells and, like them,are produced by stem cells in the bone marrow, they are derived from a different cellline. Perhaps best known for mediating allergies, they also play a key role in protectionagainst infection. They are activated by chemicals that are released during an infectionor from damaged cells, as a result of which they release histamine in large quantities.



A mast cell

Stage 2: Vasodilation and increased capillary permeability

Histamine is a small, organic, nitrogenous molecule which has many roles in the body.In the inflammatory response, it stimulates the arterioles of the affected area to dilate,increasing blood flow into the capillary beds, and the walls of the capillaries to becomemore permeable, allowing plasma, proteins and white blood cells (neutrophils) to passthrough. Within minutes of an injury, this is noticeable as a swelling and reddening ofthe area, and a feeling of heat.

Stage 3: Secretion of cytokines

The mast cells and the neutrophils also release a type of signalling compound calledcytokines. Like histamine, these have a wide range of roles in the body, but in this casethey act to attract another type of white blood cell, monocytes, to the area.

Stage 4: Phagocytosis

Once in the tissue, the neutrophils begin the removal of invading bacteria byphagocytosis. They are soon joined by the monocytes, which mature intomacrophages and then clean up the damaged area by engulfing cell debris andbacteria by phagocytosis. After digestion is complete, the identifying surface molecules(antigens) of invading cells are transported to the surface of the macrophages wherethey assist the other cells of the immune system to develop protection against theinvader.

The term ’phagocyte’ is used to refer to a general grouping which includes macrophages,neutrophils and mast cells, all of which are capable of phagocytosis, but which differ inother respects.

Stage 5: The complement system

The complement system is so-called because it helps, and indeed amplifies, the actionof the phagocytes in combating infection. It comprises over 25 small proteins found inthe blood, which are synthesised by the liver. These remain in an inactive form untilstimulated by one of several triggers; in particular the cascade is triggered if cells whichlack the surface proteins typical of the body are encountered.



Activation of the first complement protein leads to activation of the second, whichactivates the third, and so on, resulting in a cascade effect. These substances haveseveral basic functions, including enhancing phagocytosis, attracting macrophages andneutrophils, and rupturing the membranes of microbes.

Stage 6: Clotting elements and the coagulation system

The increased permeability of the capillary walls leads to an increased flow of proteins(’clotting elements’) as well as white blood cells into the tissues, and a second cascadesystem (the ’coagulation system’) becomes active. In the infected tissue, a chemical’tissue factor’ is released that initiates the cascade which results in the conversion of thesoluble protein fibrinogen to insoluble fibrin. The fibrin strands form a web which helpsto contain the infection and inflammation.

The cellular basis of inflammation: Questions

Go onlineQ8: Where are mast cells found?

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Q9: State two effects of the histamine released by mast cells.

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Q10: Name the chemical signalling molecule which is released by mast cells andneutrophils.

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Q11: Which type of white blood cells are attracted by this chemical?

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Q12: By what process do these cells remove bacteria from the site of infection?

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Q13: Name the cascade system which delivers antimicrobial proteins to the infectedsite.

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Q14: Name the soluble and insoluble proteins at the end of the coagulation system.

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1.5 Non-specific cellular responses�

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Learning objective


• state that the white blood cells involved in the non-specific response arephagocytes and natural killer (NK) cells;

• state that phagocytes and NK cells release cytokines;

• explain that cytokines stimulate the specific immune response;

• state that phagocytes recognise surface antigen molecules on pathogens;

• state that phagocytes destroy pathogens by phagocytosis;

• explain that phagocytosis is engulfing and digesting solid particles;

• state that NK cells induce pathogens to produce self-destructive enzymes;

• state that this process of induced self-destruction by enzymes is calledapoptosis.

The business of defending the body against foreign cells and molecules which havepenetrated the first line of defence falls to certain types of white blood cell. In thissection, we will consider the non-specific role of two groups: the phagocytes (monocytesand neutrophils) and natural killer (NK) cells.

1.5.1 Phagocytes

The name ’phagocyte’ is an umbrella term encompassing several types of white bloodcell and mast cells; their common features include their origin in the bone marrow, theirability to move about (motility) and their ability to carry out phagocytosis.



Phagocytosis: Steps

Go online10 min

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The two most important phagocytes are the white blood cells: neutrophils andmonocytes. A question to be asked is how do the phagocytes (and the complementsystem mentioned earlier) identify bacteria; what makes them stand out from the cells ofthe body itself? The answer lies in proteins located on the surface of the cell membrane.If a phagocyte encounters a cell which is lacking the protein markers typical of cellsbelonging to the body, then a response is triggered.

Neutrophils

Neutrophils make up two thirds of the white blood cells in the blood and are the maincells found in pus. They are attracted to the site of infection by the cytokines releasedby the damaged cells, arriving in large numbers within minutes. The neutrophils alsorelease cytokines themselves, but their immediate effect is the engulfing of bacteria.Their lifespan is short, being only 5-7 days in the circulation, and 1-2 days at an infectionsite. This reflects the fact that they cannot replenish the digestive enzymes with whichthey break down ingested bacteria.



Once they have engulfed bacteria, the neutrophils express signal molecules on their cellmembranes which identify them to the larger macrophages, which then consume themin turn. In addition, they secrete antimicrobial chemicals which kill bacteria by disruptingtheir cell walls.

Monocytes

Monocytes are the largest of the white blood cells; at up to 20µm they are nearlytwice the size of neutrophils. They are much less common than neutrophils, makingup only some 5% of the total white blood count. About half of the body’s complementof monocytes is held in reserve in the spleen, the other half circulating in the blood andmigrating into the tissues where they mature into macrophages capable of phagocytosis.

Attracted by cytokines that are released by neutrophils and damaged cells, additionalmonocytes migrate from the blood to an infection site and turn into macrophages. Theythen begin to engulf damaged cells, bacteria and ’old’ neutrophils. Unlike neutrophils,macrophages can live for several months. Also, they express the antigens of ingestedbacteria on their outer membranes to help the other white blood cells of the immunesystem (lymphocytes) identify the invaders and produce specific antibodies to combatthem.

Phagocytes: Questions

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Q15: Name the chemical produced by phagocytes and NK cells.

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Q16: What is the function of this chemical?

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Q17: By what do phagocytes recognise pathogens?

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Q18: What is phagocytosis?

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1.5.2 Natural killer (NK) cells

NK cells are attracted to the site of an infection (or a tumour) after about three days bythe cytokines released by the damaged cells. They identify infected cells and tumourcells by the presence of certain key surface chemicals and then release two types ofenzymes: perforin and a type of protease known as granzyme.

The perforin causes pores to develop in the cell membrane of the target cell so that thegranzyme can enter the cell and induce programmed cell death (apoptosis). The cellcontains apoptosis pathways which allow it to self-destruct by enzyme action and thusbe recycled in a controlled way; these pathways are activated by the granzymes and,critically, they also cause the destruction of the viruses in the cell. Like neutrophils, NKcells also secrete antimicrobial chemicals.



Action of a natural killer cell

Apoptosis: Steps

Go online5 min

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Apart from their role in non-specific response, phagocytes and NK cells are also involvedin the specific immune response (described later). After their action against invadingpathogens, they then secrete interleukin, a cytokine that stimulates the specific immuneresponse by activating T lymphocytes.



Natural killer (NK) cells: Questions

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Q19: What do the NK cells induce target cells to produce?

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Q20: What is the process of programmed self-destruction in cells called?

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1.6 Learning points

Summary

Physical and chemical defences

• The function of the immune system is to protect the body against pathogens,some toxins and cancer cells.

• Give examples of the body’s chemical and physical defences againstpathogens, e.g. sebum secreted onto the skin contains fatty acids withantimicrobial properties; the dry outer layers of the epidermis create anenvironment hostile to pathogens.

The inflammatory response

• Mast cells release histamine.

• Histamine causes vasodilation and increases capillary permeability.

• Mast cells also secrete cytokines which act as signalling molecules.

• The increased blood flow and the secretion of cytokines lead to:

◦ accumulation of phagocytes such as macrophages and neutrophils;◦ delivery of antimicrobial proteins and clotting elements to the site of

infection/damage.

Non-specific cellular responses

• The white blood cells involved in the non-specific response are phagocytesand natural killer (NK) cells.

• Phagocytes and NK cells release cytokines.

• Cytokines stimulate the specific immune response.

• Phagocytes recognise surface antigen molecules on pathogens.

• Phagocytes destroy pathogens by phagocytosis.

• Phagocytosis is engulfing and digesting solid particles.

• NK cells induce pathogens to produce self-destructive enzymes.

• The process of induced self-destruction by enzymes is called apoptosis.



1.7 Extended response question

The activity which follows presents an extended response question similar to the stylethat you will encounter in the examination.

You should have a good understanding of the inflammatory response before attemptingthe question.

You should give your completed answer to your teacher or tutor for marking, or try tomark it yourself using the suggested marking scheme.

Extended response question: The inflammatory response

Give an account of the inflammatory response. (8 marks)

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1.8 End of topic test

End of Topic 1 test

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Q21: Complete the sentences by matching the parts on the left and the right. (8 marks)

The immune system protects the body against cytokines.

Sebum on the skin contains fatty acids with a hostile environment.

Pathogens find the dry outer layers of the skin to be histamine.

Mast cells release clotting elements.

Histamine causes antimicrobial properties.

Cytokines act as pathogens.

Increased blood flow leads to delivery of signalling molecules.

Phagocytes are attracted by vasodilation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Q22: Complete the paragraphs by selecting words from the list. (10 marks)

The white blood cells involved in the �� response are �� and naturalkiller (��) cells. Both phagocytes and NK cells release �� whichstimulate the specific immune response.

Phagocytes target pathogens which they recognise by the �� molecules on theircell surface. They then destroy them by �� and digesting them in a processcalled ��.

The NK cells release �� which induce infected cells and pathogens to producethe �� enzymes of �� pathways.

Word list : antigen, apoptosis, cytokines, engulfing, enzymes, NK, non-specific,phagocytes, phagocytosis, self-destructive.



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Q23: What is the function of the immune system? (1 mark)

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Q24: State two ways in which the skin prevents infection. (2 marks)

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Q25: Name the cells which release histamine. (1 mark)

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Q26: State the functions of histamine. (2 marks)

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Q27: Name the signalling molecules released by these cells. (1 mark)

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Q28: State the function of the signalling molecules. (1 mark)

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Q29: What is delivered by the increased blood flow to the site of infection? (2 marks)

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Q30: Name the two types of white blood cells involved in the non-specific response. (1mark)

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Q31: How do phagocytes recognise pathogens? (1 mark)

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Q32: Describe the process of phagocytosis. (1 mark)

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Q33: What do NK cells induce infected cells and pathogens to produce? (1 mark)

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Q34: Name the process of programmed cell death. (1 mark)

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17

Topic 2

Specific cellular defences

Contents

2.1 Immune surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

2.2 Clonal selection theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

2.3 T- and B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

2.4 The action of T-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

2.5 The action of B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

2.6 Immunological memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

2.7 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32


2.9 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Learning objectives


• describe the immune surveillance system in terms of the cells involved and theirfunctions;

• explain clonal selection theory and its role in the specific immune response;

• describe the functions of T- and B-lymphocytes;

• explain the role of immunological memory in the development of immunity.

18 TOPIC 2. SPECIFIC CELLULAR DEFENCES

In the previous topic, the body’s general response to invasion by pathogens or otherdamage was described. This topic deals with the very sophisticated system which allowsthe body, once it has met a particular pathogen, to respond very promptly and efficientlyto a second (or later) invasion by that organism.

2.1 Immune surveillance�

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Learning objective


• describe the role of white blood cells as constantly monitoring the tissues;

• explain that pathogens, and other foreign cells or materials, are recognised bytheir antigens, which are molecules on their surfaces that activate the immunesystem;

• state that cytokines are released when tissues are damaged or invaded;

• explain that cytokines attract specific white blood cells (monocytes) to theinfected/damaged tissue;

• explain that some of these cells absorb pathogens and display fragments of theircell membranes on their surface.

The immune system operates by means of the activities of several different types of cell.It responds to the presence of pathogens, and other foreign cells or materials whichare recognised by their antigens; that is molecules on their surfaces which activate theimmune system.

The cells of the non-specific immune response are the mast cells, phagocytes andnatural killer (NK) cells, whereas the specific immune response operates by means ofthe B- and T-lymphocytes. These cells, along with red blood cells (erythrocytes) andplatelets (thrombocytes), are all produced by division of the multipotent stem cells in thered bone marrow (the haematopoietic stem cells). A simplified diagram of this familytree is shown below.


TOPIC 2. SPECIFIC CELLULAR DEFENCES 19

Haematopoiesis

The haematopoietic stem cells give rise to two families of cells, namely those formedfrom the common myeloid progenitor, and those from the common lymphoid progenitor.The myeloid group includes red blood cells (erythrocytes), thrombocytes (platelets),mast cells and the various white blood cells involved in the non-specific response.

Cells of the surveillance system

The cells involved in the specific immune response, namely the T- and B-lymphocytes,belong to the lymphoid family. An exception is the natural killer (NK) cell which, thoughbelonging to the lymphoid group, acts as part of the non-specific response.

The cells associated with the non-specific response provide a surveillance system in thefollowing ways:

1. mast cells are found within the tissues and respond within seconds to damage orinfection by releasing histamine;

2. neutrophils, which circulate in the blood, enter the tissues when the histaminereleased by the mast cells causes increased blood flow to the affected tissue,increasing permeability of the capillary walls - they are attracted to the damagedarea by chemical signals released by damaged cells;

3. the mast cells and neutrophils, as well as mopping up damaged cells and invadingpathogens by phagocytosis, also release cytokines which attract monocytes to thetissue - these mature into macrophages which engulf damaged cells, pathogens,and any neutrophils which are signalling that they have themselves engulfedpathogens;



4. some of the macrophages present fragments of the cell membrane of engulfedpathogens on their own cell surface - these cells migrate to the lymph nodes wherethe pathogen fragments, carrying their unique antigens, activate the B- and T-lymphocytes which are stored there.

Immune surveillance: Questions

Go onlineQ1: Name the cells of the nonspecific immune system which first respond to infectionand are located within the tissues.

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Q2: Name the cells of the nonspecific immune system which first respond to infectionand are located in the blood.

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Q3: Name the chemicals which attract monocytes to the damaged tissue.

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Q4: Where are the B- and T-lymphocytes stored?

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Q5: How do some of the cells that monocytes develop into identify pathogens to thespecific immune system?

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2.2 Clonal selection theory�

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Learning objective


• state that clonal selection theory explains the way in which lymphocytes aredeveloped to respond to specific antigens which invade the body;

• state that lymphocytes have a single type of receptor on the cell membranewhich is specific to one antigen;

• explain how antigen binding leads to repeated lymphocyte division, whichresults in a clonal population of lymphocytes.

The Theory

Clonal Selection Theory was proposed in 1957 by an Australian medical researcher,Frank Macfarlane Burnet, as an answer to the question: how do we account for theimmune system’s ability to produce antibodies in response to new antigens?

A radical feature of the theory was that the body actually has lymphocytes carryingantibodies for antigens which it has never encountered. Given the vast range of potential



antigens that exists, this seems highly improbable. However, subsequent research,most recently into the genes controlling the production of antibodies, has confirmedthe validity of Burnet’s concept and, indeed, it underpins our whole understanding of theoperation of the adaptive immune system. Several Nobel Prizes have been awarded forresearch in this field.

The steps in the development of lymphocytes which carry receptors specific to oneantigen is summarised below. As the process is similar in the B- and T-lymphocytes(covered in the next section), they have not been dealt with separately here.

Clonal selection theory: Steps

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1. In the red bone marrow, haematopoietic stem cells divide to produce daughtercells.

2. As a result of genetic rearrangement, during differentiation these immaturelymphocytes each develop a different antigen receptor on their cell membranes.

3. Those immature lymphocytes which carry a receptor that will bind with an antigenfrom the body’s own tissues are destroyed in the bone marrow.

4. The lymphocytes carrying other antigen receptors are released from the bonemarrow and move through the circulatory system to the lymph glands or thymusgland where they mature into inactive lymphocytes.

5. Most of these inactive lymphocytes will never encounter an antigen to match theirreceptor.

6. Inactive lymphocytes which do meet an antigen matching their receptor becomeactivated and divide to produce many clones of themselves.

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Genetic background to antibody variability

To understand better how the variability of the receptors (and the antibodies to whichthey are related) arises, it is necessary to delve a little into the genetic control of antibodyproduction. Antibodies (also known as immunoglobulins) exist in two forms, one whichis bound to the outer surface of the cell membrane of lymphocytes, and another whichis secreted by these cells and exists as soluble protein in the blood plasma, tissue fluidand lymph.

These antibody molecules are made up of four basic polypeptide chains that are codedfor by three genes which are located on three different chromosomes. Each of thesegenes is composed of many segments. In the course of differentiation, these segmentsare subject to such a degree of alternative splicing during DNA transcription that thereare approximately 3 × 1011 unique potential antibody molecules that could be expressedon the cell membrane. Only one of these would be found on any particular lymphocyte.

The development of immunity

The receptors on the inactive lymphocytes act like antibodies in that they specificallybind to a single antigen molecule. If this happens, then a series of changes are triggeredin the lymphocyte. The combination of gene segments becomes fixed, and only thatcombination will be used to produce antibodies by that cell and its clones.

The activated lymphocyte begins to divide to produce two types of cloned daughter cell:

1. plasma cells, which have extensive folded membrane layers in the cytoplasm thatare covered with ribosomes to produce large quantities of the polypeptides whichwill be formed into antibodies in the Golgi apparatus;

2. memory cells, which remain in the lymph glands ready to be activated bysubsequent encounters with the same antigen - during the first exposure to theantigen, e.g. during an infection, these cells undergo a considerable degree ofminor mutations and the mutants with the best match of receptor to antigen aremaintained, the being remainder destroyed - during a second infection, these cellsproduce a much more rapid and effective response.

Clonal selection theory: Questions

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Q6: Put the steps from clonal selection theory into the correct order.

• Those immature lymphocytes, which carry a receptor that will bind with an antigenfrom the body’s own tissues, are destroyed in the bone marrow.

• As a result of genetic rearrangement, during differentiation these immaturelymphocytes each develop a different antigen receptor on their cell membranes.

• Inactive lymphocytes, which do meet an antigen matching their receptor, becomeactivated and divide to produce many clones of themselves.

• Most of these inactive lymphocytes will never encounter an antigen to match theirreceptor.

• In the red bone marrow, haematopoietic stem cells divide to produce daughter cells.• The lymphocytes that carry other antigen receptors are released from the bone

marrow and move through the circulatory system to the lymph glands or thymusgland where they mature into inactive lymphocytes.



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Q7: What does clonal selection theory explain?

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Q8: To how many different types of antigen do the receptors on each lymphocyterespond?

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2.3 T- and B-lymphocytes�

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Learning objective


• state that lymphocytes respond specifically to antigens on foreign cells, cellsinfected by pathogens and toxins released by pathogens;

• state that T-lymphocytes have specific surface proteins that allow them todistinguish between the surface molecules of the body’s own cells and cellswith foreign molecules on their surface;

• explain that autoimmune diseases arise as a result of a failure of immune systemregulation, leading to a response by T-lymphocytes to self antigens;

• state that activated B-lymphocytes secrete antibodies into the blood and lymph;

• explain that allergies are a hypersensitive B-lymphocyte response to an antigenthat is normally harmless.

Distinguishing ’self-’ from ’non-self’ antigens

As was described in Section 2.1, T- and B-lymphocytes are produced by thehaematopoietic stem cells in the red bone marrow and they belong to the lymphoidgroup of cells. Both have the ability to respond to specific antigens, which may be: partof foreign cells; attached to the surface of cells which are infected by pathogens; ortoxins (biologically produced poisons). This response to specific antigens is achievedby the cells having receptor proteins on their cell membranes which are only capableof binding with that antigen. Given that lymphocytes which carry receptors for thebody’s own (’self’) antigens are eliminated before they can leave the bone marrow,this enables the lymphocytes collectively to distinguish between the foreign (’non-self’)antigens and those of the body’s own cells. The mechanism of antigen binding and thesubsequent response of the cell are the main differences between actions of the T- andB-lymphocytes.

Once released from the bone marrow, T- and B-lymphocytes differ in the locations wherethey mature. For T-lymphocytes it is the thymus gland which is found in front of the heartunderneath the sternum (breast bone); for B-lymphocytes it is small patches of cells in



the extensive network of lymph glands associated with the intestine. Once mature, thelymphocytes may be found throughout the body, but in particular they locate in the lymphglands and the spleen, where they can readily detect foreign antigens in the lymph andblood which are filtered through these organs.

Autoimmune disease

An autoimmune disease is a disorder in which the immune system is triggered by one ormore of the body’s own self antigens. What causes the immune system to no longerdistinguish between self and non-self antigens is unknown. One suggestion is thatsome microorganisms (such as bacteria or viruses) or drugs may induce some of thesechanges, especially in people who are genetically predisposed to develop autoimmunedisorders.

More than eighty such diseases have been identified and T-lymphocytes are principallyinvolved, although some disorders are caused by B-lymphocytes. Examples includeCeliac disease, Multiple sclerosis, Rheumatoid arthritis, and Type-1 diabetes.

Treatment is dependent on the nature of the disease: Type-1 diabetes is addressed bythe injection of the missing hormone (insulin); others may be controlled by reducing theimmune system’s response with immunosuppressive drugs.

Allergy

Allergies are very common. According to Allergy UK, one in four people in the UKsuffers from an allergy at some point in their lives. The numbers are increasing everyyear and up to half of those affected are children. Common allergies include hay feverand eczema although, strictly, these are symptoms of an allergy to grass pollen and asubstance such as latex. The most severe allergies cause anaphylactic shock, whichcan be rapidly fatal; although most often associated with foods, such as peanuts, orinsect stings, anaphylaxis can be caused in those who are susceptible by almost anyforeign substance.

An allergy is an immune response to substances in the environment that are usuallynot harmful. The causes of allergies are both genetic and environmental. Not onlyhas the immune system to separate self from non-self antigens, but it must not initiatea response to antigens from harmless sources such as food or pollen. For mostsubstances this works perfectly, but, occasionally, instead of ignoring a harmlessantigen, the B-lymphocytes respond to an otherwise harmless antigen and set theimmune response in motion.

When a person first encounters an antigen to which they are genetically susceptible,the cells that react in this sensitising exposure are B-lymphocytes. These secrete theantibody IgE (immunoglobulin E) which attaches to mast cells and activates them.

A second exposure to this antigen causes the mast cells to release large quantities ofhistamine and cytokines which, in turn, cause symptoms such the swelling of the tissues,irritation of the eyes and nose, and, in the most severe cases, the loss of blood pressurewhich is known as shock.



Mast cells: Steps

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1. The first time an allergy-prone person encounters an allergen such as ragweed. . .

2. . . .he or she makes large amounts of ragweed IgE antibody.

3. These IgE molecules attach themselves to mast cells.

4. The second time that person has a brush with ragweed the IgE-primed mastcells release granules and powerful chemical mediators, such as histamine andcytokines.

5. These chemical mediators cause the characteristic symptoms of allergy.

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T- and B-lymphocytes: Questions

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Q9: What substances trigger the immune response?

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Q10: How do T-lymphocytes distinguish between self and non-self antigens?

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Q11: What causes an autoimmune disease?

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Q12: State the reaction of B-lymphocytes to being activated.

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Q13: What causes an allergy?

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2.4 The action of T-lymphocytes�

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Learning objective


• state that one group of T-lymphocytes destroys infected cells by inducingapoptosis;

• state that another group of T-lymphocytes secrete cytokines that activate B-lymphocytes and phagocytes;

• explain that, when pathogens infect tissue, some phagocytes capture thepathogen and display fragments of its antigens on their surface;

• explain that these antigen-presenting cells activate the production of a clone ofT-lymphocytes that move to the site of infection under the direction of cytokines.

T-lymphocytes, of which there are several types, are so-called because they maturein the thymus gland (and the tonsils). T-lymphocytes (along with phagocytes) areresponsible for the cell-mediated response of the adaptive immune system. Two ofthese types are described here.

Cytotoxic T cells

Also known as Killer T cells, Cytotoxic T cells carry protein receptors on their cellmembrane like all T cells. This allows them to recognise specific antigens when theycome into contact with them on the surface of pathogens or cancer cells. Once attachedto the target cell, they use an enzyme to perforate the wall of the cell and then injectother enzymes which induce the cell to undergo apoptosis (programmed cell death).

Helper T cells

As their name implies, these cells assist other white blood cells, e.g. by inducing thematuration of B-lymphocytes into plasma cells and memory B cells, and the activationof cytotoxic T cells and macrophages. Their receptors only detect antigens when theyare expressed on the surface of antigen-presenting cells (APCs) such as macrophages,certain B-lymphocytes, and dendritic cells (another white blood cell type formed inhaematopoietic stem cells of the red bone marrow). These APCs either engulf anddigest pathogens, or they absorb the antigens which are attached to their receptors,and then display the antigens on their cell surface.

Once activated, the Helper T cells divide rapidly, and then secrete the cytokines whichactivate B-lymphocytes and direct them along with macrophages to the site of theinfection.



The action of T-lymphocytes: Questions

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Q14: What do Cytotoxic T Cells induce to destroy pathogens?

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Q15: How do antigen-presenting cells acquire the antigens which they present?

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Q16: What do Helper T Cells secrete to activate B-lymphocytes?

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Q17: What activates Helper T cells?

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2.5 The action of B-lymphocytes�

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Learning objective


• explain that B-lymphocytes are activated by antigen-presenting cells or T-lymphocytes;

• explain that these activated cells divide repeatedly to produce a clone of B-lymphocytes that secrete antibodies into the lymph and blood, through whichthey make their way to the infected area;

• state that each B-lymphocyte clone produces a specific antibody molecule thatwill recognise a specific antigen surface molecule on a pathogen or a toxin;

• explain that antigen-antibody complexes may inactivate a pathogen or toxin, orrender it more susceptible to phagocytosis;

• state that in other cases the antigen-antibody complex stimulates a responsewhich results in cell lysis.

The activation of B-lymphocytes

B-lymphocytes may be activated in two ways. Antigen-presenting cells, such asmacrophages which have engulfed pathogens, migrate from the site of infection to thelymph nodes, where they display the antigens of the pathogen on their cell membrane.These are transferred directly to the B-lymphocytes there which carry the receptor forthat antigen, so activating them.

Alternatively (and more frequently), T-lymphocytes which have come into contact withthe pathogens carry the foreign antigens, in combination with carrier molecules on theircell surface, to the B-lymphocytes in the lymph nodes. These antigens are likewisetransferred to the receptors of the B-cells and activate them.



The production of antibodies

B-lymphocytes are responsible for the humoral response of the adaptive immunesystem. Their principal function is to produce antibodies specific to particular antigens,although some also act as antigen-presenting cells and develop into memory B cells.Antigens may either be proteins on the surface of pathogens or toxins.

When activated by an antigen binding to their specific receptors, B-lymphocytes dividerepeatedly by mitosis to form a clone of plasma cells. These clones are identical to theparent cells, and so all produce and release large quantities of the antibody which isspecific to the antigen responsible for the initial activation.

The action of antibodies

Antibodies (also known as immunoglobulins) are large Y-shaped protein moleculeswhich are released into the blood, tissue fluid or lymph. If they encounter their targetantigen, they bind to it, forming an antigen-antibody complex.

What follows depends on the actual antigens and pathogens involved:

1. the antibodies cluster around viruses, blocking the sites at which they bind totheir host cells - in a similar fashion, antibodies may bind with bacterial toxinsso rendering them harmless and identifying them to macrophages;

2. antibodies binding to the surface of bacteria may also cause them to clustertogether (agglutinate);

3. some antigens are soluble and circulate in the plasma and lymph - antibodiescause these to precipitate;

4. macrophages patrolling the tissues will be attracted to pathogens and antigenswhich are identified by the antibodies attached to their surfaces, and remove themby phagocytosis;

5. as mentioned in an earlier section, the complement system involves over twentyplasma proteins which act in a cascade to bring about several actions as part ofthe innate immune system. However, the complement systems is also activatedby the binding of antibodies to the antigens of pathogens and other foreign cells(e.g. red blood cells of a different blood group to the host). In this case, their effectis to create pores lined with complement proteins in the pathogen’s cell membrane(known as the ’membrane attack complex’), through which fluid floods into the cellcausing its lysis.



Inflammatory response

The action of B-lymphocytes: Questions

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Q18: Which cells activate B-lymphocytes?

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Q19: Explain what a clone is.

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Q20: When activated, what do B-lymphocytes release?

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Q21: Explain what is meant by the term ’specific’ in relation to antibodies.

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Q22: When an antibody attaches to an antigen, what is formed?

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Q23: How do antibodies de-activate viruses?

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Q24: How do antibodies prepare bacteria for phagocytosis?

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Q25: Explain how antibodies cause the lysis of pathogen cells.

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2.6 Immunological memory�

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Learning objective


• state the some of the cells produced when lymphocytes are activated survivelong-term as memory cells;

• explain that a second exposure to the same antigen stimulates these memorycells rapidly to divide and produce a new clone of lymphocytes;

• state that these new cloned lymphocytes produce a secondary response whichis much more rapid and greater in terms of antibody production.

So far, this topic has described the very efficient way in which the body reacts to invasionby pathogens and foreign antigens. However, the cleverest part of the story remains tobe told: once it has met a particular pathogen or antigen, the immune system is able toremember the foreign antigen signature so that, in any future exposure to that antigen,it can respond so quickly and effectively that the infection is stopped before it can begin.

The formation of memory cells

When an inactive lymphocyte meets the antigen which matches its receptors, it isactivated into rapid cell division. Most of these cloned cells will move to another partof the lymph glands (as plasma cells in the case of B-lymphocytes) or to the site of theinfection (in the case of T-lymphocytes).

A proportion remain behind in the original areas of the lymph nodes where they undergoa selection process which weeds out the cells with the least effective antibodies in termsof fitting the antigen. As a result, by the time the initial infection is brought under control,the antibodies being produced are much more effective than those first released. Thesememory cells are long-lived, and their numbers increase at each re-exposure to theantigen until an optimum level is reached.

Both B- and T-lymphocyte memory cells are found not only in the lymph nodes, but inthe spleen as well where blood is filtered and so can be monitored. In addition, there areT-lymphocyte memory cells which circulate in the blood and so are in constant contactwith the tissues.

The secondary response

When a particular antigen invades the body a second time, the memory cells areactivated very quickly, dividing to form plasma cells and more memory cells, whichare again subject to selection for most effective antibody production. In consequence,the secondary response is much quicker than the primary response and involves muchhigher concentrations of (more effective) antibodies.



Primary and secondary immune responses

A concurrent infection involving a different antigen will not be met with this rapid andmassive production of antibodies. This is because of the specific nature of the antibodyresponse; it only responds to the antigen which activated it. Other antigens have to startat the beginning of the process.

Immunological memory: Questions

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Q26: What is the source of lymphocyte memory cells?

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Q27: State the effect that a second exposure to an antigen has on lymphocyte memorycells.

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Q28: How does the secondary immune response differ from the primary response?

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2.7 Learning points

Summary

Immune surveillance

• The role of white blood cells as constantly monitoring the tissues.

• Pathogens, and other foreign cells or materials, are recognised by theirantigens - molecules on their surfaces that activate the immune system.

• Cytokines are released when tissues are damaged or invaded.

• Cytokines attract specific white blood cells (monocytes) to theinfected/damaged tissue.

• Some of these cells absorb pathogens and display fragments of their cellmembranes on their surface.

Clonal selection theory

• Clonal selection theory explains the way in which lymphocytes aredeveloped to respond to specific antigens which invade the body.

• Lymphocytes have a single type of receptor on the cell membrane which isspecific to one antigen.

• Antigen binding leads to repeated lymphocyte division, which results in aclonal population of lymphocytes.

T- and B-lymphocytes

• Lymphocytes respond specifically to antigens on foreign cells, cells infectedby pathogens and toxins released by pathogens.

• T-lymphocytes have specific surface proteins that allow them to distinguishbetween the surface molecules of the body’s own cells and cells with foreignmolecules on their surface.

• Autoimmune diseases arise as a result of a failure of immune systemregulation, leading to a response by T-lymphocytes to self antigens.

• Activated B-lymphocytes secrete antibodies into the blood and lymph.

• Allergies are a hypersensitive B-lymphocyte response to an antigen that isnormally harmless.

T-lymphocytes

• One group of T-lymphocytes destroys infected cells by inducing apoptosis.

• Another group of T-lymphocytes secrete cytokines that activate B-lymphocytes and phagocytes.

• When pathogens infect tissue, some phagocytes capture the pathogen anddisplay fragments of its antigens on their surface.



Summary continued

• These antigen-presenting cells activate the production of a clone of T-lymphocytes that move to the site of infection under the direction ofcytokines.

B-lymphocytes

• B-lymphocytes are activated by antigen-presenting cells or T-lymphocytes.

• These activated cells divide repeatedly to produce a clone of B-lymphocytesthat secrete antibodies into the lymph and blood, through which they maketheir way to the infected area.

• Each B-lymphocyte clone produces a specific antibody molecule that willrecognise a specific antigen surface molecule on a pathogen or a toxin.

• Antigen-antibody complexes may inactivate a pathogen or toxin, or render itmore susceptible to phagocytosis.

• In other cases the antigen-antibody complex stimulates a response whichresults in cell lysis.

Immunological memory

• Some of the cells produced when lymphocytes are activated survive long-term as memory cells.

• A second exposure to the same antigen stimulates these memory cellsrapidly to divide and produce a new clone of lymphocytes.

• These new cloned lymphocytes produce a secondary response which ismuch more rapid and greater in terms of antibody production.



You should have a good understanding of clonal selection theory before attempting thequestion.


Extended response question: Clonal selection theory

Give an account of clonal selection theory. (6 marks)

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End of Topic 2 test

Go online

Q29: Match the phrases on the left with the words and phrases on the right. (8 marks)

Constantly monitoring the tissues: autoimmune.

Identify pathogens to the immune system: monocytes.

Released by damaged cells: receptors.

Attracted to infected tissues: specific.

Located on the cell membrane of lymphocytes: allergic.

Receptor only binds to one antigen: white blood cells.

A response by T-lymphocytes to the body’s own antigens: cytokines.

A hypersensitive response by B-lymphocytes: antigens.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Q30: Complete the sentences by matching the parts on the left and the right. (7 marks)

T-lymphocytes destroy infected cells by inducing T-lymphocytes.

T-lymphocytes secrete cytokines that activate a clone of T-lymphocytes.

Antigen-presenting cells activate the production ofan antigen-antibodycomplex.

B-lymphocytes are activated by antigen-presenting phagocytosis.

Each B-lymphocyte clone produces B-lymphocytes.

Antigen-antibody complexes render pathogenssusceptible to

apoptosis.

Cell lysis is a response stimulated by a specific antibodymolecule.

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Q31: Explain how T-lymphocytes identify pathogens. (2 marks)

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Q32: Describe what happens after B-lymphocytes are activated. (2 marks)

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Q33: Explain why the secondary response to a pathogen is more effective than theprimary response. (2 marks)

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35

Topic 3

The transmission and control ofinfectious diseases

Contents

3.1 Infectious diseases caused by pathogens . . . . . . . . . . . . . . . . . . . . . 36

3.2 Methods of transmission of pathogens . . . . . . . . . . . . . . . . . . . . . . 42

3.3 Control of spread of pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . 44

3.4 Epidemiological studies of infectious diseases . . . . . . . . . . . . . . . . . . 49

3.4.1 Epidemiology and the spread of disease . . . . . . . . . . . . . . . . . . 49

3.4.2 Control measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

3.5 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53


3.7 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

Learning objectives


• describe the nature of pathogens and disease;

• describe the ways in which pathogens may be transmitted;

• describe the methods by which the spread of pathogens may be controlled;

• list the different degrees of spread of infectious diseases;

• explain the measures which can be taken to control the spread of a disease withina population.

36 TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES

In the previous topics of this unit, the body’s immune defences, both specific and non-specific, were described. In this topic, the focus is on the ways in which diseases spreadthrough populations and the means by which they may be controlled.

3.1 Infectious diseases caused by pathogens�

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Learning objective


• list the types of infectious agent that cause disease;

• name an example of a disease caused by each type of pathogen.

Pathogen is a very broad term which encompasses anything that can produce diseasein its host. It is generally used to refer to some sort of micro-organism, and includesviruses, bacteria, fungi, protozoans, and even the misfolded proteins that are prions.Excluded are carcinogens, for example blue asbsestos (crocodilite), and neurotoxins,such as that produced by the bacterium Clostridium botulinum.

Pathogens are, of course, just trying to make a living like any other organism; theproblem lies in that they use us as their habitat and source of nutrition, causing ourbodies damage in the process. It should be remembered that on our body surfaces, inour intestinal tract, and within our tissues we harbour huge numbers of micro-organismswhich do us no harm or, indeed, are extremely beneficial to us.

The term disease also needs definition as a condition in which the body malfunctionsin some way; in this topic, we are concerned only with diseases which are caused bypathogens, rather than inherited, psychological or deficiency diseases. New diseasesare discovered every year, with more than 30 being described in the last 20 years.Estimates of the total number of human diseases vary considerably, although somethingin excess of 30,000 is a common suggestion.


TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES 37

Viruses

Bird flu virushttp://blog.patentology.com.au/2011/11/shades-of-gray-as-dispute-over.html (https://plus.google.com/116299882295651429004/about) / http://creativecommons.org/licenses

/by-nc-sa/3.0/au/

Most viruses have a diameter of between 20 and 300nm (nanometres, 10 -9m). Allconsist of a protein coat containing a molecule of nucleic acid (RNA or, more rarely,DNA), but they lack any other cellular organelles and are consequently dependent onother cells for their reproduction. They are found in all other life-forms.

Diseases caused by viruses range in severity from mild infections such as the commoncold and herpes (cold-sores) to those with very high mortality rates such as smallpoxand ebola.


http://blog.patentology.com.au/2011/11/shades-of-gray-as-dispute-over.html

https://plus.google.com/116299882295651429004/about

https://plus.google.com/116299882295651429004/about

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http://creativecommons.org/licenses/by-nc-sa/3.0/au/


Bacteria

Escherichia coli

A bacterium is typically between 0.5 and 5.0µm (micrometres, 10-6m) in length. Theyhave a cell membrane inside a cell wall, but lack any membrane-enclosed organellessuch as a nucleus.

However, their cytoplasm is organised by a cytoskeleton of structural proteins andcontains ribosomes. Their genes are carried on a single circular chromosome of DNA,and on smaller DNA plasmids.

Diseases caused by bacteria include tetanus, typhoid fever, diphtheria, syphilis, cholera,salmonella, pneumonia, meningitis and tuberculosis.



Fungi

Athlete’s foot fungus in lab culture(http://commons.wikimedia.org/wiki/Category:Athlete%27s_foot#mediaviewer/File:Athlete%27s_Foot_Fungus_microscope.jpg by Ecorahul, licensed under http://creativecom

mons.org/licenses/by-sa/3.0 via http://commons.wikimedia.org/)

Comprised of a cell wall made of chitin (the same protein as makes up insectexoskeletons), cytoplasm with organelles, and a nucleus with chromosomes, most fungiexist as long filaments of cells called hyphae which are typically 5µm wide; some arefound as single cells (e.g. yeast).

Relatively few fungi cause diseases in humans, but they can lead to seriouscomplications in certain situations. Those that people are most likely to be familiarwith are the mild, if annoying, infections such as athlete’s foot and thrush. However, thelatter shows just how these microbes can cause serious problems if they gain entry tothe deeper body tissues. If the Candida yeast (which causes thrush) invades the tissuesafter a transplant operation for which the patient’s immune system has been suppressed,the result can be systemic candidiasis, which has a mortality rate of up to 50%.


http://commons.wikimedia.org/wiki/Category:Athlete%27s_foot#mediaviewer/File:Athlete%27s_Foot_Fungus_microscope.jpg

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Protozoans

Plasmodium, (about 12µm long) the protozoan causing malaria, among host’s redblood cells

In many ways, the members of this very diverse group of organisms resemble free-livinganimal cells, in that they have a cell membrane, nucleus and organelles. Diseasescaused by protozoans include: several involving insect vectors as alternate hosts, e.g.malaria, Chagas disease, sleeping sickness; toxoplasmosis, with cats as an alternatehost; and amoebic dysentery, which is spread through faecal contamination of food orwater.



Prions

Cow brain tissue, showing the microscopic holes typical of bovine spongiformencephalopathy (BSE)

Prions are not organisms but a type of misfolded protein which appear to be passedfrom host to host by consumption of infected tissue. They are thought to cause proteinto alter and accumulate in the host’s brain and other neural tissue, a change whichis untreatable and ultimately fatal. Examples are kuru and Creuztfeldt-Jakob Disease(CJD). Their size is a matter of speculation, but one estimate is about 10nm.

Infectious diseases caused by pathogens: Question

Go online

Q1: Complete the following table to show the types of organism that are pathogensand examples of the infectious diseases which they cause.

Type of pathogen Example of disease

Pathogens and diseases: bacteria, candidiasis, CJD, fungi, herpes, malaria,pneumonia, prion, protozoa, virus.

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3.2 Methods of transmission of pathogens�

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Learning objective


• explain that pathogens may be transmitted by direct physical contact, water,food, body fluids, inhaled air or vector organisms.

Pathogens which cause infectious diseases are very sensitive to their environments.They only have the ability to survive and multiply if there is the availability of correctnutrients and the right environmental conditions. Some microbes such as bacteria,for example, require an optimum temperature range (20 to 40◦C), sufficient moisture,correct pH and oxygen levels. However, some bacterial spores can survive extremeenvironmental conditions.

The transmission of an infectious disease is the passing on of a pathogen from aninfected host individual to another individual by one or more of the following methods:

• physical contact (contagious diseases)

◦ direct physical contact takes place by touch, like a handshake or sexualcontact - even though the skin is host to many microbes, the majorityof these are benign unless they gain access to the internal organs; themost common bacteria found on the skin that can cause infection areStaphalococcus and Streptococcus, and the most notorious is methycillin-resistant Staphalococcus aureus (MRSA);

◦ indirect physical contact usually takes place by touching contaminatedsurfaces, like a door handle or floor - free living microbes, such as bacteriaand fungi, can survive on non-living objects longer than viruses; Rhinoviruses(cold) and gastroenteritis can be spread in this manner, as can somepathogenic fungi such as the Trychophyton species which cause athlete’sfoot

• water-borne diseases are most often spread via drinking water that has beencontaminated with human or animal faeces; this is the faecal-oral infection route- in Economically Less Developed Countries, four-fifths of all the illnesses arecaused by water-borne pathogens, with diarrhoea caused by cholera or dysenterybeing the leading cause of child mortality;

• food-borne diseases, of which there are over 250, are caused by a variety ofbacteria, viruses, and parasites - they usually result from poor personal hygiene,poor hygiene in food preparation, or in the food material supply chain; diseasescaused by food-borne organisms include: cholera, rotavirus, shigellosis (bacillarydysentery), typhoid fever, hepatitis A and hepatitis E;

• body fluids - a healthy person who gets infected mucus into their eyes, nose,or mouth can become infected with certain diseases that are spread in theblood or which grow in the flesh around a wound where the body may producepus (a viscous, yellowish-white fluid that is formed in infected tissues mainlyfrom white blood cells), e.g. hepatitis (in its several forms); some diseases arecaused by microbes which are carried in the fluids exchanged during sexual



relations, e.g. HIV (human immunodeficiency virus) which causes AIDS (acquiredimmunodeficiency syndrome);

• air-borne transmission occurs when microbes are attached to droplets of moisturein the air (e.g. from a sneeze) or to dust particles that are inhaled - such microbescan travel long distances before they are inhaled by other people, e.g. the measlesvirus, bacteria such as Mycobacterium tuberculosis (TB), and Bacillus anthracis(anthrax);

• vector organisms provide a pathway for a pathogen to be transmitted betweenanimals and humans or other animals, with some vector organisms providing thistransport by blood-sucking - the vectors are largely unaffected by the pathogen,thus allowing for the successful transport of the disease. According to WHO,the most deadly vector-borne disease is Malaria, killing over 1.2 million peopleannually, mostly African children under the age of five. Another vector-bornedisease is dengue fever (DF), a viral disease also spread by mosquitoes. Togetherwith associated dengue haemorrhagic fever (DHF), DF is the world’s fastestgrowing vector-borne disease. In Britain, Lyme disease is of increasing concern;it is caused by bacteria of the Borelia genus and is spread by ticks when they takea blood meal on a human, dog, or other mammals such as deer.

Methods of transmission of pathogens: Question

Go online

Q2: Complete the following table to show the types of organism that are pathogensand examples of the infectious diseases which they cause.

Method of transmission Example of disease

Methods of transmission and diseases: body fluids, dengue fever, direct physicalcontact, dysentery, food, gastroenteritis, HIV, indirect physical contact, inhaled air,measles, MRSA, typhoid, vectors, water.

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3.3 Control of spread of pathogens�

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Learning objective


• state that the spread of pathogens can be controlled by quarantine andantisepsis;

• explain the role of individual responsibility by means of good hygiene, care insexual health, and appropriate storage/handling of food;

• describe the role of community responsibility by means of quality of watersupply, safe food webs, and appropriate waste disposal systems;

• explain the role of vector control in reducing the spread of pathogens.

Quarantine

Quarantine controls the spread of an infectious disease by keeping potentially infectedindividuals, i.e. those who may have been exposed to the disease, apart from theremainder of the population. Persons who are known to be ill with a contagious diseaseare isolated from all others.

The Apollo 11 astronauts are quarantined following their return to Earth



During the global outbreak of SARS (severe acute respiratory syndrome) in 2003,public health officials introduced measures aimed at controlling its spread in affectedareas. Initially, this was done by alerting health-care providers and providing them withdiagnostic protocols. Many of the SARS cases were quickly identified. However, it wassoon recognised that the disease had spread at a much greater rate than was initiallythought. As a result, several countries/regions introduced the use of mass quarantinefor all individuals suspected of having had contact with a confirmed SARS case. Thesecoordinated global efforts were remarkably effective in controlling the spread of SARSand, to date, the disease has not made a significant re-emergence.

Modern quarantine lasts only as long as necessary to protect the public by providinghealth care, such as immunisation or drug treatment. Nowadays, quarantine is morelikely to involve limited numbers of exposed persons in small areas rather large numbersin whole neighbourhoods or cities.

Antisepsis

Antiseptics are chemicals which are applied to skin or living tissue to reduce thepossibility of transmission of pathogens, and to counter the infection of healthy tissue, orthe decomposition of dead or damaged tissue. They act against microbes by disruptingcell structures including: cell wall/membrane, internal membranes, protein structures,DNA and RNA. In so doing, antiseptics also either kill the pathogens or inhibit theirgrowth and reproduction.

Hand washing is at once the simplest and yet one of the most effective techniques.Decontamination of the hands can be achieved either with plain soap and water, or byuse of an antiseptic hand gel. The use of soap is important as it helps lipids dissolve andso dislodges bacteria held in natural skin oils. Although it does not counter the spreadof droplet-borne infections, hand washing is very effective against pathogens spread bythe faecal-oral route. Therefore, hand washing is very important after using the toilet,touching raw food, changing a baby’s nappies, cleaning up after a pet, or removingrubbish bins.

Disinfectants are also antimicrobial agents which work by destroying the cell wall ofpathogens or by interfering with their metabolism. They are used on non-living surfacessuch as food preparation areas in the domestic kitchen or commercial premises such asbutcher’s shops, restaurants, and of course in hospitals.

Individual responsibility

An individual’s personal behaviour can have a considerable impact on the control andprevention of the spread of disease. This applies not just to the health of their ownimmediate household, but collectively it contributes greatly to community health.

Emphasis should be placed on an individual’s responsibility to:

• provide good hygiene both personally and within the home;

• be sensitive to oneself and to others in matters of sexual health;

• take care over the appropriate handling and storage of food.



Community responsibility

Once humans ceased to be hunter-gatherers and started to live in groups larger thana family, there had to be a division of labour, and we began to depend on the others inthe community to carry out certain key tasks for us. Today, few of us kill and butcher ourown meat, or have our own private water supply. In Britain we expect our rubbish to becollected and only country-dwellers rely on a septic tank to process their sewage.

The most fundamental of community responsibilities is the provision of clean, safe(potable) drinking water. This can only be assured if contamination by sewage isprevented by ensuring that waste water and drinking water cannot mix. To achieve this,we have sewerage systems to remove waste water and our drinking water is taken from(relatively) uncontaminated sources, filtered, purified to remove dangerous chemicals,and disinfected to eliminate most bacteria. It is interesting that in Britain we wash ourcars, water the garden and flush our toilets with water of drinking quality when potablewater is a scarce and valuable resource to much of the world’s population.

Waste water treatment works

The other side of the coin to the provision of potable water is the provision of effectivesanitation. This requires not just the clear separation of sewage from drinking water,but the disposal of sewage in such way that it cannot contaminate cooking, washing orbathing water, or indeed the water children swim in. We should remember that only fiftyyears ago, Scottish coastal towns were still pouring raw sewage straight into the sea,often close to bathing beaches.

Over one-third of the world’s population, nearly 2.5 billion people, have inadequateaccess to sanitation, and over one billion people do not have access to enough safewater. These conditions, combined with poor hygiene, are largely responsible for thefact that there are globally between 1.7 and 5 billion cases of diarrhoea annually (e.g.typhoid, cholera, dysentery). Of those affected, about three million die each year.



Community responsibility can reduce the number of cases of diseases, and actions mayinclude:

• access to safe drinking water;

• improved sanitation;

• supervision of food chains, by insisting on minimum standards of hygiene, e.g. inabattoirs, restaurants, fast-food outlets, supermarkets, market stalls;

• health education of all age-groups, especially children, parents and the elderly.

Control of vectors

Most vector organisms are blood-sucking arthropods, particularly insects andarachnids (ticks). The relationship between the pathogen and its hosts is one that hasevolved over a long time because the pathogens can often only complete their life cycleif they have access to a different host species at each stage.

On a global scale, the Anopheles mosquitoes which spread malaria are the mostimportant insect vectors. They carry the Plasmodium protozoan, which passes part of itslife-cycle in the mosquito as its primary host, but must then be transferred to a mammalsuch as a human as a secondary host to complete its life cycle. For the disease tospread, the pathogen must be again taken into a mosquito in a blood meal.

Female Anopheles mosquito feeding

The most effective way to combat the disease is to limit the available habitat for the larvalstages of the mosquito, which means removing the stagnant water in which the eggsare laid, for example that collected in old tyres. Other techniques include: the sterilemale technique, in which large quantities of laboratory-bred sterile male mosquitoes arereleased, and the introduction of fish which eat the mosquito larvae. In Britain, fivespecies of Anopheles are found (three in Scotland), but since most of the marshlandin the country has long since been drained, malaria died out several centuries ago.



Insecticides have also been used, but as with antibiotics, over-use and misuse have ledto the development of resistant varieties.

In Scotland, Ixodes ricinus (sheep tick) spreads Borrelia bacteria which cause Lymedisease. The bacteria are passed between the tick and two types of mammal host.Unlike the mosquitoes, where only mature females take a blood meal, all ticks of allsizes feed on blood.

Sheep ticks mating (the larger size of the female gives an idea of the size that a malewould grow to after feeding)

In the earliest stages of the life cycle, ticks prefer mice as their hosts (although they willattach to any available food source), and can only pick up Borrelia from them. In the finalstage, ticks prefer large mammals, such as deer, foxes or sheep (or humans), to whomthey can transfer the bacteria, but from whom none of the stages can get the bacteria.

In the context of the increasing occurrence of large wild mammals in and aroundurban areas, and the growing use of forests for recreation, ticks pose a serious healthrisk which is not widely appreciated. The obvious vector control measure of severelyreducing deer and fox populations is likely to be controversial.

Control of spread of pathogens: Questions

Go online

Q3: Describe how the spread of pathogens is controlled by quarantine.

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Q4: Describe how the spread of pathogens is controlled by antisepsis.

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Q5: List the ways in which individuals should take responsibility for the control of thespread of pathogens.



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Q6: State the areas of control of pathogens that are the responsibility of communitiesin More Economically Developed Countries.

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Q7: Explain the role of vector control in reducing the spread of pathogens.

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3.4 Epidemiological studies of infectious diseases�

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Learning objective


• state that epidemiology is the study of the causes and patterns of spread ofdisease;

• describe the patterns of disease spread as:

◦ sporadic (occasional occurrence);

◦ endemic (regular cases occurring in an area);

◦ epidemic (unusually high number of cases in an area);

◦ pandemic (a global epidemic).

• describe control measures to include preventing transmission, drug therapy,immunisation or a combination of these.

3.4.1 Epidemiology and the spread of disease

Epidemiology is the study of the causes and patterns of spread of disease. As such, itunderpins public health decisions, provides the foundation for the development of policyand the direction of research.

At different times and places, diseases show different patterns of spread.

Sporadic

In an age of global travel, it is inevitable that an infected person will arrive in a countryand develop a disease which is not normally present in that area. If the local populationare mostly vaccinated against that disease, or no vector species exists, then thepathogen will be unable to find an alternative host before the patient’s immune systemeradicates it, and so it dies out in that area.

An example would be malaria in Britain. Every year people arrive in the countrycarrying the Plasmodium protozoan in their blood, but as the Anopheles mosquitoes arerestricted to very specific uncommon habitats, the disease is usually unable to spreadbefore the patient is treated and the pathogen eliminated.



Endemic

An infection is said to be endemic when that infection is maintained in the populationwithout the need for external inputs. For example, rubella and the common coldrhinovirus are endemic in Britain, but malaria is not. To maintain this steady state, thepathogen must be able to find new hosts sufficiently frequently to avoid extinction, butnot so often that the number of cases begins to increase significantly. This equilibriumdepends on the relationship between the number of new cases that one infected personcan generate before their infectious period is over (as their immune system controls theinfection), and the number of susceptible people in the population.

Epidemic

An epidemic occurs when the number of cases of a disease increases significantlyabove that normally recorded. For this to happen, the equilibrium of the endemicstate must be disturbed in some way. It might, of course, also be the result of somenew pathogen arriving, against which the immune systems of the population give noimmediate protection.

Every winter in Scotland, susceptible individuals (over 65, pregnant women, thosewith particular health conditions, pre-school and primary school children) are offeredan injection of the flu vaccine which counters the strains of Influenzavirus which areexpected in the coming flu season. This is always something of a gamble, as theflu virus mutates frequently and the health authorities have to judge which strains willpredominate in any winter.

Pandemic

When a disease reaches epidemic proportions in many different countries, it is classedas a pandemic. Modern air transport links make the potential for the global spread ofa disease much greater, but this is countered by a much deeper understanding of thebehaviour of diseases and more sophisticated methods of tracing potentially infectedindividuals. Thus, while the swine flu pandemic of 2009 killed roughly 18,000 people,the Spanish flu pandemic of 1918 is estimated to have killed between 20 and 100 million.Both of these outbreaks involved the H1N1 variant of the type A Influenzavirus.

Epidemiology and the spread of disease: Question

Go online

Q8: Match the phrases on the left with the words on the right.

The disease occurs occasionally in a population: endemic.

Cases of the disease occur regularly in an area: pandemic.

There are unusually high numbers of cases in an area: sporadic.

Unusually high numbers of cases in many countries: epidemic.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .



3.4.2 Control measures

When an outbreak of disease is anticipated or has already begun, there are a numberof strategies that health authorities can adopt to control the outbreak and reduce thepossibility of it reaching epidemic or pandemic proportions. These may be applied singlyor in combination.

Preventing transmission

If a disease outbreak has already begun, infected individuals can be isolated andknown contacts quarantined. The media can be used to inform the public of symptoms,and information can be gathered by communication with travel companies, immigrationofficials, business contacts and others who might have knowledge of an infectedperson’s movements. Airport officials can be alerted so that passengers on flights fromparticular countries can be screened and alerted to the symptoms.

An extreme case involves the Ebola virus, which sporadically erupts in West Africa.This is an example of a pathogen that transfers to humans from other animals, in thiscase mainly fruit bats. As is typical of a pathogen that is not adapted to a new host,Ebola rapidly kills most of the patients it infects. It is also highly contagious, spreadingquickly from human to human in a population. The standard approach to containing suchan outbreak is to isolate the community, give such medical relief as is possible (thereis no cure), and wait until the survivors are no longer infectious (about two months).Interestingly, the rate of mortality amongst patients is much higher early in an outbreakthan towards the end, indicating that the selection pressure on the virus in the course ofthe outbreak favours less virulent strains.

Drug therapy

Once an outbreak is under way, people who are infected may be treated in a number ofways to combat the disease or ameliorate the symptoms.

The most frequent treatment is some form of antibiotic. These are chemicals that arenaturally produced by fungi or bacteria to impede the growth of competing microbes,penicillin being the famous first example to be discovered. Today, most antibiotics aremanufactured synthetically, although some still involve an element of biosynthesis, e.g.streptomycin. Broad spectrum antibiotics target a wide range of bacteria, whereasnarrow spectrum antibiotics act against specific types of bacteria. Antibiotics affectbacteria in a wide range of different ways. Some attack the bacterial cell wall or cellmembrane, others interfere with essential enzymes or with protein synthesis.

Antibiotics only work against bacteria; other types of drugs that are used as bactericidesare sulphonamides and quinolones. Viruses are addressed with antiviral drugs thattarget particular viral proteins which are as different as possible from any found in thehuman body. These attack the virus at different stages in its life cycle:

• before it enters the cell, e.g. pleconaril, which is used against the common coldRhinovirus, and the virus causing meningitis;

• during viral synthesis, e.g. zidovudine (AZT) countering HIV, and so-called’antisense’ antivirals against dengue fever;

• at the release phase from the cell, e.g. Relenza and Tamiflu used against flu.



Another approach to counter viruses is to stimulate the immune system, e.g. interferonused against hepatitis B and C.

All of these drugs are subject to the development of drug resistance, as exposure of themicrobes to the drug exerts strong selection pressure in favour of those bacteria andviruses less seriously affected by the drug.

Individuals who have been exposed to infection may be injected with antibodies toprovide passive immunity to a disease. This may be used to counter tetanus, rabies,rubella, hepatitis A and B.

Immunisation

The theory of immunisation is covered in the next topic. By exposing a person to thesurface proteins (antigens) of a pathogen (usually by injection), their immune systemwill be stimulated to develop the lymphocyte memory cells necessary to initiate arapid, strong secondary response if the pathogen itself is encountered. This is theprinciple behind the provision of annual winter flu injections and the MMR, TB andtetanus vaccination programmes. Clearly, immunisation is not a treatment for thosealready infected, and it does depend on an informed guess as to exactly which strainsof pathogen are likely to be encountered.

Control measures: Questions

Go onlineQ9: What is the most suitable treatment for a person who has flu caused by the H1N1virus?

a) Antibioticsb) Immunisationc) Isolation

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Q10: Long-term resistance to tetanus is achieved by:

a) Antibioticsb) Antiviralsc) Immunisation

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Q11: A person who has contracted the bacterial infection tetanus should be treatedwith:

a) Antibioticsb) Antibodiesc) Antivirals

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3.5 Learning points

Summary

Methods of transmission of pathogens

• Pathogens may be transmitted by direct physical contact, water, food, bodyfluids, inhaled air or vector organisms.

Control of spread of pathogens

• The spread of pathogens can be controlled by quarantine and antisepsis.

• The role of individual responsibility by means of good hygiene, care insexual health and appropriate storage/handling of food.

• The role of community responsibility by means of quality of water supply,safe food webs, and appropriate waste disposal systems.

• The role of vector control in reducing the spread of pathogens.

Epidemiological studies of infectious diseases

• Epidemiology is the study of the causes and patterns of spread of disease.

• The patterns of spread of disease are:

◦ sporadic (occasional occurrence);

◦ endemic (regular cases occurring in an area);

◦ epidemic (unusually high number of cases in an area);

◦ pandemic (a global epidemic).

• Control measures include preventing transmission, drug therapy,immunisation or a combination of these.



You should have a good understanding of the control of spread of pathogens beforeattempting the question.


Extended response question: Control of spread of pathogens

Describe the role of community responsibility in the control of the spread of pathogens.(6 marks)

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End of Topic 3 test

Go online

Q12: Complete the paragraph by selecting words from the list. Some words may beused more than once. (12 marks)

Pathogens may be transmitted by direct �� contact, water, ��, body fluids,inhaled �� or �� organisms. The spread of pathogens can be controlled byquarantine and ��.

Individuals have a responsibility to control disease by means of good ��, carein �� health and appropriate storage/�� of food. The role of community isto ensure the quality of �� supply, safe food ��, and appropriate ��

disposal systems. Communities may also reduce the spread of disease by means ofprogrammes of �� control.

Word list : air, antisepsis, food, handling, hygiene, physical, sexual, vector, waste, water,webs.

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Q13: Explain how quarantine helps control the spread of disease. (2 marks)

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Q14: State two ways in which health authorities ensure drinking water is safe. (2 marks)

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Q15: Name a vector-borne disease and state one way in which its spread may becontrolled. (2 marks)

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Q16: What is an endemic disease? (1 mark)

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Q17: Explain how an endemic disease, e.g. flu, can become an epidemic. (1 mark)

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55

Topic 4

Active immunisation

Contents

4.1 Active immunisation and vaccination . . . . . . . . . . . . . . . . . . . . . . . 56

4.1.1 Active immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

4.1.2 Vaccine clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

4.2 Herd Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

4.3 Immunisation programmes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

4.4 The evasion of specific immune responses by pathogens . . . . . . . . . . . . 70

4.4.1 Antigenic variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

4.4.2 Antigenic variation in different pathogens . . . . . . . . . . . . . . . . . 72

4.4.3 Direct attack on the immune system . . . . . . . . . . . . . . . . . . . . 75

4.4.4 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

4.5 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78


4.7 End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Learning objectives


• describe the development of active immunisation;

• explain the purpose of vaccinations, the development of vaccines and associatedpublic health programmes;

• describe the way in which some pathogens evade the specific immune response.

56 TOPIC 4. ACTIVE IMMUNISATION

4.1 Active immunisation and vaccination

An individual will develop an immunological memory (Topic 2.6) against a foreign antigenas a result of exposure to that antigen. This may be caused by natural exposure to theantigen, e.g. by contracting the disease, which was the way children in Britain becameimmune to measles, mumps and rubella before 1988. Alternatively, an injection ofvaccine containing the antigen can be given to stimulate the development of artificialimmunity. Since 1988, all British children have been offered such artificial immunisationbefore their first birthday as part of their routine vaccination schedule.

The first well-documented use of artificial immunisation was in China in the 16th century,and the practice was recorded from India, Africa and Turkey in the 18th century at aboutthe same time that it began to be practised in Britain and other countries of westernEurope. The disease involved was smallpox, which can kill up to 60% of those infected(and up to 80% of children under five years of age). The technique was inoculation, inwhich scabs taken from an infected person were introduced (either whole or powdered)into an incision on the arm of an uninfected person. Surprisingly, perhaps, rather thanpromptly killing a high proportion of the patients, this technique caused a relatively mildinfection which had the desired effect of protecting them in subsequent exposures to thedisease. It did, however, depend on the presence of the disease in the community forthe necessary supply of scabs.

The process of using a source of antigens other than the pathogen itself was firstintroduced by Edward Jenner (and others) in the late 18th century. He used pus fromscabs caused by cowpox to inoculate patients who later proved to be immune to themuch more serious and related disease smallpox. Nearly a century later, the procedurewas significantly refined by Louis Pasteur. Because of the early use of cowpox in theprocess, the treatment was called vaccination (vacca is Latin for cow).

Although the terms vaccination and inoculation are now often used interchangeably,strictly speaking vaccination refers to the use of some weakened form of a pathogen,whereas inoculation uses the real thing (and is consequently a much more dangerousbusiness). Inoculation is also the term used for the addition of a culture of microbesto a growth medium in the lab. There is no doubt that vaccination is the single mostimportant discovery in the control of disease. Without it, serious diseases such as polioand smallpox would still be claiming millions of lives around the planet every year.


TOPIC 4. ACTIVE IMMUNISATION 57

4.1.1 Active immunity�

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Learning objective


• state that active immunity can be developed by vaccination with antigens frominfectious pathogens;

• explain that vaccination creates an immunological memory;

• state that vaccines include antigens from infectious pathogens, includinginactivated pathogen toxins, dead pathogens, parts of pathogens and weakenedpathogens;

• state that the antigens in vaccines are usually mixed with an adjuvant toenhance the immune response.

Immunity against a pathogen can be developed in a number of ways. Mostfundamentally, immunity may either be active or passive:

• active immunity involves the development of immunological memory, either asa result of exposure to the pathogen’s antigens (naturally acquired) or throughexposure to the same antigens in a vaccination (artificially acquired);

• passive immunity involves the acquisition of antibodies, either naturally acrossthe placenta or from breast milk, or artificially through an injection (e.g. in thetreatment of rabies).

Of these, only the development of artificial active immunity by means of vaccinationprogrammes is of practical importance, although the valuable role of breast feeding inprotecting infants should also be stressed in the course of antenatal classes.

Vaccination

Vaccination is the deliberate introduction of pathogen antigens into the body, usually byinjection but, in some cases, orally or nasally. Exposure to the antigen induces a primaryresponse from the adaptive immune system, in particular leading to the development ofan immunological memory in the form of memory B- and T-lymphocytes. In a second orsubsequent exposure to the same antigen, a secondary response is triggered. As soonas the antigen is detected, memory cells begin rapid division to generate large numbersof B-lymphocyte plasma cells. These cells release their antibodies into the circulation,leading to such a quick build up of antibodies that the invading pathogen is neutralisedbefore it can cause any harm. However, while vaccination greatly reduces the chanceof infection, it cannot entirely eliminate it.



Primary and secondard responses after vaccination

Adjuvants

In addition to the antigenic ingredient, vaccines contain chemicals which act to modifythe immune response engendered by the vaccine, either by increasing the production ofantibodies or by making the protection provided last longer, or sometimes only activatingT-lymphocytes. The most commonly used adjuvant is alum (potassium aluminiumsulphate), although several other substances may be used including paraffin oil andbacterial products.

Antigens

There are a variety of sources used to provide the essential antigens in a vaccine.

• Live attenuated microbes - these contain the same antigens as the pathogen,but the microbes have been sub-cultured many times in the laboratory so that theybecome an ’attenuated’ strain, i.e. they can no longer cause the full-blown disease,although they may cause a very mild form of it. The first vaccine, the smallpoxvaccine, consisted of a live attenuated virus. The MMR (measles, mumps andrubella) vaccine falls into this category.

• Toxoid - these are inactivated toxins; vaccines include Diphtheria and tetanus (partof DTaP combined immunisation).

• Dead pathogens - the microbes are destroyed by heat and chemicals although thedead pathogen still carries the antigens which stimulate the immune response;vaccines for Hepatitis A, polio and cholera fall into this category.

• A fragment of a pathogen - the viral coat component can be used as a vaccine;the HPV vaccine has the viral protein coat protein of the Human Papilloma Virus,as does the vaccine for Hepatitis B.



Administration of vaccines

Vaccines are most commonly administered by injection, although some are given as anasal spray or by mouth. Inhaled (nasal) vaccine can be used against influenza andingested (oral) vaccines for protection against polio.

New techniques of vaccine administration include a patch application, in which a patchcontaining a matrix of extremely tiny needles delivers a vaccine without the use of asyringe. This method of delivery could be particularly useful in remote areas becauseits application would not require delivery by a trained medical person.

Active immunity: Questions

Go online

Q1: Complete the following table concerning vaccines using the words and phrasesfrom the list.

Component Function

Word and phrase list : adjuvant, antigen, creates immunological memory, enhancesimmune response.

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Q2: State the four different sources of antigen found in vaccines.

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4.1.2 Vaccine clinical trials�

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Learning objective


• describe key aspects of the protocol for any vaccine clinical trial as being thatthe trial should be:

◦ randomised;

◦ double-blind;

◦ placebo-controlled;

• explain the importance of group size in reducing experimental error andincreasing statistical significance.

Vaccine Clinical Trials

Before a licence can be issued for a vaccine or a drug to be administered to the public,it must be subjected to an intensive series of trials to establish its safety and efficacy.

In advance of any human trials, the vaccine must undergo extensive laboratory research,including tests on cell cultures and laboratory animals. These pre-clinical trials allowvaccine researchers to gain a better understanding of how the treatment works and ofany side effects. A new cancer drug can take up to six years of testing in the laboratorybefore it reaches the clinical trials stage. Even then, very few drugs get to the clinical



trials; only one in every one thousand new drugs reaches the clinical trials.

The next step is to seek approval from the regulatory authority of the member statein which the trial is to be conducted. In the UK, this is the Medicines and Healthcareproducts Regulatory Agency (MHRA).

Protocols must be drawn up at this stage for the trials, these may include:

• target groups for the trials;

• number of subjects involved in these trials;

• other treatments with which to be compared;

• procedures for collection and interpretation of data.

The protocol will now undergo independent scientific review and, at the same time, itmust be approved by the ethics committee. These steps are intended to ensure that thetrial is foolproof and will respect rights, dignity, safety and well-being of the subjects.

In the UK, all clinical trials have to meet the standard set by the European Union ClinicalTrials Directive. The process ensures all trials are carried out to the same standardwherever they take place in Europe. The process for clinical trials is summarised below.

Summary of clinical trial protocols

A protocol is a predefined procedure for conducting a scientific investigation which willallow the method to be standardised so that the study can be repeated exactly. The keyfeatures of a vaccine clinical trial protocol are that the procedure should be:

• randomised - all subjects in the trial should have an equal chance of being givenvaccine or the placebo, usually done by allocating individuals to treatments usingsome kind of random-number generator;

• double-blind - neither the subjects nor the persons carrying out the trial knowwhich subjects are getting the vaccine and which the placebo;

• placebo-controlled - the trial subjects are divided into two groups, one receivingthe vaccine and the other receiving the placebo, a treatment which is similar in allrespects to the vaccine apart from the active ingredient being tested.



The importance of group size

By this stage in their science studies, all students should be aware that increasing thenumber of individuals in a study, or repeating the investigation, will make the results morereliable. However, few are usually able to explain why this is so. Before addressing this,a few key concepts need to be defined.

Sample

Rarely is it possible to study all the individuals in the population being investigated. Evenin a general election, not all of the people eligible to vote actually do so; in fact, those whovote are a self-selected group who may not at all represent the views of those who do notvote. A scientist might approach the challenge of ensuring fair representation differently.Firstly, not all individuals need be consulted. Rather a much smaller representativegroup would be selected for study; that is the sample.

This sample would be selected randomly, i.e. everyone in the population would have anequal chance of being included. The population would be divided up into different socio-economic and geographical groupings, and the number of people chosen from eachgrouping would be in proportion to the size of this grouping in the whole population.This would ensure that all groups are represented in the sample, and no one group hasa disproportionate influence.

Of course, general elections will never be run this way, as ’one person, one vote’ is afundamental principal of democracy, but it is exactly the way in which national opinionpolls are run.

True values versus sample estimates

Imagine being asked to estimate the mean height of boys in the second year of thelocal high school, but only being allowed enough time to measure thirty of them. If theboys are selected randomly, with all having an equal chance of being in the sample, themean calculated from this group would be representative of the year group. However,that sample mean is very unlikely to be same value as the one that would have beenachieved if every boy had indeed been measured to find the true value.

A key task in sampling is to ensure that the estimate value derived from a sample isacceptably close to the true value, and this is increasingly likely as the sample size isincreased.

Experimental error

This is not to do with mistakes, although these do of course get made e.g. misreadingscales, omitting numbers. Such blunders usually stand out and should be excluded fromany analysis.

Experimental error is any deviation of the measured value from the true value. It isinherent in any technique, although efforts are always made to minimise it. Supposea simple task of weighing out chemicals is required. First of all the balance must beproperly zeroed and operated at the correct voltage and temperature; these sources oferror can be minimised.

However, if the balance only measures to 1g, then if the reading is 10g, the balanceis really saying that the sample weighs somewhere between 9.50g and 10.49g (to twodecimal places). This source of error is a function of the apparatus used, and the larger



the sample size, the less effect it will have.

Statistical significance

Many biology students seem to have a horror of maths, in which they include statistics.However, there are two principal reasons why this attitude is misplaced:

1. firstly, without statistical analysis, no scientist has any idea of the significance oftheir experimental results. In that regard, statistics is as important a tool in biologyas the microscope;

2. secondly, biologists are not required to understand the mathematics that underpinany of the statistical techniques which they use, although it is essential to be awareof the type of technique that is appropriate to the data to be analysed. Other thanthat, it is just a case of plugging numbers into a formula.

Statistical analysis allows scientists to determine the likelihood of a particular outcome.Results are usually expressed in terms of percentage significance, either 5%(’significant’) or 1% (’highly significant’). These numbers mean that there is only 1chance in 20 (5% level) or 1 chance in 100 (1% level) that such a result would haveoccurred by chance. It is only possible to analyse experimental results statistically ifsamples are randomly selected.

Thus, at the end of vaccine clinical trial, if the number of people in the vaccine groupwho had contracted the disease was lower than the number catching the disease inthe placebo group, the results would be analysed to discover the possibility of such adifference arising by purely random processes. The statistical test would assess howlikely it would be to get such a large difference if the individual subject’s results had justbeen randomly placed into two groups irrespective of their treatment.

The significance of any difference is very strongly dependent on the size of the samplegroups. Quite a large difference may not be found to be statistically significant if thesample size is small, whereas quite small differences may prove significant if the samplesize is large.

Vaccine clinical trials: Questions

Go onlineQ3: Explain what is meant by the statement that vaccine clinical trials should berandomised, double-blind and placebo controlled.

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Q4: State two ways in which increasing sample size will affect the results of anexperiment.

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4.2 Herd Immunity�

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Learning objective


• state that herd immunity is important in the control of infectious diseases;

• state that herd immunity occurs when a large percentage of a population areimmunised;

• explain that, as a result of herd immunity, non-immune individuals are protectedas there is a lower probability they will come into contact with infectedindividuals;

• explain that the herd immunity threshold depends on the disease, the efficacyof the vaccine and the contact parameters for the population.

The creation of herd immunity

When a person is immunised against a disease, it provides protection in two ways.Firstly, should that person meet the pathogen a second time, they are very unlikelyto develop the disease. Secondly, because the pathogen cannot use them as a hostfrom which to spread to other people, the chance of an infection spreading through thepopulation is reduced. This is the basis of the herd immunity which is crucial in thecontrol of infectious diseases.

For an infection to spread through a community, the pathogen must be able to find anew host before its current host’s immune system eliminates it. The fewer contacts theinfected person has with unprotected individuals, the less likely this is. When a certaincritical level of immunisation in the community is reached, the disease will always failto spread in that community, although sporadic cases may occur. In this situation, notonly are those who have been vaccinated protected, but also others who have not, e.g.people whose immune systems have been suppressed for transplant surgery. This isbecause they are less likely to come into contact with infected individuals as there arefew of them and the disease will only be present in the population for a short time.



The three stages of creating herd immunity

Go online

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Most vaccination programmes and policies are aimed at the creation of herd immunity.The childhood vaccination programme in this country ensures that when any of thediseases involved enter the population, they will not spread to create an epidemic andinfect children or adults who have not been previously vaccinated or exposed to thedisease. The creation of herd immunity is especially important in areas where peopleare in close and frequent contact, with the potential for the rapid spread of infection, e.g.schools, densely populated housing.

The creation of herd immunity does not always guarantee success in containing thespread of infectious diseases. Mutations can occur in the pathogen which changes theantigen, an entirely new strain may be brought into the country, or batches of vaccinemay prove faulty. Additionally, if a sufficiently large percentage of the population failsto get vaccinated, the pathogen will be able to find new hosts sufficiently frequently forthe infection to spread and the non-immunised members of the population become veryvulnerable to this disease.

Herd immunity thresholds

The threshold level of vaccination necessary to create herd immunity in a populationvaries from as low as 40% (for Pandemic Flu - H1N1) to up to 94% (pertussis andmeasles). This is dependent on several factors concerned with the pathogen:

• the virulence of the pathogen involved, i.e. how easily it infects people: highervirulence requires a higher threshold;

• the length of time that a person with the disease remains infectious (the period ofinfectivity): the longer the infective period, the higher the threshold;

• the ease of transmission of the pathogen, i.e. how easily the pathogen in passedfrom individual to individual: the more easily the pathogen is transmitted, thehigher the threshold;

• the means of transmission of the pathogen: the more effective the means oftransmission, the higher the threshold.

In addition, some vaccines have a higher efficacy than others, meaning that theyestablish immunity more efficiently and so require a lower level of immunity in thepopulation to contain any disease outbreak. In order to sustain herd immunity, thepopulation may need to receive regular boosters as some vaccinations lose their efficacyover a period of time.

The other factors of importance in determining the threshold level are the contactparameters of the population. This is the extent to which people come into contactwith each other or share the same space; the threshold for an isolated rural communitywill be lower than that for an over-crowded inner city.



The herd immunity thresholds for some diseases are shown in the following table.

DiseaseLikely transmission

methodsHerd immunity threshold

Diphtheria Saliva 84 %

Measles Airborne 86 - 94 %

Mumps Airborne droplet 78 - 86 %

Pertussis Airborne droplet 92 - 94 %

Polio Faecal-oral route 82 - 86 %

Rubella Airborne droplet 82 - 85 %

Smallpox Social contact 80 - 85 %

Pandemic flu Social contact about 40 %

Herd immunity thresholds for vaccine-preventable diseases

In addition to being used in disease prevention, the establishment of herd immunity isalso used to fight ongoing outbreaks of a disease.

Herd Immunity: Questions

Go online

Q5: Explain why herd immunity will protect individuals who are not immune to adisease when an infected person arrives in their community.

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Q6: Explain how each of the following aspects of a pathogen affects the herd immunitythreshold:

• low virulence;

• short infectious period;

• easily transmitted.

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4.3 Immunisation programmes�

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Learning objective


• explain the reasons for public health immunisation programmes;

• state that public health immunisation programmes seek to establish herdimmunity to a number of diseases;

• explain the difficulties caused when widespread vaccination is not possiblebecause of malnutrition, poverty or a vaccine being rejected by a percentageof the population.

The purposes of public health immunisation programmes are to protect vulnerableindividuals, either directly by vaccination or indirectly by establishing herd immunity. Thewinter flu vaccination programmes are an example of protecting vulnerable individualsrather than attempting to reach a threshold of immunity. On the other hand, thechildhood vaccination programmes are very strongly geared to that aim.

Childhood vaccinations in Scotland

Many people will be aware that the routine immunisation of children and infants hasdramatically reduced the incidence of infectious diseases, for example measles andwhooping cough (pertussis), and has led to the global eradication of smallpox. However,for those not recently involved in the rearing of young children, it might come as asurprise just how many vaccinations are routinely given to our children.

While some are tempted to say that the diseases involved are rare and it seems unfair toput young children through the trauma of repeated injections, it only takes a moment’sreflection to appreciate that the risks of any vaccination are minimal compared to thepotential impact of the disease itself, and that the only reason the diseases are rare isthe fact that the vast majority of children are immunised against them.

(Note: the following list is not in the syllabus!)



Childhood vaccinations

Challenges to widespread vaccination

As there are always groups within a community who cannot be vaccinated for variousreasons, e.g. pregnant women, transplant patients, people whose immune systems aredeficient, it is vital that all those for whom the vaccination poses no significant threatare immunised so that the herd immunity threshold is reached. There are three keychallenges to achieving these threshold values:

• malnutrition weakens the immune system so that even if children have beenvaccinated, they will be less able to fight off infection;

• children living in poverty show much lower vaccination rates than more affluentchildren as a result of lower engagement with the public health system;

• vaccination as a process may be rejected by groups on religious or other grounds.

Whereas the first two points can only be addressed by means of improving livingstandards, and are closely inter-related, the latter must be addressed by means ofsensitive education and publicity.



Immunisation programmes: Questions

Go online

Q7: Apart from protecting vulnerable individuals, what do public health immunisationprogrammes attempt to establish?

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Q8: Explain how each of the following reduces the effectiveness of vaccinationprogrammes:

• malnutrition;

• poverty;

• rejection of vaccination.

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4.4 The evasion of specific immune responses bypathogens

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Learning objective


• state that many pathogens have evolved mechanisms that evade the specificimmune system which has consequences for vaccination strategies;

• state that antigenic variation is a process by which a pathogen is able to changeits surface proteins;

• state that antigenic variation may be brought about by:

◦ small genetic mutations that gradually change the surface antigens;

◦ sudden large genetic change when two different strains undergo geneticrecombination;

• explain that antigen variation allows some pathogens to avoid the effect ofimmunological memory;

• describe role and impact of antigenic variation in diseases like malaria,trypanosomiasis and influenza;

• state that some pathogens directly attack the immune system;

• explain that HIV attacks lymphocytes, which is the major cause of AIDS;

• explain that tuberculosis (TB) survives within phagocytes and so avoids immunedetection.

The specific immune system is one of the primary limitations on the replication ofpathogens within the body; these immune responses target specific antigens expressedby the pathogen. However, as a result of a long association with us, many pathogenshave evolved mechanisms that allow them to evade the specific immune system andcause infection. Clearly, such developments must be taken into account when publicvaccination strategies are formulated.

4.4.1 Antigenic variation

Antigenic variation is a process by which a pathogen is able to change its surfaceproteins so that it can evade the host immune responses. The antigenic profile(sometimes called antigenic diversity), will change as the pathogen passes throughthe host population or in the original infected host. Antigenic variation is particularlyimportant for pathogens as it allows them to:

• target hosts which are long-lived or susceptible to the pathogen;

• infect a single host on more than one occasion;

• transmit the disease easily.



Antigenic variation can occur in two distinct ways:

1. the slow accumulation of small genetic mutations (antigenic drift) that graduallychange the surface antigens;

2. a sudden large genetic change (antigenic shift) brought about when two differentstrains undergo genetic recombination.

Antigenic variation

These processes will be explored in more detail when changes in influenza viruses arestudied.



Pathogens which undergo antigenic variation have a selective advantage over moregenetically stable ones. Antigenic variation happens through three genetic processes:

1. gene mutation;

2. recombination;

3. gene switching, which occurs when certain members of a family of genes areswitched on while others in the family shut down - it is a process that is commonduring embryonic development.

The resulting pathogens are immunologically different from the parental strains. Thus,pathogens which can vary their antigenic signature are able to avoid triggering theimmunological memory which had been developed in response to their parental strain.

Antigenic variation: Question

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Q9: List the genetic processes which cause antigenic variation.

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4.4.2 Antigenic variation in different pathogens

Viruses

The influenza virus genome is fragmented and can go through a high rate of geneticre-assortment during replication. This can result in the emergence of a new virusthat codes for a new haemagglutinin (HA) and/or neuraminidase (NA); the two largeglycoproteins on the outside of the viral particles. Most flu epidemics are due to theemergence of these new virus strains (usually type A) and can be brought about viaantigenic shift and antigenic drift.

Drift and shift in flu viruses



Antigenic shift in flu viruses can occur when:

• an aquatic bird passes a bird strain of influenza A to an intermediate host suchas a chicken or pig and a person passes a human strain of influenza A to thesame chicken or pig - when the viruses infect the same cell, the genes from thebird strain mix with genes from the human strain to yield a new strain, which canspread from the intermediate host to humans;

• an avian strain of influenza A (without undergoing genetic change) jumps directlyfrom a duck or other aquatic bird to humans;

• an avian strain of influenza A (without undergoing genetic change) jumps directlyfrom a duck or other aquatic bird to an intermediate animal host and then tohumans.

This genetic change enables influenza strains to jump from one animal species toanother, including humans. What happens, in fact, is that when two strains of thepathogen recombine, any one of the eight influenza proteins can be replaced by adifferent protein acquired as a result of genetic re-assortment. In this case, the RNAthat codes for the HA is replaced for one from another source (i.e. from avian or porcinesources). This is illustrated below; the change of the glycoproteins (HA) on the surfaceof the viral particles is illustrated by a colour change on the surface of the virus.

Diagrams of a highly pathogenic avian strain virus and a human strain

The influenza pandemic of 1918-19 was caused by a virus which had a HA proteinnormally found in swine influenza strains. Antigenic shift results in a more immediateand extensive change in the genetic information of this ’newly formed’ pathogen.

These changes in the haemagglutinin and neuraminidase types are used to characterisethe various strains of the flu viruses. Some of the variants that caused notable epidemicsare shown below.



Flu pandemics since 1890: the ’Spanish’, ’Asian’ and ’Hong Kong’ strains of flu involveavian variants; the ’swine’ strain has porcine variants

In terms of the global impact, the 1918 Spanish Flu pandemic was by far the worst, withan estimated 50 to 100 million deaths worldwide.

Antigenic drift is a result of genetic point mutations accumulated by the viral genomeover an extended period of time. This drift results in small antigenic changes in thepathogen population and will reduce the efficacy of B and T cell memory during the hostimmune response. Antigenic drift is prominent in the influenza virus, and is becomingmore and more evident in the rapid evolution of rhinoviruses and enteroviruses.Antigenic drift contributes to our susceptibility to influenza infections year after year.The human immunodeficiency virus (HIV) exhibits antigenic drift within the particularhost due to its high rate of replication.

Protozoa

Antigenic variation occurs in diseases such as malaria and trypanosomiasis and is oneof the reasons why they are still so common in many parts of the world.

Protozoa represent the most biologically complex pathogens presented to the humanimmune system. Trypanosomes (causing sleeping sickness) and Plasmodium (causingmalaria) use antigenic variation to evade immune responses and prolong the duration ofinfections. Trypanosomes exhibit unique processes of gene conversion, whereby anyone of hundreds of genes coding for variable surface glycoproteins can be expressed.As the Trypanosomes multiply inside the host, the host makes antibodies against them.After five to seven days, these antibodies destroy most of the Trypanosomes and thesymptom decreases. About this time, a new wave of Trypanosomes appears becausethese are unaffected by antibodies generated against the previous wave. The immunesystem has to start over again. This process continues, essentially indefinitely, untilthe death of the host. During this time, the body continues to make primary responsesagainst new antigens. One consequence of this is that the immune system becomesquite exhausted and the blood levels of the antibody (immunoglobulin IgM) increasedramatically, but to no useful effect.



In the protozoa Plasmodium falciparum, an aetiological agent (aetiology is the studyof causes or origins) for malaria undergoes gene switching, resulting in the variableexpression of surface proteins produced on infected red blood cells during theerythrocytic, asexual phase. These protozoan processes of antigenic variation leadto a gradual exhaustion of the host immunity in the terminal stages of disease.

Antigenic variation in different pathogens: Questions

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Q10: Explain what is meant by gene conversion in Trypanosomes.

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Q11: How does gene conversion provide Trypanosomes with the ability to evade thehost immune system.

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4.4.3 Direct attack on the immune system�

�

�

�

Learning objective


• explain why the absence or failure of some components of the immune systemresults in increased susceptibility to infection;

• explain how HIV attacks lymphocytes and is the major cause of acquiredimmunodeficiency in adults;

• explain how the pathogen which causes Tuberculosis (TB) can survive withinphagocytes and avoids immune detection.

Some pathogens directly attack the immune system by destroying lymphocytes. TheHuman Immunodeficiency Virus (HIV) is the best known example.

HIV and AIDS

Acquired Immune Deficiency Syndrome (AIDS) is the fatal condition that results frominfection with HIV. AIDS itself is not a disease but describes the opportunistic diseasesthat infect and are often fatal to an HIV-positive individual. It is widely accepted that HIVdevelops into AIDS, although there have been a few cases where people have remainedcompletely symptomless.

HIV is carried in the blood, semen, vaginal fluids and breast milk, but it is unable tosurvive outside of the human body for long so can only be transmitted by the exchangeof body fluids. The main ways in which HIV can be transmitted between people are:

• intimate sexual contact;

• intravenous drug use and blood transfusions;

• from mother to child across the placenta and through breast milk.

The vast majority of infections occur as a result of sexual intercourse, both heterosexualand homosexual. The virus that causes this disease is a lentivirus (slow virus) that



infects both the immune and central nervous systems over a period of years. Manypeople experience flu-like symptoms when they are first infected and become HIV-positive, but serious symptoms do not generally appear until years later. As the HIVmultiplies, it weakens the immune system by destroying the T-helper cells that mediatethe immune response, as shown below. Eventually the immune system is destroyed,making sufferers more susceptible to diseases. As sufferers are immunocompromised,these diseases are more harmful and are frequently fatal. As the T-helper cellsare destroyed and the immune system is less able to defend the body opportunisticinfections occur, such as:

• oral thrush, caused by the fungus Candida albicans;

• Kaposi’s sarcoma, a rare form of skin cancer;

• tuberculosis;

• a rare form of pneumonia caused by Pneumocystis carinii.

Graphs of HIV concentration and T-cell concentration

Initially, it was thought that HIV and AIDS only affected homosexuals and drug usersbecause most of the first cases were seen in these two groups. It is now known thatanyone can be infected with HIV, but there is still a lot of stigma associated with thedisease.

Direct attack on the immune system: Question

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Q12: Why does HIV cause AIDS?

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4.4.4 Tuberculosis

Tuberculosis (TB) is a contagious disease caused by the bacteria Mycobacteriumtuberculosis (human) and M. bovis (cattle). It is transmitted in the same way as thecommon cold - by droplets from the respiratory tract of individuals that have the activedisease. When they cough, sneeze, talk or spit, tiny droplets containing the bacteriumare expelled from their lungs, which may then be inhaled by other people. Only afew bacilli are required for a person to become infected, making this disease easilytransmissible. It is also possible to become infected with M. bovis via contact withsusceptible animals and their products (e.g. unpasteurised milk); this form of TB ismore common in economically less developed countries.

Not all people infected with TB are actually infectious. Only those who actually developTB symptoms are infectious, but, if untreated, they can potentially infect 10-15 othersevery year. It is estimated that at any one time a third of the world’s population is infectedwith TB, but only a small number will develop the disease. However, tuberculosiscontinues to kill more than two million people every year, a figure that is rising as theAIDS epidemic increases and drug-resistant TB spreads.

TB can be categorised into three types:

1. in the majority of cases, the immune system of the infected person kills the bacteriaand the person experiences no further symptoms;

2. latent TB, in which the sufferer does not experience any symptoms, but thebacteria remain in the body, surviving within phagocytes and thus avoidingdetection - latent TB can sometimes develop into an active TB infection, especiallyif the infected person’s immune system is weakened;

3. active TB, in which the immune system fails to kill or contain the infection and itslowly spreads to the person’s lungs.

The bacteria that cause tuberculosis can remain inactive in a human for many years,but can become active if its host’s immune system has been weakened. This causesserious complications for people who are already immunocompromised, such as thoseinfected with HIV. It accounts for the majority of AIDS deaths.

Tuberculosis spreads rapidly in overcrowded areas and outbreaks are often seen amongthe poor and homeless. The incidence of TB in economically more developed countrieswas considerably reduced when the standards of housing and nutrition improved. Theintroduction of a vaccine further decreased the impact of TB and it was thought that ithad almost been eradicated from the developed world. However, it is now making acomeback as inner city poverty, homelessness, drug resistance, AIDS and migration tobig cities are all rising. Drug resistance in Mycobacterium is also developing by naturalselection, particularly as a result of people failing to complete courses of antibiotics.

Tuberculosis: Question

Go onlineQ13: How does TB evade detection by the immune system?

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4.5 Learning points

Summary

Active Immunity

• Active immunity can be developed by vaccination with antigens frominfectious pathogens.

• Vaccination creates an immunological memory.

• Vaccines include antigens from infectious pathogens, including inactivatedpathogen toxins, dead pathogens, parts of pathogens and weakenedpathogens.

• The antigens in vaccines are usually mixed with an adjuvant to enhance theimmune response.

Vaccine Clinical Trials

• Key aspects of the protocol for any vaccine clinical trial are that the trialshould be:

◦ randomised;◦ double-blind;◦ placebo-controlled.

• The importance of group size in reducing experimental error and increasingstatistical significance.

Herd Immunity

• Herd immunity is important in the control of infectious diseases.

• Herd immunity occurs when a large percentage of a population areimmunised.

• As a result of herd immunity, non-immune individuals are protected as thereis a lower probability they will come into contact with infected individuals.

• The herd immunity threshold depends on the disease, the efficacy of thevaccine and the contact parameters for the population.

Immunisation programmes

• The reasons for public health immunisation programmes.

• Public health immunisation programmes seek to establish herd immunity toa number of diseases.

• Difficulties arise when widespread vaccination is not possible because ofmalnutrition, poverty or a vaccine being rejected by a percentage of thepopulation.

The evasion of specific immune responses by pathogens



Summary continued

• Many pathogens have evolved mechanisms that evade the specific immunesystem which has consequences for vaccination strategies.

• Antigenic variation is a process by which a pathogen is able to change itssurface proteins.

• Antigenic variation may be brought about by:

◦ small genetic mutations that gradually change the surface antigens;

◦ sudden large genetic change when two different strains undergogenetic recombination.

• Antigen variation allows some pathogens to avoid the effect ofimmunological memory.

• The role and impact of antigenic variation in diseases such as malaria,trypanosomiasis and influenza is to continuously alter the surface antigensof the pathogens, leading to sporadic epidemics and the failure ofvaccination programmes.

• Some pathogens directly attack the immune system.

• HIV attacks lymphocytes, which is the major cause of AIDS.

• Tuberculosis (TB) survives within phagocytes and so avoids immunedetection.



You should have a good understanding of public health immunisation programmesbefore attempting the question.


Extended response question: Public health immunisation programmes

State the aim of public health immunisation programmes and explain why they may failto protect non-immunised individuals. (6 marks)

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End of Topic 4 test

Go online

Q14: Complete the paragraphs by selecting words from the list. (12 marks)

An immunological �� can be developed by �� with antigens frominfectious ��. This is known as �� immunity. Vaccines include�� from infectious pathogens, including inactivated pathogen ��,dead pathogens, parts of pathogens and weakened pathogens. The antigens invaccines are usually mixed with an �� to enhance the �� response.

Key aspects of the �� for any vaccine clinical trial are that the trial should be��, double-blind and placebo-controlled. Group size is important in reducingexperimental �� and increasing �� significance.

Word list : active, adjuvant, antigens, error, immune, memory, pathogens, protocol,randomised, statistical, toxins, vaccination.

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Q15: Explain the term ’antigenic variation’. (1 mark)

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Q16: Describe one way in which pathogens develop antigenic variation. (2 marks)

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Q17: State the role of antigenic variation in diseases like malaria, trypanosomiasis andinfluenza. (1 mark)

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Q18: State the impact of antigenic variation in such diseases. (1 mark)

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Q19: Explain how HIV leads to the development of AIDS. (2 marks)

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Q20: State how TB evades immune detection. (1 mark)

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81

Topic 5

End of unit test

82 TOPIC 5. END OF UNIT TEST

End of Unit 4 test

Go onlineQ1: An example of the body’s physical barriers to infection is: (1 mark)

a) epidermisb) histaminesc) sebum

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Q2: Histamines are released by: (1 mark)

a) mast cellsb) NK cellsc) phagocytes

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Q3: Cytokines stimulate the: (1 mark)

a) apoptosisb) non-specific immune responsec) specific immune response

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Q4: Autoimmune diseases are caused by an incorrect response by: (1 mark)

a) B-lymphocytesb) macrophagesc) T-lymphocytes

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Q5: Community responsibility for control of pathogen spread involves: (1 mark)

a) good hygieneb) sexual healthc) waste disposal

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Q6: A disease which is always present in a population is: (1 mark)

a) endemicb) epidemicc) pandemic

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Q7: Vaccines contain pathogen: (1 mark)

a) antibodiesb) antigensc) antiseptics

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TOPIC 5. END OF UNIT TEST 83

Q8: Herd immunity thresholds are less likely to be reached because of: (1 mark)

a) malnutritionb) poor personal hygienec) unsafe food webs

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Q9: Name an example of the body’s non-specific chemical defences againstpathogens and state its function. (2 marks)

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The graph shows the immune response of two people, one of whom has beenvaccinated against a disease and the other not.

Q10: Which of the two lines on the graph represents the response of a person who hasbeen vaccinated against the disease? (1 mark)

a) Ab) B

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Q11: Explain the response of a person who has been vaccinated against the disease.(1 mark)

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Q12: In the later stages of the infection, a person infected with HIV would show adifferent pattern to either of these curves. Describe this difference. (1 mark)

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Q13: Explain this difference. (1 mark)

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84 TOPIC 5. END OF UNIT TEST

The following diagram shows clonal selection in lymphocytes.

Q14: Describe what is shown in the upper half of the diagram. (1 mark)

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Q15: Explain the lower half of the diagram. (2 marks)

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Q16: State how some T-lymphocytes activate B-lymphocytes. (1 mark)

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Q17: State two ways in which pathogens may be transmitted. (1 mark)

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Q18: How does quarantine control the spread of a pathogen? (1 mark)

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Q19: State the three key aspects of the protocol for any vaccine clinical trial. (1 mark)

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Q20: Describe the importance of group size in vaccine clinical trials. (2 marks)

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Q21: Explain how antigenic variation enables a pathogen to evade the specific immuneresponse. (2 marks)

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GLOSSARY 85

Glossary

Acquired immunity

immunity developed throughout a person’s life time; can be induced either naturallyor artificially

Arthropods

invertebarate animals with a segemented body, jointed limbs and an externalexoskeleton, e.g. insects, crustaceans and arachnids

Enterovirus

a virus which causes diseases such as polio and meningitis

Erythrocytic asexual phase

the pathogenic portion of the vertebrate phase of the life cycle of malarialorganisms that takes place in the red blood cells

Gene conversion

occurs during DNA genetic recombination and at high frequencies during meiosis;it is one of the ways a gene may undergo mutation

HA

(haemagglutinin) a protein that mediates the binding of the virus to target cells

Influenza A

a virus which causes influenza in birds and mammals; Influenza B and C aremainly confined to humans

Innate immunity

inborn immunity

Lysis

cell breakdown

Lysozyme

an enzyme found in tears, saliva, and mucus which can destroy bacteria

NA

(neuraminidase) involved in the release of progeny virus from infected cells

Phagocytes

white blood cells that protect the body by ingesting/phagocytosing harmful foreignparticles, bacteria, and dead or dying cells

Phagocytosis

the engulfing of pathogens or solid material into a vesicle with which lysosomesthen fuse, releasing their digestive enzymes into it

Rhinovirus

one of the viruses which cause the common cold


86 GLOSSARY

Trypanosomiasis

diseases caused by the protozoa Trypanosomes such as sleeping sickness andChagas disease


ANSWERS: TOPIC 1 87

Answers to questions and activities

1 Non-specific defences

The immune system: Questions (page 3)

Q1: To protect the body against pathogens, some toxins and cancer cells.

Q2: Skin epithelial cells and lysozyme in tears and saliva.

Q3: It degrades bacterial walls.

Q4: This is immunity that is inborn, non-specific, and does not change over time.Any two examples from:

• phagocytosis by phagocytes;

• skin epithelial cells;

• mucus membranes of the lungs and gut;

• ciliated cells of the respiratory tract;

• lysozyme in tears.

Q5: A type of white blood cell which engulfs bacteria.

Non-specific defences - physical and chemical: Questions (page 5)

Q6: Any two from:

• dry dead cells;

• tiny hairs;

• mucus in the trachea.

Q7: Sebum contains antimicrobial fatty acids and the stomach produces acidsecretions.

The cellular basis of inflammation: Questions (page 9)

Q8: In connective tissue, especially around nerves and blood vessels.

Q9: It stimulates vasodilation and increases permeability of capillary walls.

Q10: Cytokines

Q11: Phagocytes / macrophages / neutrophils

Q12: Phagocytosis

Q13: Complement system

Q14: Fibrinogen and fibrin


88 ANSWERS: TOPIC 1

Phagocytes: Questions (page 12)

Q15: Cytokines

Q16: To stimulate the specific immune response.

Q17: Antigen molecules on the cell surface.

Q18: Engulfing and digesting solid particles.

Natural killer (NK) cells: Questions (page 14)

Q19: Self-destructive enzymes

Q20: Apoptosis

Extended response question: The inflammatory response (page 15)

Suggested marking scheme

Each line represents a point worth one mark. The concept may be expressed in otherwords. Words which are bracketed are not essential. Alternative answers are separatedby a solidus (/); if both such answers are given, only a single mark is allocated. Inchecking the answer, the number of the point being allocated a mark should be writtenon the answer paper. A maximum of eight marks can be gained.

1. Mast cells. . .

2. . . .release histamine.

3. Histamine causes vasodilation. . .

4. . . .and increases capillary permeability.

5. Mast cells also secrete cytokines.

6. Cytokines act as signalling molecules.

7. The increased blood flow and the secretion of cytokines lead to. . .

8. . . .the delivery of antimicrobial proteins. . .

9. . . .and clotting elements to the site of infection/damage.


ANSWERS: TOPIC 1 89

End of Topic 1 test (page 15)

Q21:

The immune system protects the bodyagainst

pathogens.

Sebum on the skin contains fatty acidswith

antimicrobial properties.

Pathogens find the dry outer layers ofthe skin to be

a hostile environment.

Mast cells release histamine.

Histamine causes vasodilation.

Cytokines act as signalling molecules.

Increased blood flow leads to delivery of clotting elements.

Phagocytes are attracted by cytokines.

Q22:

The white blood cells involved in the non-specific response are phagocytes andnatural killer (NK) cells. Both phagocytes and NK cells release cytokines whichstimulate the specific immune response.

Phagocytes target pathogens which they recognise by the antigen molecules on theircell surface. They then destroy them by engulfing and digesting them in a processcalled phagocytosis.

The NK cells release enzymes which induce infected cells and pathogens to producethe self-destructive enzymes of apoptosis pathways.

Q23: To protect the body against pathogens.

Q24:

• It has antimicrobial chemicals/sebum on its surface.

• Its dry outer layers are a hostile environment for pathogens.

Q25: Mast cells

Q26: Causes vasodilation AND increases capillary permeability.

Q27: Cytokines

Q28: They attract phagocytes (to the site of infection).

Q29:

• Antimicrobial proteins.

• Clotting elements.


90 ANSWERS: TOPIC 1

Q30:

• Phagocytes.

• Natural killer/NK cells.

Q31: Antigens on the cell surface.

Q32: Engulfing (and digesting) of solid particles.

Q33: Self-destructive enzymes

Q34: Apoptosis


ANSWERS: TOPIC 2 91

2 Specific cellular defences

Immune surveillance: Questions (page 20)

Q1: Mast cells

Q2: Neutrophils

Q3: Cytokines

Q4: Lymph nodes

Q5: They present fragments of the cell membrane of engulfed pathogens, which carrythe antigens which uniquely identify the pathogen, on their cell surface.

Clonal selection theory: Questions (page 22)

Q6:

1. In the red bone marrow, haematopoietic stem cells divide to produce daughter cells.

2. As a result of genetic rearrangement, during differentiation these immaturelymphocytes each develop a different antigen receptor on their cell membranes.

3. Those immature lymphocytes, which carry a receptor that will bind with an antigenfrom the body’s own tissues, are destroyed in the bone marrow.

4. The lymphocytes that carry other antigen receptors are released from the bonemarrow and move through the circulatory system to the lymph glands or thymusgland where they mature into inactive lymphocytes.

5. Most of these inactive lymphocytes will never encounter an antigen to match theirreceptor.

6. Inactive lymphocytes, which do meet an antigen matching their receptor, becomeactivated and divide to produce many clones of themselves.

Q7: The way in which lymphocytes are developed to respond to specific antigens.

Q8: 1

T- and B-lymphocytes: Questions (page 25)

Q9: Antigens on foreign cells, cells infected by pathogens and toxins released bypathogens.

Q10: They have specific surface proteins.

Q11: A failure of immune system regulation, leading to a response by T-lymphocytes toself antigens.

Q12: They secrete antibodies into the blood and lymph.

Q13: A hypersensitive B-lymphocyte response to an antigen that is normally harmless.


92 ANSWERS: TOPIC 2

The action of T-lymphocytes: Questions (page 27)

Q14: Apoptosis

Q15: By engulfing pathogens.

Q16: Cytokines

Q17: Antigens expressed on the surface of antigen-presenting cells.

The action of B-lymphocytes: Questions (page 29)

Q18: Antigen-presenting cells/macrophages, T-lymphocytes

Q19: A group of cells which are produced by mitosis from a single parent cell.

Q20: Antibodies

Q21: The antibody will only attach to one particular antigen.

Q22: An antigen-antibody complex

Q23: They block their binding sites.

Q24: They cause them to cluster together/agglutinate.

Q25: Antibodies attach to the surface of the pathogens.The antigen-antibody complex stimulates the complement system.Complement proteins form pores in the pathogen membrane, causing lysis.

Immunological memory: Questions (page 31)

Q26: Activated lymphocytes in the lymph nodes

Q27: They are rapidly stimulated to divide and produce a new clone of lymphocytes.

Q28: It is faster and involves greater production of antibodies.


ANSWERS: TOPIC 2 93

Extended response question: Clonal selection theory (page 33)


Each line represents a point worth one mark. The concept may be expressed in otherwords. Words which are bracketed are not essential. Alternative answers are separatedby a solidus (/); if both such answers are given, only a single mark is allocated. Inchecking the answer, the number of the point being allocated a mark should be writtenon the answer paper. A maximum of six marks can be gained.

1. Clonal selection theory explains the way in which lymphocytes are developed torespond to specific antigens which invade the body.

2. Antigens are molecules on the surface of pathogens and other foreign cells ormaterials which activate the immune system.

3. Lymphocytes have a single type of receptor on the cell membrane.

4. This receptor is specific to one antigen.

5. Antigen binding leads to repeated lymphocyte division. . .

6. . . .which results in a clonal population of lymphocytes.


Q29:

Constantly monitoring the tissues: white blood cells.

Identify pathogens to the immune system: antigens.

Released by damaged cells: cytokines.

Attracted to infected tissues: monocytes.

Located on the cell membrane of lymphocytes: receptors.

Receptor only binds to one antigen: specific.

A response by T-lymphocytes to the body’s own antigens: autoimmune.

A hypersensitive response by B-lymphocytes: allergic.


94 ANSWERS: TOPIC 2

Q30:

T-lymphocytes destroy infected cells by inducing apoptosis.

T-lymphocytes secrete cytokines that activate B-lymphocytes.

Antigen-presenting cells activate the production of a clone of T-lymphocytes.

B-lymphocytes are activated by antigen-presenting T-lymphocytes.

Each B-lymphocyte clone produces a specific antibodymolecule.

Antigen-antibody complexes render pathogenssusceptible to

phagocytosis.

Cell lysis is a response stimulated byan antigen-antibodycomplex.

Q31: They have specific surface proteins that allow them to distinguish between thesurface molecules of the body’s own cells and cells with foreign molecules on theirsurface.

Q32: They divide repeatedly to produce clones of B-lymphocytes that secreteantibodies into the lymph and blood.

Q33: A second exposure to the same antigen stimulates memory cells to divide rapidlyand produce new clones of lymphocytes which produce a secondary response that ismuch more effective in terms of antibody production.


ANSWERS: TOPIC 3 95

3 The transmission and control of infectious diseases

Infectious diseases caused by pathogens: Question (page 41)

Q1:

Type of pathogen Example of disease

Bacteria Pneumonia

Fungi Candidiasis

Prion CJD

Protozoa Malaria

Virus Herpes

Methods of transmission of pathogens: Question (page 43)

Q2:

Method of transmission Example of disease

Body fluids HIV

Direct physical contact MRSA

Food Typhoid

Indirect physical contact Gastroenteritis

Inhaled air Measles

Vectors Dengue fever

Water Dysentery

Control of spread of pathogens: Questions (page 48)

Q3: Keeps individuals who have potentially been infected separate from healthyindividuals.

Q4: The use of chemicals which either kill or inhibit the growth and reproduction ofpathogens.

Q5:

• Care in the storage and handling of food.

• Care in sexual health.

• Good personal and domestic hygiene.


96 ANSWERS: TOPIC 3

Q6:

• Appropriate waste disposal system.• Safe supply chains of foods.• Supply of water of a quality that is safe to drink.

Q7: The spread of diseases which are contracted from vectors can be reduced byremoval of vector habitat, the sterile male technique, or the use of pesticides.

Epidemiology and the spread of disease: Question (page 50)

Q8:

The disease occurs occasionally in a population: sporadic.

Cases of the disease occur regularly in an area: endemic.

There are unusually high numbers of cases in an area: epidemic.

Unusually high numbers of cases in many countries: pandemic.

Control measures: Questions (page 52)

Q9: c) Isolation

Q10: c) Immunisation

Q11: b) Antibodies

Extended response question: Control of spread of pathogens (page 53)



1. Quality of water supply - drinking water must be safe to drink.

2. Not contaminated with sewage.

3. Free from harmful chemicals and bacteria.

4. Supervision of food chains - enforcing minimum hygiene standards.

5. In abattoirs, restaurants, fast-food outlets, supermarkets, market stalls. (any two)

6. Health education.


ANSWERS: TOPIC 3 97

7. Waste disposal - refuse collection.

8. Sewage treatment.


Q12:

Pathogens may be transmitted by direct physical contact, water, food, body fluids,inhaled air or vector organisms. The spread of pathogens can be controlled byquarantine and antisepsis.

Individuals have a responsibility to control disease by means of good hygiene, carein sexual health and appropriate storage/handling of food. The role of community isto ensure the quality of water supply, safe food webs, and appropriate waste disposalsystems. Communities may also reduce the spread of disease by means of programmesof vector control.

Q13: Quarantine keeps people who have been potentially exposed to an infection. . .. . .separate from the rest of the population.

Q14:

• Purify water before supplying it to households.

• Ensure sewage and drinking water are kept separate.

Q15: Disease: malaria / dengue. (or other suitable)Spread control: removal of areas of stagnant water / other breeding areas, e.g. oldtyres.

Q16: A disease that is found at a constant low level in a population.

Q17: By the introduction of a new strain of the disease against which there is noimmunity.


98 ANSWERS: TOPIC 4

4 Active immunisation

Active immunity: Questions (page 59)

Q1:

Component Function

Antigen Creates immunological memory

Adjuvant Enhances immune response

Q2:

• Dead pathogens.

• Inactivated pathogen toxins.

• Parts of pathogens.

• Weakened pathogens.

(two sources for one mark, all four for two marks)

Vaccine clinical trials: Questions (page 62)

Q3: Randomised - all subjects in the trial should have an equal chance of being givenvaccine or the placebo.Double-blind - neither the subjects nor the persons carrying out the trial know whichsubjects are getting the vaccine and which the placebo.Placebo-controlled - the trial subjects are divided into two groups, one receiving thevaccine and the other a treatment which is similar in all respects to the vaccine apartfrom the active ingredient being tested (the placebo).

Q4: Increasing sample size reduces the effect of experimental error. . .. . .and increases the statistical significance of the results

Herd Immunity: Questions (page 66)

Q5: Herd immunity reduces the chances of non-immune individuals coming in contactwith an infected person.

Q6:

• Low virulence - decreases the threshold.

• Short infectious period - decreases the threshold.

• Easily transmitted - increases the threshold.


ANSWERS: TOPIC 4 99

Immunisation programmes: Questions (page 69)

Q7: Herd immunity

Q8:

• Malnutrition: weakens the immune system so that even if children have beenvaccinated, they will be less able to fight off infection.

• Poverty: children living in poverty show much lower vaccination rates than moreaffluent children, as a result of lower engagement with the public health system.

• Rejection of vaccination: vaccination as a process may be rejected by certaingroups on religious or other grounds, reducing the percentage of the populationwhich is immunised.

Antigenic variation: Question (page 72)

Q9:

1. gene mutation;

2. recombination;

3. gene switching.

Antigenic variation in different pathogens: Questions (page 75)

Q10: It occurs when one of hundreds of genes coding for variable surface glycoproteinsare expressed.

Q11: A new wave of Trypanosomes appears which are unaffected by the currentantibodies.

Direct attack on the immune system: Question (page 76)

Q12: The HIV virus destroys (T-helper) lymphocytes, which weakens the immunessystem and allows other infections to produce the symptoms of AIDS.

Tuberculosis: Question (page 77)

Q13: It survives within phagocytes.


100 ANSWERS: TOPIC 4

Extended response question: Public health immunisation programmes (page 79)



1. Public health immunisation programmes seek to establish herd immunity to anumber of diseases.

2. Herd immunity occurs when a large percentage of a population are immunised.

3. This percentage is called the herd immunity threshold.

4. Non-immune individuals are protected because there is a lower probability theywill come into contact with infected individuals.

5. Difficulties arise when widespread vaccination is not effective because ofmalnutrition, which weakens the immune system. . .

6. . . .or poverty, which reduces vaccination rates. . .

7. . . .or a vaccine being rejected by a percentage of the population.


ANSWERS: TOPIC 4 101


Q14:

An immunological memory can be developed by vaccination with antigens frominfectious pathogens. This is known as active immunity. Vaccines include antigensfrom infectious pathogens, including inactivated pathogen toxins, dead pathogens,parts of pathogens and weakened pathogens. The antigens in vaccines are usuallymixed with an adjuvant to enhance the immune response.

Key aspects of the protocol for any vaccine clinical trial are that the trial should berandomised, double-blind and placebo-controlled. Group size is important in reducingexperimental error and increasing statistical significance.

Q15: A process by which a pathogen is able to change its surface proteins so that it canavoid the effect of immunological memory.

Q16: Either one of:

• The slow accumulation of small genetic mutations (antigenic drift). . .. . .that gradually change the surface antigens.

• A sudden large genetic change (antigenic shift). . .. . .brought about when two different strains undergo genetic recombination.

Q17: To continuously alter the surface antigens of the pathogens.

Q18: Causes sporadic epidemics and the failure of vaccination programmes.

Q19: HIV attacks lymphocytes which reduces the effectiveness of the immunesystem. . .. . .allowing other pathogens to invade and kill the host.

Q20: It survives within phagocytes.


102 ANSWERS: TOPIC 5

5 End of unit test

End of Unit 4 test (page 82)

Q1: a) epidermis

Q2: a) mast cells

Q3: c) specific immune response

Q4: c) T-lymphocytes

Q5: c) waste disposal

Q6: a) endemic

Q7: b) antigens

Q8: a) malnutrition

Q9: Name: sebum (or other suitable)Function: contains antimicrobial chemicals.

Q10: a) A

Q11: It is quicker and greater because memory cells have been activated.

Q12: The curve would be slower to rise and would peak much lower.

Q13: HIV destroys the B-lymphocytes which release the antibodies.

Q14: Lymphocytes have a single type of receptor on the cell membrane which is specificto one antigen.

Q15: Antigen binding to receptors on lymphocyte ’Y’ leads to repeated lymphocytedivision. . .. . .which results in a clonal population of type ’Y’ lymphocytes only.

Q16: They secrete cytokines.

Q17: Any two from:

• body fluids;

• food;

• inhaled air;

• physical contact;

• vector organisms;

• water.

Q18: Individuals who are infected or have been in contact with an infected person areisolated.


ANSWERS: TOPIC 5 103

Q19: They must be:

1. double-blind;

2. placebo-controlled;

3. randomised.

Q20: Increasing group size reduces experimental error. . .. . .and increases statistical significance.

Q21: It enables a pathogen to change its surface proteins.Memory cells are no longer activated by the new antigens.


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