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Biomedicine

THE IMMUNE SYSTEM

Copyright CNM – College of Naturopathic Medicine 1

THE IMMUNE SYSTEM The Immune System is a set of protective measures used by the body to defend itself from all kinds of invaders

3 ‘Routes’ of Entry for Pathogens: 1.Respiratory Tract

2.Digestive tract

3.Break in Skin

3 ‘Lines’ Protection providing 2 Main Types of Defence:

1st Line = EXTERNAL = Barriers, Secretions & Excretions

2nd Line = INTERNAL = Antimicrobial Cells, Proteins & Processes (Inflammation & Fever)

3rd Line = INTERNAL & Specialized

Cell & Antibody Mediated

Non-Specific /

Innate Defence

Specific Defence/

Adaptive Immunity

1

2

2

ANTIGENS Def: Any substance that when introduced to the

body, has the POTENTIAL to trigger an Immune Response, especially the production of Antibodies.

Two types:

1. FOREIGN SUBSTANCES (Microbes, Food, Dust, Drugs

etc.)

2. SELF ANTIGEN (present on cell membranes)

http://www.beltina.org/health-dictionary/antigen-antibody-what-are-definition-cancer.html

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Non-specific Defence Mechanisms

1st Line of Defence

1. Skin & Mucous Membranes =

BARRIERS:

• Physical Barrier – Closely packed Keratinized cells

• Periodic Shedding of skin cells helps remove microbes

• Mucus produced by Mucous Membranes traps microbes and foreign particles

• Mucocilliary Escalator move mucus and trapped microbes & foreign microbes to the throat where it can be swallowed

• Hair Filter in the nose

4

2. ‘FLUIDS/ EXCRETIONS/ SECRETIONS’- Flushing out microbes

• TEARS – Dilute microbes and stops them settling on eye surface

• SALIVA – Cleanses the oral cavity • PERSPIRATION – Helps to flush microbes from skin surface • VAGINAL SECRETIONS – Acidic & Move microbes out of female body • One way flow of URINE & FAECES

• VOMITING and DIARRHOEA – Usually a response to Microbial Toxins


1st Line of Defence

5

Contain

Lysozymes &

Secretory IgA

3. ANTI-MICROBIAL SUBSTANCES

• GASTRIC ACID – Destroys pathogens in swallowed mucus and ingested substances

• SEBUM – Contains Fatty Acids which inhibit microbe growth

• TEARS, SALIVA & PERSPIRATION - Contain Lysozyme, an enzyme that breaks down bacteria

• VAGINAL SECRETIONS – Slightly acidic to discourage bacterial growth


1st Line of Defence

6

These include:

• Internal anti-microbial proteins

• Phagocytes

• Natural killer cells

• Inflammation

• Fever

7

Non-specific Defence Mechanisms INTERNAL Defences:

2nd Line of Defence

Anti-microbial Proteins -

INTERFERONS (IFN’s)

• A cytokine protein

produced by a cell

infected with a virus.

• Helps to stop

replication of

viruses within other

cells

• 3 main types: alpha,

beta and gamma

8

Digression: Cytokines

• Umbrella term for MANY types of small PROTEINS secreted

by Leukocytes.

e.g. Interferon & Interleukin = Cytokine made by leukocytes and act on other leukocytes) (Intermediary)

• Assoc. with Immunity, Inflammation, Fever &

Haematopoiesis

• Short-acting

May act on :

a. The cells that secreted them,

b. Nearby cells

c. Distant cells (rarest)

Immune- modulating, Cellular- Communicators.

e.g. Interferons and Interleukins

9


COMPLEMENT SYSTEM • A system made of over 30 proteins

produced by the Liver and found circulating around the body.

• Complement proteins are identified by a letter with a number e.g. C3

• Normally inactive but when activated these proteins act in a cascade to ‘complement’ Immune Processes.

• Collectively, complement proteins destroy microbes & promote Immunity by...

– Promoting Phagocytosis

– Contributing to Inflammation

– Causing Cytolysis (bursting) of Microbes

10

Complement Cascade may be activated in 3 ways

i. Classical Pathway – Activation of

Complement System when antigen-antibody complexes formed

ii. Alternative Pathway – Direct activation of

complement by Lipid-carbohydrate Markers

already on invading cells’ surface (Pathogen

Surface Markers)

iii. Lectin Pathway – Macrophages digest

microbes, releasing chemicals that cause the

LECTIN production by the liver, which help to

activate complement

1. Opsonization – Invaders tagged for

Phagocytosis

2. Attract Macrophages

3. Stimulate Mast cells to release

Histamine – Promote inflammation

4. Initiate Cytolysis - Produce Membrane

Attack Complex

1

2 3 4

i ii

11

Complement - Cytolysis • The final five proteins in the complement cascade attach

to the plasma membrane of the invading microbe

• They form a membrane-attack complex (MAC) which inserts into the plasma membrane forming a channel

• Extracellular fluid flows into the invading microbe through the new channel, causing it to swell and burst.

12 http://www2.estrellamountain.edu/faculty/farabee/biobk/biobookimmun.html


TRANSFERRINS • Iron-binding proteins

that inhibit the growth

of certain bacteria by

inhibiting the

available iron that

they need for growth

• Creates an

environment low in

iron by binding iron -

Bacteria cannot

survive 13

Phagocytosis

• Cell eating

• Phagocytic cells are attracted to sites of inflammation by chemotaxis

• Non selective in their targets: Engulf and digest anything foreign

• Antigen presentation to T-lymphocytes by macrophages

A scanning electron

microscope image of a single

neutrophil (yellow), engulfing

anthrax bacteria (orange).

14

Phagocytosis Phagocytosis occurs in 5 stages:

1. Chemotaxis – Release of chemicals by microbes, WBCs, damaged

tissue & by activated complement that attract macrophages

2. Adherence – Binding of phagocyte to target. (Aided by complement)

3. Ingestion – Microbe/foreign matter is engulfed

4. Digestion – Lysosomes fuse with ingested matter and release lysozymes .The microbe/foreign matter is broken down and

destroyed by the enzymes and chemicals produced in the phagocyte

5. Excretion/ Presentation- Release or Presentation of digested material

15

PHAGOCYTES

• Specialised cells that Engulf and digest anything foreign (cellular and foreign material).

• The two major types are Macrophages (Monocytes in Blood) and Neutrophils, which migrate to an infected area

• Some other kinds of phagocytes are Fixed such as:

Histiocytes (Connective tissue),

Kupffer cells (Liver)

Alveolar Macrophages (Lungs),

Microglia (Nervous tissue)

Tissue Macrophages (Spleen, Bone marrow & Lymph Nodes)

Langerhans Cells (Skin) Antigen-presenting Cells -process & present antigens to T-cells.

16

NATURAL KILLER CELLS • Non-specific lymphocyte

• Attack anything that they do not recognise, including

abnormal body cells

• Present in blood, lymph nodes, spleen and bone marrow

• Binding to a target cell causes release of granules

containing the protein perforin

• Perforin inserts into the plasma membrane and creates a

channel for tissue fluid to flow into the cell – Cytolysis

• This causes apoptosis

17

Summary Type of

defence

Interferons Complement Transferrins NK cells Phagocytes

Cell or

Protein?

How does

it work?

What does

it attack?

18

INFLAMMATION

Non- specific immune defence to tissue damage

Causes of inflammation:

• Pathogens

• Abrasions

• Chemicals

• Cells distortion or disturbance

• Extreme temperatures

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The Inflammatory Response

Clinical signs of inflammation:

- Redness (rubor)

- Heat (calor)

- Pain (dolor)

- Swelling (tumor)

- Loss of function

20

Inflammatory Response Stages 3 STAGES:

1. Vasodilation and Increased permeability of blood vessels

2. Emigration of Phagocytes from the blood and interstitial fluid

3. Tissue Repair

1. VASODILATION & INCREASED PERMEABILITY

• Vasodilation allows extra blood to the area, bringing oxygen, nutrients, immune cells and repair substances as well as aiding removal of toxins and dead cells

• Increased permeability permits immune cells and defensive proteins such as antibodies and clotting factors into the tissue.

• Together these create the Redness, Swelling & Heat

• Pain results from injury to neurons and toxic chemicals released by microbes

• Pain is prolonged and intensified by Kinins and Prostaglandins released during the inflammatory process

http://www.goodpsych.com/storage/inflammation.jpg

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2. EMIGRATION OF PHAGOCYTES

• Within an hour of initial inflammation

• numbers of WBC migrate to site due to Chemotaxis

• Neutrophils are first on the scene, followed by monocytes (in blood) and

macrophages (in tissues). • Dead phagocytes accumulate as pus PUS = Dead Phagocytes (N), cell debris, fibrin,

inflammatory exudate and living and dead microbes

3.TISSUE REPAIR 22

Substances which contribute to inflammation

1. Histamine - Released in response to injury by mast cells and basophils

2. Leukotrienes - Released by basophils and mast cells. Attract phagocytes and aid adherence of phagocytes to pathogens

3. Kinins – Induce vasodilation and increased permeability. Attract phagocytes. Example: Bradykinin

4. Prostaglandins - Released by damaged cells. Enhance effects of histamine and kinins as well as stimulating emigration of phagocytes

5. Complement system – See before

INFLAMMATORY

MEDIATORS

23

Benefits of Inflammation 1. Promotion of Phagocytosis – Phagocytic cells are attracted by

Chemotaxis and the Temperature (caused by inflammation)

promotes their activity

2. Promotion of Immune Response – Protective proteins such as

Antibodies can leave blood stream and enter the tissues as blood

vessels become more permeable

3. Toxin Dilution – Accumulation of Fluid dilutes damaging toxins

and waste materials

4. Fibrin Formation – Damaged cells promote the formation of a

fibrin network. This can...

• WALL OFF the inflamed area preventing

spread of infection

• Help BIND wound edges during healing

Some bacteria such as Streptococcus pyrogenes (tonsillitis, pharyngitis,

some skin infections) can break down fibrin so that the infection can

spread.

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Harmful Effects

of inflammation

1. SWELLING- In a confined space, can cause severe Pain due to

Pressure on nerves. Can Also be DANGEROUS (ICP)

2. PAIN - Occurs when swelling compresses the Sensory Nerve

endings and as a Reaction to Chemical Mediators

like Bradykinin, Prostaglandins etc.

3. SUPPURATION / PUS FORMATION

PUS = Dead Phagocytes, Dead cells, Debris, Fibrin, Inflammatory Exudate & living/dead Microbes.

Main Cause = Staphylococcus aureus &

Streptococcus pyrogenes

4. ABSCESS FORMATION = Localized, Painful

accumulation of Pus, surrounded by Inflamed Tissue

5. ATHEROSCLEROSIS

6. ADHESIONS & SCAR TISSUE

Larynx

25

ABSCESSES SUPERFICIAL ABSCESSES tend to Rupture

through the skin and Discharge pus

DEEP SEATED ABSCESSES can...

1. Rupture through the skin

2. Rupture with minimal discharge - developing a Chronic

Abscess with an infected open channel or Sinus

3. Rupture & Discharge pus into an adjacent organ forming a

Fistula = an infected channel open at both ends.

4. Become enclosed by Fibrous Tissue becoming a source of further

infection

5. Form Adhesions

6. Cause Shrinkage of fibrous tissues

7. Heal

A pilonidal sinus

is a small hole or

tunnel in the skin,

usually at the very

top of the cleft

between the

buttocks 26

OUTCOMES of Inflammation

1. RESOLUTION – Cause is successfully overcome

2. May become CHRONIC INFLAMMATION - Similar to acute inflammation but more body TISSUE is likely to be DESTROYED.

3. GRANULOMA -If the body defences cannot clear the infection, they can wall it off ie. form Granuloma

Tuberculosis is an example of

an infection which

frequently becomes

chronic.

The mycobacterium is

resistant to phagocytosis 27

4. FIBROSIS- Scar Tissue Formation Occurs in healing when:

- There is loss of tissue

- Cells don‘t regenerate

- Can be a result of chronic inflammation

Scar tissue consists of collagen fibres

secreted by Fibroblasts

It can have Damaging Effects like...

1. Adhesions

2. Fibrosis of Thrombus or embolus blocking a blood vessel

3. Tissue shrinkage Tissue shrinkage after

a burn

OUTCOMES of Inflammation

Adhesions can cause problems such as Infertility & Intestinal obstruction

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FEVER

• Abnormally high body temperature

• Occurs because the hypothalamus thermostat is reset

• Common in infection/inflammation

• Can be triggered by bacterial toxins which cause macrophages to release fever causing chemical called cytokines. One example is interleukin-1

• High body temperature: – Makes interferons more effective

– Inhibits growth of some microbes

– Speeds up the reactions that aid repair 29

Worksheet

• Please fill in the

Inflammation

Summary

worksheet

30

Cells of the Immune System

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Cells of the Immune System

• Basophils and Mast cells - Chemotaxic

• Eosinophils – Protect against large microbes

such as parasites and worms

• Neutrophils - Protect against foreign

invaders

• Monocytes and Macrophages - Produce

interleukin which promotes fever, globulin

production and T-cell activation.

• Lymphocytes - T and B cells and NK Cells.

Part of specific immunity

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Granulocytes

• Single multi-lobular nucleus

• Granules in the cytoplasm

They are:

• Basophils

• Eosinophils

• Neutrophils

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Basophils & Mast Cells

• Contain Heparin (anticoagulant) + Histamine (vasodilator) and other things that promote inflammation (Leukotrienes & Cytokines).

• Not phagocytic

• In Blood = Basophil

• In Tissue = Mast cells

• Anaphylaxis- Basophils have IgE protein receptors on their cell surface that bind IgE antibody very tightly.

Increasing Inflammation!

•Yobos of the immune system = Inflame the situation!

34

Eosinophils / Acidophils

• Eliminate parasites

• Promote

inflammation

• Migrate due to

allergic reaction

• Phagocytosis and

chemotaxis

Eosinophils Eliminate Extra-large Enemies

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Neutrophils

“Swallowing up your enemies!” -Phagocytosis

• Migrate towards infection site WITHIN an HOUR!

• Phagocytosis- using lysosomes which they can not renew

• They DIE after having phagocytised a few pathogens

• Their activity and death in large numbers forms PUS.

Fair fighters of the immune system

Numerous Neutrophils Neutralise 36

Neutrophils

Raised in:

• Strenuous exercise

• Microbial infection

• Tissue damage

• Metabolic disorders

• Leukaemia

• Heavy smoking

• OCP use

Numerous Neutrophils Neutralise

37

Agranulocytes:

Monocytes & Macrophages

• In Blood: Monocytes

• In Tissue: Macrophages

• Form: – Kupffer cells

– Microglia

– Langerhans Cells

– Peyer's Patches etc.

• Both Monocytes/Macrophages secrete Cytokines e.g. Interleukin 1

1. Induce Fever

2. Produce Globulins

3. Activate T-cell

38

RECALL: Cytokines

• General name for MANY types of small PROTEINS

secreted by Leukocytes.

• e.g. Interleukin = Cytokine made by leukocytes and act on other leukocytes) (Intermediary)

• Assoc. with Immunity, Inflammation, Fever &

Haematopoiesis

• Short-acting

• May act on :

a. The cells that secreted them,

b. Nearby cells

c. Distant cells (rarest)

Immune- modulating, Cellular- Communicators.

e.g. Interferons and Interleukins

39

Monocytes & Macrophages

Monocytes • Large, phagocytic

• Mono-nuclear, no lobes

• Some become macrophages

• Increased with microbial infection

Macrophages • Protection! (Defence) via Phagocytosis &

• Isolating dangers (Walling off)

• Release cytokines (inflammatory signals)

• Immune system- Stimulate lymphocytes &

other immune cells to respond to the pathogen.

(Innate Immunity)

• Inflammation

• Repair & Clean up Police Patrols – Protect, Prevent,

“Pick up the Pieces” 40

Lymphocytes

Lymphocytes Developed in the

bone marrow

T-lymphocytes

Cytotoxic Memory

Helper Regulatory/

Suppressor

B-lymphocytes

Memory Plasma Cells

41

B & T Cells

• IMMUNOCOMPETENT

– They learn to respond to Antigens

(foreign material)

– They learn to respond to Immune Labels

1. Possess specificity for antigens: Recognise self

from non-self molecules (Each B cell and T cell is

specific for a particular antigen. So each is able to

bind to a particular molecular structure.

2. Possess memory for previously encountered

Antigens: They can mount a greater attack next time.

T-Lymphocyte

42

B & T Cells

• T cells are made in the Bone marrow

and mature in the Thymus

• Most T cells arise before puberty but continue to

mature and leave the Thymus throughout life

• The 2 Major types of T Cells:

T-helper 1 (Th1) - Involved in Cell Mediated Immunity

T-helper 2 (Th2) - Involved in Antibody Mediated Immunity

The balance between the 2 is maintained

by Another type of T Cell = Regulatory T Cells / Suppressor T

Cell.

• B cells are made in the Bone marrow and mature

continually (mostly in Bone Marrow).

B-Lymphocyte

43

B and T cells

T-lymphocytes

• Made in Bone marrow.

• Processed ( & mature) in the Thymus (Lymphoid

Organ)

• Numerous in Lymph nodes

• Attack Antigens: Cell Mediated Immunity

• Antibody mediated too

B-lymphocytes

• Made in Bone marrow.

• Processed in the Bone marrow

• Mature in Lymph organs (Bone marrow, Lymph nodes & Lymph Glands)

• Numerous in Lymph nodes

• Produce Antibodies (Immunoglobulins): Antibody mediated immunity

44

SELF TOLERANCE

& SELF RECOGNITION

• To function properly, T cells must be able to recognise the body’s own Immune Labels (Self-Recognition) and own Proteins (Self-Tolerance)

• They learn how to do this in the Thymus

• T-cells that don’t display proper self recognition (immune labels) and self tolerance (proteins) are deleted or inactivated

• Only about 1-5% of T-cells make it through the screening process!

• B cell also have to be self tolerant so they undergo a similar screening process in the Bone marrow

45

White Blood Cell Summary Cell Neutrophil Eosinophil Basophil Monocyte T-Lymphocyte B-Lymphocyte

Phagocytic

Involved in allergy

Converted to

macrophages

Release histamine

Numerous in the

lymph nodes

Kupffer cells

Increased numbers

in infection

Kill parasites

Known as mast

cells when present

in the tissues

Mature in the

thymus 46

Specific Defence =

Adaptive Immunity Mediated (brought about) by B & T-lymphocytes

1. CELL-MEDIATED IMMUNITY: (T- Lymphocytes)

Immunity provided via (production of) Cytotoxic T cells/

Killer T cells

Defence against Intra-cellular Pathogens, Cancer Cells and

Transplants

2. ANTIBODY-MEDIATED/ HUMORAL IMMUNITY:

(mainly B- Lymphocytes)

Immunity provided via Antibodies (Immunoglobulins)

Defence against extracellular Pathogens 47

Cell Mediated Immunity AKA Antigen Presentation

T-lymphocytes have been activated in the Thymus

and are released into the circulation.

• For the T-lymphocytes ‘to get sensitised’ to their antigen, the antigen must be presented to the cell, usually by a Macrophage

• Cancer cells can also present

their antigen to T-lymphocytes.

See next slide for

details of this process

48

1. A T-cell (TH-1) doesn’t recognise an antigen in

the body (Because antigen doesn’t fit into T-Cell receptor) until it is

presented to it. Active T-cells have to be ‘sensitized’

to the antigen.

2. & 3. So, Antigen- presenting / Dendritic /

Phagocytic cells engulf the antigen and then use

enzymes to break the antigen into fragments

(process the antigen). Some antigen fragments are combined with

Human Leukocyte Antigen Molecules (HLA)

4. These fragments are then displayed on the

phagocytic cells’ surface and presented to a T-

lymphocyte which can now recognise the

antigen

5. The T-lymphocyte binds onto the antigen and

releases IL-2.

6. This then initiates the T-lymphocyte to

proliferate and differentiate into Cytotoxic/killer,

Memory and Helper T-cells (Clonal Selection)

49

Diversion: Interleukin-2

• = Cytokine

• Produced by a leukocyte, acting on a

leukocyte

• Causes growth, proliferation & activation

of NK cells, T and B cells

• Produced by T-helper cells when they bind

to an antigen

50

CLONAL SELECTION

• Def: Cloning of selected Lymphocytes in the lymphatic organs and tissue, under influence of IL-2

• In Cell Mediated Immunity, IL-2 is

released by the T-cells when an

Antigen binds to the T-cell receptor.

• This then stimulates the activated T-

cell to Proliferate & Differentiate.

• This is why you get swollen lymph

nodes or tonsils when you’re ill !

• Three main types of T-cells are produced (see next slide)

• ALSO SEEN IN ANTIBODY-

MEDIATED IMMUNITY!!

51

1. Cytotoxic T-lymphocytes : Bind and destroy the antigen

2. Memory T-lymphocytes: Recognize antigen for next

time, ready to mount a second immune reaction

3. Helper T-lymphocytes: Release cytokines which

potentise T, B and NK cells. (Positive feedback)

52

T-cells produced

during Clonal Selection

http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m4/s9/trm4s9_1.htm

53

Specialized, subpopulation of T cells which send messages to and so "de-activate" the other immune cells (T-Helper, B Cells & Macrophages) when an immune response is no longer required.

Thereby maintain immune system homeostasis and tolerance to self-antigens.

Without the Regulatory T cells, the body would continue trying to fight off a disease that no longer exists (and eventually would end up fighting its own cells).

This is an important regulatory, "self-check“ mechanism built into the immune system to prevent excessive reactions

Regulatory T Cells (Tregs ) (Formerly Suppressor T Cells)

Worksheet

• Please fill in your Cell Mediated Immunity

worksheet

54

Mediated by B cells • B-lymphocytes are fixed in

lymphoid tissue (Spleen and Lymph Nodes).

• They can recognise and bind antigens without prior presentation.

• Once the B-lymphocyte has bonded to an antigen, a Helper T-lymphocyte stimulates it (Activates it by releasing IL-2) to enlarge then Divide, Proliferate & Differentiate

• CLONAL SELECTION!!

http://dev.nsta.org/evwebs/1887/immune%20system.JPG 55

Antibody-Mediated Immunity (Humoral Immunity)

Two types of cells are

produced:

• Plasma cells

– Secrete antibodies

into the blood.

– Only produce one

type of anti-body

– Short lived

• Memory B-cells – Long lived

– Remember/

Recognize antigen for

next time, ready to

proliferate and

produce more plasma

cells for a second

immune reaction

Antibody-Mediated / Humoral

Immunity

Antibody-Antigen Complex

http://dev.nsta.org/evwebs/1887/immune%20system.JPG 56

T-Helper Lymphocyte

Activated B-Lymphocyte

57

Clonal Selection in

Antibody-Mediated / Humoral Immunity

http://nfs.unipv.it/nfs/minf/dispense/immunology/lectures/files/adaptive_immunity.html

INTERDEPENDENCE

of B & T cells

58

Worksheet

• Please fill in your Antibody Mediated/

Humoral Immunity Worksheet

59

ANTIBODIES

Belong to a group of

proteins called Globulins –

Immunoglobulins

Bind to antigens forming

Antibody-Antigen Immune

Complexes

Highly Specific – Antibody

fits to antigen like a lock and

key

60

1. Neutralising – Neutralise Bacterial TOXINS or prevent viral attachment to cells

2. Immobilising – Bind to antigens on bacterial cilia or flagella

3. Agglutinating & Precipitating – Cause antigen carrying matter to clump together /become insoluble making it easier to for phagocytic cells to engulf

ANTIBODY CLASSES

61

Binding of Antibodies to Antigens inactivates Antigens by:

1 3 3

http://www.austincc.edu/apreview/EmphasisItems/Inflammatoryresponse.html

ANTIBODY CLASSES

4. Activating complement – Antigen-antibody complexes activate the Classical Complement pathway

5. Enhancing Phagocytosis – Acts as a flag to attract phagocytes Also aid phagocytosis via agglutination, precipitation and complement activation.

62

4

5

http://www.austincc.edu/apreview/EmphasisItems/Inflammatoryresponse.html

Antibody

TYPE

Where is it

found?

How common

is it?

What does it do?

IgG

Blood, lymph &

intestines

Most common –

makes up 80% of

all antibodies in

the blood

Protects against bacteria and viruses by

neutralising toxins, enhancing phagocytosis and

activating complement

It is the only antibody that can CROSS the

PLACENTA

IgA

Sweat, Tears,

Saliva, Breast-

milk, GI-

Secretions

Smaller amounts

in blood and lymph

10-15% of

antibodies in the

blood

Localised PROTECTION of MUCOUS

MEMBRANES against bacteria and viruses

Levels are decreased during stress!

IgM

Blood and lymph

B cell surface

5-10% of

antibodies in the

blood

Activates complement. Causes agglutination and lysis

of microbes

Antigen receptors on B cells

Anti-A and anti-B antibodies of the ABO- BLOOD

GROUPING system

IgD

B cell surface 0.2% of antibodies

in the blood

B cell antigen receptors – Involved in B cell

activation

IgE

Located on Mast

cells and

Basophils

Less than 0.1% of

antibodies in the

blood

Involved in ALLERGIC reactions:

Provide PROTECTION against PARASITIC worms

Serum IgE levels rise in parasitic diseases, measuring

IgE levels is helpful in diagnosing parasitic infections.

63

IMMUNOLOGICAL MEMORY

Basis of Vaccination

• Based on the presence of long lasting antibodies and

very long lasting Memory B & Memory T cells

• PRIMARY (1ST) RESPONSE (1st Exposure/

Sensitisation in Allergy)

– Slow response as not many cells have the correct

specificity to respond to the antigen (not been

activated) so response can take several days

64

IMMUNOLOGICAL MEMORY

Basis of Vaccination

• SECONDARY RESPONSE (Subsequent Exposure/

Exaggerated Immune Response- Allergy!!)

Much faster response because a full immune response has

been developed with thousands of memory cells present to

proliferate and differentiate into active B and T cells

There are also more antibodies readily available which have

a greater affinity for the antigen.

Often the secondary response is so effective it kills off the

microbe before you exhibit any signs or symptoms

PLEASE SEE SLIDES ON ALLERGIES 65

• Immunological Memory is the basis for vaccination against certain

diseases

1. Vaccines contain Attenuated (weakened) /Killed, Whole/Portions

of Microbes

This ensures the Microbes are Immunogenic but NOT Pathogenic

i.e. They cause an immune response but not the illness

2. This activates the B and T cells = Primary Response. Not many

cells have the correct specificity to respond to the antigen, so a

response can take several days.

3. Subsequent exposure to the Living Pathogen initiates a far more

Effective Secondary Response- This response is much quicker as

thousands of Memory cells are now present to Proliferate and

Differentiate into Active B & T cells, often without any symptoms

being experienced.

66

IMMUNISATION / VACCINATION

VACCINATION

• Diseases preventable

by vaccination....

– Anthrax

– Cholera

– Diphtheria

– Hepatitis B

– Measles

– Mumps

– Poliomyelitis

– Rubella

– Smallpox

– Tetanus

– Tuberculosis

– Typhoid

– Whooping cough

67

Acquired Immunity

• It is possible to acquire immunity both actively

and passively, by either natural or artificial

means.

Active

Immunity

Natural

Artificial

Passive

Immunity

Natural

Artificial

68

Acquired Immunity

• Naturally acquired active immunity • Natural exposure to a disease either clinical presentation or sub-

clinically

• Naturally acquired passive immunity • Transfer of IgG antibodies across the placenta from mother to

child.

• Transfer of IgA antibodies from mother to child via the breast milk

• Artificially acquired active immunity • Vaccination

• Artificially acquired passive immunity • Injection with immunoglobulin (antibodies) e.g. Snake anti-venom

69

Worksheet

• Please fill in the acquired immunity worksheet

70

Types of Immune Reaction I) Anaphylaxis, Food Allergy, Hay fever, Eczema, Irritant Contact

Dermatitis (ICD)

II) Autoimmunity- Rheumatoid Arthritis, Haemolytic Dx of Newborn

& Blood Transfusion Reactions

Exposure to allergen/ antigen activates IgEs, l.t. degranulation of Mast cells and Basophils = Release of histamine, Leukotrienes etc. which l.t. bronchoconstriction, vasodilation (BP) & oedema of tissue within 5-10 min of exposure to allergen/ antigen. (ONSET IS IMMEDIATE)

Antibodies (IgG & IgM) produced by the immune response bind to antigens on the cell or

tissue surface (attacks cells & tissues).Activates complement system and lymphokines.

ONSET IS IMMEDIATE 71

Types of Immune Reaction III) Glomerulonephritis , Penicillin Allergy & SLE

Antibody-Antigen Complexes form aggregates which are not cleared and so deposited in various tissues (esp. skin, kidney, joints), triggering an immune response I.e. activate complement system. IgG, IgM, IgA, mediated. ONSET IN 4-8 HOURS

Cell Mediated, NOT antibody-mediated. Over-reaction of T-lymphocytes to an antigen

= Massive Clonal expansion = large numbers of Cytotoxic T cells and inflammatory chemicals, which can damage normal tissues.

DELAYED ONSET / REACTION = 48-72 hours 72

IV) Skin Graft Rejection & Allergen Contact Dermatitis (ACD)

PROBIOTICS, DIGESTIONS

& IMMUNITY

ACQUIRED IMMUNITY

Gut Associated Lymphoid Tissue

• About 70% of the body's Immune System is found in the Digestive Tract.

• The GALT includes several types of Lymphoid Tissues that store Immune

cells, such as T and B lymphocytes.

• Example of GALT:

Tonsils, Adenoids (Pharyngeal Tonsils), Peyer's Patches & Appendix

Probiotics Pathogens

INNATE IMMUNITY of the GIT Wall (BASIC DEFENCE)

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IMMUNE SYSTEM

PATHOLOGIES

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ALLERGY

Examples of Allergens:

• Certain Foods

• Animal Dander

• Mites

• Dust

• Chemicals/ detergents/ perfumes/soaps/

• Latex

• Pollen

Def: Powerful Immune Response to an Allergen Allergen = Antigen that generates allergy.

The allergen itself is usually harmless, it is the immune response that causes damage to the body

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ALLERGY • Initial Exposure = Sensitisation (Slow

response as not many cells have the correct specificity to respond to the antigen /allergen (not been activated). So this response can take several days

• Subsequent Exposure = Exaggerated Immune Response

• The full immune response has been developed and antibodies are readily available!

• Symptoms can range from mild presentation such as running nose and streaming eyes to anaphylaxis which can be fatal

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Food Allergy vs. Intolerance

• True food allergy only affect 2% of adults and 6% of

children

• It is an IgE -Mediated Immune Response that can be

triggered by even the smallest amount of food

• Far more people have a Food Intolerance –

unpleasant symptoms triggered by eating a

significant quantity of a particular food and lacking

Probiotics, Enzymes, Bile, HCL or other Digestive

Factors needed to deal with the food.

• Food intolerance does not have a defined immune

response

• Example of a food intolerance: Lactose intolerance

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Anaphylactic Shock

• Severe, Systemic, Allergic Response within 5-10 mins of exposure to an antigen.

• Inherited high levels of IgE

• Exposure to allergen causes IgEs to activate mast cells and basophils – Release of histamine

• Causes bronchoconstriction, vasodilation, oedema of tissue

• Rx: Epi-pen

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AUTO IMMUNE CONDITIONS

Autoimmunity = The immune system failing to display Self Tolerance and Self Recognition

Auto antibodies = Antibodies/ Immunoglobulins & Cytotoxic T-Cells formed against self Antigens.

• The Antibody-Antigen reaction leads to Complement Activation, Inflammation and Tissue damage

• Autoimmunity often has a Genetic link – Tend to run in families.

• Some disorders affect specific tissue others are generalised

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Systemic Lupus Erythematosus

A chronic autoimmune, Connective Tissue disease that can affect ANY part of the body

Cause:

1. AUTOIMMUNE

• B-cell activation increased IgG levels against DNA, platelets,

erythrocytes, nucleic acid and other nuclear materials

• Inability to remove immune complexes from tissue - Complement is

activated causing inflammation

• Impaired T-cell regulation

• Abnormal cytokine production

2. Can be caused by DRUGS: Flare-ups can be induced by OCP & HRT

3. GENETIC

4. ENVIRONMENTAL ( UV light, mercury, pesticides exacerbate it)

80


Varies in manifestation:

• Fever

• Depression

• Photosensitivity

• Butterfly Rash

• Vasculitis, purpura,

urticaria

• Pleurisy

• Raynaud’s

• Polyarthralgia

• NS damage

• Heart damage

• Abdominal pain

• Renal disease

• Anaemia

Signs & Symptoms: The course of the disease is unpredictable, with periods of illness

(called flares) alternating with remissions.

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Investigations-

• Full blood count,

• Antinuclear antibody test

• Rheumatoid factor

• Complement levels

• Anti-phospholipids antibodies: IgG, IgE

• ESR

Management

• Immunosuppressive

• NSAIDS 82

Rheumatoid Arthritis

Chronic, Systemic Inflammation of many tissues, primarily the Synovium (potentially all organs except brain)

• Affects 1% people worldwide

• C: Considered to be Autoimmune

• Rheumatoid Factor (RF) - an Auto-antibody which can bind to other antibodies- is directed against a portion of IgG

• The resultant Immune Complex activates Complement proteins leading to inflammation and damage.

• RF is Present in the majority of suffers (~80%)but not all. RF may also be present in other conditions

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Sgs & Sxs:

• Symmetrical arthritis of hands/feet

• Distal joints affected first

• Gradually spreads proximally

• Swelling/stiffness worse in morning

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• Other Sgs & Sxs : – Eye problems – Pain in eyes or

dry eyes

– Subcutaneous nodules

– Neurological complications, especially due to erosion of the C2 odontoid peg, or cruciate ligament supporting this part of the neck

– General malaise

– Atlatoaxial subluxation and compression of the spinal cord quadriparesis.

– Kidney problems 85


Complications:

• Muscle atrophy

• Mal-alignment of the joints

• Deformity of the joints

Management:

• Physiotherapy

• Pain control: NSAIDs Steroids

• Surgery

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Ankylosing Spondylitis (AS)

• Chronic inflammation of spine and sacroilliac joints, often leading to spinal fusion (ankylosis) and reduced movement

Ankylosing = immobility of a joint

Spondylitis = inflammation of a vertebra

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Cause:

• Autoimmune with a genetic basis

• 95% of patients test positive for the HLA–B27 Gene

• Age of onset 20–45.

• 1/3 have a family history

• M:W – 8:1

• No direct diagnostic tool

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Sgs & Sxs :

• A sufferer presents with low back pain, possibly radiating into posterior thighs.

• Stiffness and pain is marked in the mornings,

and improves with activity.

• Sometimes systemic signs like fatigue, fever,

weight loss, eye inflammation

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Ankylosing Spondylitis

• Early Sgs: Lumber lordosis

flattens, mobility reduced

• Later Sgs: Thoracic kyphosis

restricted, rib joints stiffen, chest

expansion diminished

• Hip and heel pain are common.

• 20% suffer acute iritis.

• Mild: 90% of suffers, settles in

the 4th decade.

• Severe spinal restriction: 10%,

often with hip disease. 90

Management: • Physiotherapy

• Anti-inflammatory drugs 91

Hashimoto’s Thyroiditis

• Organ specific, Autoimmune

condition affecting the Thyroid

gland

• The thyroid gland is gradually

destroyed by a variety of Cell and

Antibody -mediated immune

processes.

• Auto-antibodies develop that

react with Thyroglobulin and

Thyroid Cells. This prevents the

synthesis of thyroid hormones

causing hypothyroidism with

occasional bouts of

hyperthyroidism.

• More common in women than men

Antibody-mediated

Cell -mediated

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Grave’s Disease

(Thyrotoxicosis)

Autoimmune (IgG) antibodies bind to TSH receptor and stimulate production of thyroid hormones

Rx:

Radioactive iodine,

Surgery

Anti-thyroid (Thyrostatic) drugs such as Carbimazole

& beta blockers such as Propanolol

Bulging eyes (Exophthalmos /

Proptosis ).

Graves' Ophthalmopathy

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Role of Lymphatic and Immune

Systems in Homeostasis Whole body:

• Immune cells and antibodies protect the body from foreign invaders, foreign cells and cancer cells

• Lymphatic system drains excess tissue fluid

Integumentary system:

• Langerhans cells help protect the skin

• Lymphatic tissue provides IgAs in sweat

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Skeletal and muscular systems:

• Lymphatic vessels drain excess tissue fluid and leaked plasma proteins from the muscle tissue and connective tissue surrounding bones

Endocrine system:

• Lymph flow helps distribute some hormones and cytokines


Systems in Homeostasis

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Cardiovascular system:

• Lymph returns excess fluid and leaked plasma proteins to the blood stream

• Macrophages in the spleen destroy old red blood cells

Respiratory system:

• Tonsils, alveolar macrophages and MALT help protect the lungs from pathogens

Urinary system:

• MALT defends against pathogens that penetrate the body via the urethra



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Digestive system:

• Tonsils and MALT defend against pathogens entering the GI tract

• IgA antibodies in saliva

• Lymphatic vessel pick up absorbed dietary lipids and fat soluble vitamins from the small intestine and transport them to the blood



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Reproductive system:

• MALT helps defend against pathogens entering via the vagina/penis

• IgG antibodies can cross the placenta to provide protection for the developing fetus

• IgA antibodies are passed to the neonate via the breast milk



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Quiz!

• Teams of 4

• Decide on a team name

• 33 Questions

• Possible 77 marks

• Write neatly so the

marking team can read

you answers!

99

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