CHAPTER 43

THE BODY’S DEFENSES

The Nature of Disease

• Pathogenic OrganismsPathogenic Organisms• Genetic DisordersGenetic Disorders• Toxic ChemicalsToxic Chemicals• Other Environmental FactorsOther Environmental Factors• Physical Damage to OrgansPhysical Damage to Organs• Nutritional DisordersNutritional Disorders

Types of Pathogenic Organisms

• VirusesViruses• BacteriaBacteria• ProtozoanProtozoan• FungiFungi• AnimalAnimal• ParasitesParasites

Mechanisms of Disease by Pathogens

• Utilization of host nutritional Utilization of host nutritional resourcesresources

• Physical damage to host tissuesPhysical damage to host tissues• Production of toxic substancesProduction of toxic substances• Chromosomal and gene damageChromosomal and gene damage• Body cells behave abnormallyBody cells behave abnormally

Viruses

nucleic acid

capsid

envelope

Bacteria

cell wall

plasma membrane

cytoplasm

circular DNA

Defense Mechanisms1. External defense2. Internal Defense3. Immune Defense

• Skin acts as barrier to microbes and viruses- sweat has a low pH

• Mucus traps foreign particles• Tears

- Lysozyme has antimicrobial action• Gastric stomach acid

1st Line of Defense

Body Coverings: The Skin

sebaceous glands

sweat gland

epidermis

Body Coverings: Mucous Membranes

mucus

cilia

columnar epithelium

• Phagocytic cells (WBCs)- N L M E B- Natural Killer (NK) Cells: attack virus

infected cells• Inflammatory Response• Antimicrobial proteins

- Lysozyme- Interferon- Antibodies

2nd Line of Defense

Nonspecific Phagocytosis

NeutrophilsMonocytesEosinophils

Mechanism of PhagocytosisMechanism of PhagocytosisMechanism of Phagocytosis

MacrophageMacrophage

Lymphatic System

Inflammatory Response

Histamine & prostaglandins released

Capillaries dilateClotting begins

Chemotactic factors attract phagocytic cells

Phagocytes consume pathogens & cell debris

Characteristics of Immunity

• Recognition of self versus non-self• Response is specific• Retains a “memory” allowing an

accelerated second response• Can respond to many different

materials• Involves lymphocytes and

antibodies

Types of Immunity

• Active Immunity- Naturally-Acquired Active Immunity- Artificially-Acquired Active Immunity

• Passive Immunity- Naturally-Acquired Passive Immunity- Artificially-Acquired Passive Immunity

Types of Acquired Immunity

• The production of antibodies against a specific disease by the immune system.

• Naturally acquired through disease • Artificially acquired through vaccination

– Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but weakened microbes.

• Active immunity is usually permanent

Active Immunity

• A vaccinated person has a secondary response based on memory cells when encountering the specific pathogen.– Routine immunization against infectious

diseases such as measles and whooping cough, and has led to the eradication of smallpox, a viral disease.

– Unfortunately, not all infectious agents are easily managed by vaccination.• HIV vaccine in the works

• Passive Immunity- Protection against disease through antibodies produced by another human being or animal.

• Effective, but temporary• Ex. Maternal antibodies• Colostrum.

Passive Immunity

• Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal.– Rabies treatment: injection with antibodies

against rabies virus that are both passive immunizations (the immediate fight) and active immunizations (longer term defense).

Immune System Response to Antigens

Humoral Immunity• Involves antibodies (secreted from B

cells) dissolved in the blood plasma.• Demonstrated as a immune response

using only the blood serum.• Defense against bacteria, bacterial

toxins, & viruses.

Cell-Mediated Immunity• Involves the activities of specific

white blood cells (T cells).• Defense against cancer cells, virus-

infected cells, fungi, animal parasites, & foreign cells from transplants.

Immune System Response to Antigens

Lymphocyte Formation

B Cells• Mature in bone marrow• Involved in humoral immunity• Once activated by antigen,

proliferate into two clones of cells: plasma cells that secrete antibodies and memory cells that may be converted into plasma cells at a later time

B Cellsantibodies

B CellsB Cells

Activation of B Cells by Antigen

antigen

Clonal Selection

Clonal Selection

plasma cells memory cellsantibodies

Humoral Immune Response

time (days)

antib

ody

conc

entra

tion

first exposure to antigen A

Humoral Immune Response

time (days)

antib

ody

conc

entra

tion

first exposure to antigen A

primary response: concentration of anti-A antibodysecond exposure

to antigen A

Humoral Immune Response

time (days)

antib

ody

conc

entra

tion

secondary response: concentration of anti-A antibody

second exposure to antigen A

first exposure to antigen B

Humoral Immune Response

time (days)

antib

ody

conc

entra

tion

primary response: concentration of anti-B antibody

first exposure to antigen B

• Antibodies constitute a group of globular serum proteins called immunoglobins (Igs).– A typical antibody molecule has two identical

antigen-binding sites specific for the epitope that provokes its production.

Antibody Moleculeantigen binding sites

antigen

light chains heavy chains

Mechanisms on Antibody Action

• Precipitation of soluble antigens• Agglutination of foreign cells• Neutralization• Enhanced phagocytosis• Complement activation leading to cell lysis• Stimulates inflammation

• The binding of antibodies to antigens to form antigen-antibody complexes is the basis of several antigen disposal mechanisms.

The classical complimentary pathway, resulting in lysis of a target cell

Immunoglobin ClassesImmunoglobin Classes

IgM• 1st response to antigen• Effective in agglutination• Can’t cross placenta

IgG• Most common form• Crosses blood vessels• Crosses placenta

(passive immunity to fetus)

IgA• Secreted from mucus

membranes• Prevents attachment of

bacteria to epithelial surface• In colostrum

IgD• B cell activation• Can’t cross placenta

IgE• Histamine

reactions and allergies

Overview of Immune System Responses

T Cells

• Mature in thymus• Involved in cell-mediated immunity• Activated when another cell

presents antigen to them• Several types of T cells: cytoxic T

cells, helper T cells, suppressor T cells, and memory T cells

• There are two main types of T cells, and each responds to one class of MHC molecule.– Cytotoxic T cells (TC) have antigen receptors

that bind to protein fragments displayed by the body’s class I MHC molecules.

– Helper T cells (TH) have receptors that bind to peptides displayed by the body’s class II MHC molecules.

T Cells

Cytotoxic T Cell

perforin

pores in target cell

Helper T Cells

interleukin 1macrophage

helper T cell

bacteriumbacterialantigens

T cell receptor

The central role of helper T cells

• The central role in Helper T cells in an infected cell

–T-independent antigens• T cells activated by binding to certain

antigens• No memory cells generated• Weaker response than t-dependent

–T-dependent antigens• Most antigens require co-stimulation to

evoke a B-cell response• Antibody production stimulated with help

from TH

• Most antigens are t-dependent

• T-dependent antigens- can trigger a humoral immune response by B cells only with the participation of helper T cells.

Tissue/Organ Transplants

• Major Histocomatibility Complex (MHC)- Bone marrow- Organs

• Malfunctions of the immune system can produce effects ranging from the minor inconvenience of some allergies to the serious and often fatal consequences of certain autoimmune and immunodeficiency diseases.

Abnormal immune function can lead to disease

Abnormal Immune Function

• Autoimmune Disease• Allergy• Immunodeficiency

Autoimmune Disease• Rheumatoid arthritis• Type I Diabetes• MS• Lupis• Crohn’s disease• Grave’s disease

ABO Blood Types

PhenotypePhenotype GenotypeGenotypeOO i ii iAA I I A A I I AA or I or I A A

iiBB I I B B I I BB or I or I B B

iiABAB I I A A I I BB

Type A

ABO Blood TypesABO Blood Types

Produces Produces anti-B anti-B antibodiesantibodies

b

b

b

b

b

b

b

b

Type B

ABO Blood TypesABO Blood Types

Produces Produces anti-A anti-A antibodiesantibodies

a

a

a

a

a

a aa

aa

Type AB

ABO Blood TypesABO Blood Types

Produces neither anti-A nor anti-B antibodies

Type O

ABO Blood TypesABO Blood Types

Produces Produces both anti-A both anti-A and anti-B and anti-B antibodiesantibodies

a

a

a

a

a

aa

a

a a

b

b

b

b

b

b

b

b

Rh Factor and

Pregnancy

RH- indicates no proteinRH+ indicates protein

15% of population is RH-

Rh Factor and

Pregnancy

Rh+ mother w/Rh- baby– no problemRh- mother w/Rh+ baby– problemRh- mother w/Rh- father– no problemRh- mother w/Rh- baby-- no problem

RhoGAM used @ 28 weeks

Allergy (Immune Hypersensitivity)

• Hypersensitive response to certain environmental allergens

• Food, pollen, pet dander, asthma, bee sting

• Anaphylactic shock - epinephrine

• Mast cells, IgE, and the allergic response.

AIDS

Acquired Immunodeficiency Syndrome

HIV (virus) attacks T-cells

Weakens or eliminates immune system

Susceptible to many fatal diseases

Problems

• Transmission of HIV requires the transfer of body fluids containing infected cells, such as semen or blood, from person to person.– Unprotected sex – Nonsterile needles – HIV transmission among heterosexuals is

rapidly increasing as a result of unprotected sex with infected partners.

– HIV in Africa and Asia- primarily by heterosexual sex

AIDS• In 1983, a retrovirus, now called human

immunodeficiency virus (HIV), had been identified as the causative agent of AIDS.

• With the AIDS mortality close to 100%, HIV is the most lethal pathogen ever encountered.– Molecular studies reveal that the virus probably

evolved from another HIV-like virus in chimpanzees in central Africa and appeared in humans sometimes between 1915 and 1940.• These first rare cases of infection and AIDS went

unrecognized.

AIDS

AIDS

• HIV Testing:– The HIV antibody test has be used to screen

all blood supplies in the U.S. since 1985.• May take weeks or months before anti-HIV

antibodies become detectable.- Drug treatment available- Best prevention is education and protected sex