Chapter 43:The Body’s Defenses

How does your body protect you from invaders?

Immune System Review

Microorganism/Microbe

Pathogen

Antibiotic

Antibody

Antigen

Key Concepts

3 Lines of Defense

Innate vs. Acquired immunityPhagocytes, Lymphocytes, Antibodies, etc…

Humoral vs. Cell-Mediated immunity

Distinguishing self from non-self

Tissue transplantation

Immune Diseases/Disorders

Using HIV to treat Cancer??

http://abcnews.go.com/WNT/video/doctors-hiv-treat-cancer-17929437

What do you think?

How does your body INITIALLY defend itself from invasion? (1st line – specific or non?)

What happens if the invader gets past the 1st line? (2nd line – specific or nonspecific?)

What about more serious infections? (3rd line)

1st line Defense!!Skin, mucus, cilia, saliva, acids, tears, oils, bacteria, coughing, sneezing, vomiting

Antimicrobial proteins & Lysozymes

Innate vs. Acquired ImmunityInnate Immunity:– Present before exposure; since birth– Includes natural bodily defenses, mother’s

milk, or casual exposure– Broad-range capabilities, non-specific– External defenses:

• skin, mucus membranes, tears

– Internal Phagocytic cells • A.K.A.: “macrophages”; engulf invaders

Innate vs. Acquired Immunity

Acquired Immunity:– Develops only after exposure– Highly microbe-specific… how? – Employ lymphocytes & antibodies

• Involves both Humoral & Cell-Mediated responses

Innate Immunity:Your first line of defense

Phagocytic White Blood Cells

Recognize & bind to carbohydrate markers on foreign cell membranes– Triggers receptor-mediated endocytosis– Engulf & digest pathogens via

Phagocytosis

Types of White Blood Cells

Eosinophils: 1.5% of WBCs; destroy large parasites extracellularly

Natural killer (NK) cells: trigger apoptosis in virus-infected cells & cancer cells

Neutrophils: 60-70% of WBCs; engulf and destroy microbes at infected tissue; short lived

Monocytes: 5% of WBCs; develop into….

Macrophages: “big eaters” enzymatically destroy microbes; can be found in spleen, lymph nodes, and other organs

Leukocyte vs. Lymphocyte

Leukocyte = – White blood cells (WBC’s)

Lymphocyte = – Specific type of WBC that mature and

migrate through the lymphatic system and target specific antigens via antibodies, receptors and toxin release

The Inflammatory Response

“Inflammation” = pain, swelling, fever, redness, itching, and pus

Causes of Inflammation

InjuriesExposure to microbes/pathogensExposure to foreign objects or chemicals (insect bites, stings, medications, etc)Exposure to allergens (pollen, pet dander, foods, etc)Rare: sunlight, temperature, self!

The Inflammatory Response3 Steps:

1. Tissue damage = release of chemical signals~– Mast cells release chemicals known as Histamine &

Prostaglandins that trigger inflammation

2. Dilation increases permeability of capillaries~– Increased blood flow; leukocytes leak out to infected area– Delivery of clotting factors & antimicrobial proteins

3. Phagocytosis of pathogens~– WBC’s engulf microbes or damaged tissue– Fever: leukocyte-released chemicals increase body

temperature

Acquired Immunity:Lymphocytes are the Key Defenders

Specific ImmunityAntigen: – a foreign molecule that elicits a

response from a lymphocyte

Lymphocyctes:– WBC’s that originate from stem cells in

bone marrow– B Cells (mature in bone marrow)– T Cells (mature in thymus)

Antibodies: – antigen-binding immunoglobulin,

produced by B cells

Antigen receptors: – membrane receptors on B and T cells

Ch. 43 Research:

Humoral vs. Cell-mediated Responses

B cells vs. T cells

Memory cells

Clonal selection

Autoimmune disease

T cells vs. B cells

T cells:– Mature in Thymus– Target antigen fragments bound to

MHC molecules on Infected Cells– Part of Cell Mediated Response

B cells:– Mature in Bone Marrow– Target in-tact Antigens– Part of Humoral Response

Humoral vs. Cell-Mediated

Humoral immunity

B cell activation

Production of antibodies

Defend against intact antigens free in the lymph and blood plasma– (bacteria, toxins, and viruses)

Humoral response: B cells

Stimulated by an antigen-presenting macrophage (WBC w/ a germ on it)

Activates Helper T cells

T cells secrete cytokine chemicals that activate B cells

B cells differentiate into memory B cells and antibody-producing plasma cells

Cytokines

Cytokine:– Proteins secreted by phagocytic cells

(macrophages, etc.) and T-helper cells– Activate Lymphocytes (B & T cells)

Humoral Response:

1. B cells activate.

2. Plasma cells secrete antibodies.

3. Antibodies attach to antigens.

4. Antigens agglutinate (stick together) & get disposed.

5. Macrophages phagocytose or lyse the cell.

Cell-mediated immunity

T cells are activated.

T cells bind to and/or lyse infected cells.

Defend against cells infected with bacteria, viruses, fungi, protozoa, parasites, even cancer!

Cell-Mediated

Cell-mediated Response

1) Cell surface molecules expose antigens (foreign proteins).

2) Cytotoxic T cell releases perforin, a protein that forms pores in the target cell membrane.– causes cell lysis and exposes pathogens to

circulating antibodies for disposal

Humoral ResponseCell Mediated Response

In Tact Antigens Antigens on Infected Cells

B Cell Activation T Cell Activation

Secrete antibodies that defend

against pathogens & toxins in

extracellular fluid

Defend against infected cells,

cancer and transplanted

tissues

Clonal SelectionClonal selection: – antigen-driven cloning of lymphocytes

Effector cells: – short-lived cells that combat the antigen initially

Memory cells: – long-lived cells that bear receptors for the antigen

and activate upon subsequent exposure.

Active vs. Passive ImmunityActive: natural exposure to antigens causes one’s own lymphocytes to activate and produce antibodies– May also be acquired by Immunizations

Passive: direct transfer of antibodies through placenta or mother’s milk

HIVHuman Immunodeficiency Virus

Causes AIDS (Acquired Immune Deficiency Virus)

HIV (a retrovirus) attacks helper T cells by binding with their cell receptor (CD4)

This impacts both the Humoral and Cell Mediated responses

Clonal Selection Hypothesis

Each lymphocyte bears one specific type of receptor.

Receptor/antigen binding is required for cell activation.

Activated lymphocytes divide and give rise to cells with identical receptors to the parent.– This is how your immune system “remembers” a

pathogen later!

Clonal Selection Hypothesis

First, those lymphocytes bearing receptors compatible to “self” tissues are destroyed (3)

Second, those bearing receptors that match foreign antigens are activated then cloned (5/6)

Self/Nonself Recognition

Self-tolerance: – Capacity to distinguish self from non-self

molecules

Autoimmune diseases: – Failure of self-tolerance mechanisms– Multiple sclerosis, lupus, rheumatoid arthritis,

insulin-dependent diabetes mellitus, Crohn’s disease

Abnormal immune functionAllergies: – hypersensitive responses to environmental antigens (allergens)– causes dilation and blood vessel permeability– Histamines are released from Mast cells

Autoimmune disease: – multiple sclerosis– Lupus– rheumatoid arthritis– insulin-dependent diabetes mellitus

Immunodeficiency disease: – SCIDS (bubble-boy)– A.I.D.S. (HIV)

Cancer & the Immune System

Tumor cells are targeted by both Cytotoxic T cells and Natural Killer (NK) cells

– How might some tumors escape detection??

Treg research: Article Review

What are “Regulatory T Cells” (Tregs)?

What is their role in immunity?

How might they be linked with cancer?– Article: “Regulatory T cells and tumour

immunity – observations in mice and men” by Gallimore and Godkin, 2007

Major Histocompatibility Complex

Aka: “MHC”

Cell surface proteins that display fragments of antigens or processed proteins on the cell surface

Epitope: – region of antigen surface

recognized by antibodies

Induction of Immune Responses

Primary immune response: – lymphocyte proliferation and differentiation the 1st

time the body is exposed to an antigen

Plasma cells: – antibody-producing B-cells

Secondary immune response: – immune response if the individual is exposed to

the same antigen at a later time~ Immunological memory

Types of ImmunoglobinsIgM: – 1st to circulate; indicates infection; too large to cross

placenta

IgG: – most abundant; crosses walls of blood vessels and placenta;

protects against bacteria, viruses, & toxins; activates complement

IgA: – produced by cells in mucous membranes; prevent

attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration

IgE: – very large; small quantity; releases histamines-allergic

reaction

Antibody-Mediated Antigen Disposal

Neutralization (opsonization): – antibody binds to and blocks antigen activity

Agglutination: – antigen clumping

Precipitation: – cross-linking of soluble antigens

Complement fixation: – lyses viruses and pathogenic cells & activates cell

surface proteins to break down the cell

Immunity in Health & DiseaseActive immunity:– natural: conferred immunity by recovering from disease

– artificial: immunization and vaccination; produces a primary response

Passive immunity: – transfer of immunity from one individual to another

– natural: mother to fetus; breast milk

– artificial: rabies antibodies

ABO & Rh blood groups (antigen presence)