The Body’s Defense Against Disease Unleashing the Fury of the Immune System Cytotoxic T-Cell killing a cancer cell Macrophage engulfing bacteria

Non Specific Defense Mechanisms Innate Immunity The Skin and Mucus Membrane: External Defenses are Physical barriers Perspiration, tears and saliva contain lysozyme, an enzyme that attacks the cell wall of bacteria Gastric Acid destroys proteins in germs by low pH Mucus traps germs

Phagocytes and Natural Killers Internal Defenses Macrophages -long living cells which develop from monocytes and engulf cells which display antigens (foreign protein patterns) Neutrophils -short living phagocytes which usually die after engulfing a germ Natural Killers – type of cytotoxic T-cell that identifies and destroys infected body cells by lysing membranes

Macrophage attacking E. coli

Antimicrobial Proteins Internal Defenses a) Interferon -inhibits the production of viral proteins Makes cancer cells less likely to metastasize Triggers inflammatory response Attracts macrophages b) Complements -group of about 30 proteins which facilitate phagocytosis and lysis of infected membranes

4. Inflammatory Response a) Basophils & Mast Cells release histamine which dilate and increase the permeability of blood vessels Increase blood supply to infected area Causes a leakage of plasma into area Release of leukocytosis inducing factor which stimulates the release of WBC from the bone marrow Chemical signals also attract phagocytes Pyrogens -increase body temperature which facilitates phagocytosis and inhibits bacterial growth

B. The Immune Response Active Vs Passive Immunity Active immunity -the body is stimulated to produce its own antibodies Passive immunity -fetus gets antibodies from mother or antibodies are injected into a patient Duality of the Immune System Humoral immunity -the production of antibodies which circulate as soluble protein in the blood and attack free germs Cell Mediated immunity produces cells which attack infected cells directly

C. The Humoral Immune Response B lymphocytes or B cells are activated by antigens directly or by T lymphocytes Activated B cell begin to produce two other types of cells Memory Cells -survive for long periods of time and proliferate rapidly when exposed to the same antigen Plasma Cells -begin producing as many as 2000 antibodies per second for 4 to 5 days

3. One Method of B Cell Activation T independent antigen (green triangle) binds to the B cell and activates the B cell Activated B cell divides forming memory cell and plasma cells Plasma cells begin production of antibodies B cell Plasma cell Memory cell Antibodies

4. Antibodies constitute a group of proteins called Immunoglobulins Ig

a) Antibody Structure Y shaped molecule composed of 4 polypeptide chains: 2 light (small), 2 heavy chain (larger) All four chains have regions that are constant and regions that are variable The variable regions function as binding sites and are specific to each antigen

b) Types of Immunoglobulins Ig M: Five Y-shaped monomers arranged in a pentameter. Appear in initial antigen exposure and trigger agglutination. Ig G: Y-shaped monomer. Most abundant. Readily crosses blood vessels. Binds to antigen and activates compliment

Ig A: Dimer of 2 Y-shaped monomers Ig A: Dimer of 2 Y-shaped monomers. Abundant in mucus membrane, saliva & tears Ig D: Y-shaped monomer bound to B cells. Used as a receptor for T independent antigens Ig E: Y-shaped monomer on basophils and mast cells. Antigen binding stimulates release of histamines

c) How Antibodies Work: Neutralization -block viral and bacterial binding sites

2) Agglutination -attach and immobilize germs forming clumps which are then engulfed by macrophages Antibodies Germ

3) Activate compliment proteins which lyse cell membranes

5. Activation of B Cells by Macrophages When a macrophage engulfs a germ, partially digest antigens are displayed on its membrane The antigens are mounted of Major Histocompatability complexes (MHC): a series of glycoproteins which allow the body to recognize self from non-self

c) The macrophage is now an Antigen Presenting Cell or APC and it attracts specific Helper T Cells d) Helper T Cells bind with the APC and are activated by il-1. TH cells then release il-2 which: Causes TH cells to reproduce and stimulates Killer T cells Activates B Cells

e) B cells attach to T cells and begin to make plasma cells (which produce antibodies) and memory cells Activated B cell Antibodies

6. T dependent and T independent Antigens T dependent antigens -only stimulate the production of antibodies with the help of T cell T independent Antigens -can bind directly with Ig D appearing on the B cell and stimulate the B cell without T cells

C. Cell Mediated Responses T cells cannot be activated by free antigens in the body fluid MHC -antigen complexes on APCs attract T cell. T cells bind with the complex and trigger Activation of B cells The production of more Helper T cells The production of Cytotoxic T cells (T killers)

3. T Helper Cells are able to stimulate other lymphocytes by sending and receiving cytokines When T Helpers bind to APCs, the APC releases interleukin 1 This causes the T Helper to release interleukin 2 which causes T Helpers to divide and helps activate B Cells and Cytotoxic T cell

4. Cytotoxic T-Cells (T-Killers) are cells which destroy cells with antigens directly Attach to cells with antigens Release perforin, a protein which will lyse cell membranes This kills the cell the cell and prevents it from reproducing new viruses

Cytotoxic T-Cell killing a cancer cell Perforin vessicles Ruptured membrane Cytotoxic T cell