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Immune System Animals have various means of defense against pathogens—agents that cause disease. Defense systems are based on the recognition of self (one’s own) and nonself (foreign) molecules. Two general types of defense mechanisms: Nonspecific defenses: protect against anything & everything (aka Innate) Specific defenses: aimed at specific pathogens (aka Adaptive) Non-Specific Immunity Barriers: skin mucous membranes cilia & mucus normal flora phagocytosis by macrophages inflammation Blood plasma + RBCs + WBCs + platelets transport for both non-specific and specific Lymph derived from blood; returns fluid from tissue to circulation nodes- cells of the immune system reside here and check fluid for pathogens Red and white blood cells originate from pluripotent stem cells in the bone marrow. These cells constantly divide and can differentiate into a variety of blood cells. http://www.youtube.com/watch?v=I_xh-bkiv_c&feature=related Specific Immunity Antibodies are proteins that bind to substances identified as nonself. Secreted by B cells. T cell receptors are integral membrane proteins, recognize and bind nonself molecules on other cells. Major histocompatibility complex (MHC): on the surface of most mammalian cells. They are selfidentifying labels. Antigens: protein or part of protein-flag = not me T cell receptors and antibodies bind to specific nonself molecules (antigens). Specific sites on the antigens are called antigenic determinants or epitopes. The specific immune system has four key traits: • Specificity • Diversity—response to a wide variety of pathogens • Ability to distinguish self from nonself • Memory Humoral vs. Cellular Response Antibody reacts to Antigen in blood, lymph & tissue fluids Triggers B cells to clone itself plasma cells make Antibody that binds to pathogen memory cells-perpetuate clone & reduce response time at 2nd exposure T cell receptor recognizes Antigen + MHC (me signal) Triggers T cells to clone itself T-cytotoxic –destroys cells with MHC1 + antigen T-helper-alerted by MHC2 + antigen-stimulates B cells to proliferate T-suppressor-turn off response Figure 24.7A Primary immune response Secondary immune response 2 1 B cells with different antigen receptors Antigen molecules Antigen receptor on the cell surface Antibody molecules 3 First exposure to the antigen Cell activation: growth, division, and differentiation Antigen molecules Antibody molecules 4 6 Second exposure 5 to the same antigen First clone Endoplasmic reticulum Plasma (effector) cells secreting antibodies Second clone Clone of plasma (effector) cells secreting antibodies Memory cells Clone of memory cells Figure 24.7A_s1 Primary immune response 1 B cells with different antigen receptors Antigen receptor on the cell surface Figure 24.7A_s2 Primary immune response 1 B cells with different antigen receptors Antigen receptor on the cell surface 2 Antigen molecules Figure 24.7A_s3 Primary immune response 1 B cells with different antigen receptors Antigen receptor on the cell surface 2 Antigen molecules 3 Cell activation: growth, division, and differentiation First exposure to the antigen Figure 24.7A_s4 Primary immune response 1 B cells with different antigen receptors Antigen receptor on the cell surface 2 Antigen molecules 3 First exposure to the antigen Cell activation: growth, division, and differentiation Antibody molecules 4 5 First clone Endoplasmic reticulum Plasma (effector) cells secreting antibodies Memory cells Figure 24.7A_s5 Antigen molecules 6 Memory cells Second exposure to the same antigen Figure 24.7A_s6 Secondary immune response Antibody molecules Antigen molecules 6 Memory cells Second exposure to the same antigen Clone of plasma (effector) cells secreting antibodies Second clone Clone of memory cells Figure 24.7B Antibody concentration Second exposure to antigen X, first exposure to antigen Y Secondary immune response to antigen X First exposure to antigen X Primary immune response to antigen X Antibodies to Y Antibodies to X 0 7 14 21 Primary immune response to antigen Y 35 28 Time (days) 42 49 56 Figure 24.9 Binding of antibodies to antigens inactivates antigens by Neutralization (blocks viral binding sites; coats bacteria) Virus Agglutination of microbes Precipitation of dissolved antigens Activation of the complement system Complement molecule Bacteria Antigen molecules Bacterium Foreign cell Enhances Leads to Phagocytosis Cell lysis Macrophage Hole Humoral vs. Cellular Response Antibody reacts to Antigen in blood, lymph & tissue fluids Triggers B cells to clone itself plasma cells make Antibody that binds to pathogen memory cells-perpetuate clone & reduce response time at 2nd exposure T cell receptor recognizes Antigen + MHC (me signal) Triggers T cells to clone itself T-cytotoxic –destroys cells with MHC1 + antigen T-helper-alerted by MHC2 + antigen-stimulates B cells to proliferate T-suppressor-turn off response Figure 24.11 Phagocytic cell (yellow) engulfing a foreign cell Self-nonself complex Macrophage Microbe B cell T cell receptor Interleukin-2 stimulates cell division 5 3 1 2 Helper T cell 4 6 7 Interleukin-2 activates B cells and other T cells Self protein Antigen from the microbe (nonself molecule) Antigen-presenting cell Interleukin-1 stimulates the helper T cell Binding Binding site for the self protein site for the antigen Humoral immune response (secretion of antibodies by plasma cells) Cytotoxic T cell Cell-mediated immune response (attack on infected cells) Figure 24.11_1 Self-nonself complex Macrophage Microbe 3 1 2 Self protein Antigen from the microbe (nonself molecule) Antigen-presenting cell Figure 24.11_2 Self-nonself complex B cell T cell receptor Interleukin-2 stimulates cell division 5 3 2 4 Antigenpresenting cell Helper T cell 6 7 Interleukin-2 activates B cells and other T cells Binding Cytotoxic site for the T cell self protein Interleukin-1 stimulates the helper T cell Binding site for the antigen Figure 24.12_s1 1 A cytotoxic T cell binds to an infected cell. Self-nonself complex Infected cell Perforin molecule Foreign antigen Cytotoxic T cell Figure 24.12_s2 1 A cytotoxic T cell binds to an infected cell. Self-nonself complex Infected cell Perforin molecule 2 Perforin makes holes in the infected cell’s membrane, and an enzyme that promotes apoptosis enters. A hole forming Foreign antigen Cytotoxic T cell Enzymes that promote apoptosis Figure 24.12_s3 1 A cytotoxic T cell binds to an infected cell. Self-nonself complex Infected cell Perforin molecule 2 Perforin makes holes in the infected cell’s membrane, and an enzyme that promotes apoptosis enters. A hole forming Foreign antigen Cytotoxic T cell Enzymes that promote apoptosis 3 The infected cell is destroyed. Problems • Allergy-hypersensitive immune repsonse – stimulates release of histamine b/c of antigenantibody interaction (immediate response) – T cell response initiated (delayed response) • Autoimmune – fail to destroy antibody producing cell that matches to self antigens – virus antigen resembles self antigen – T cells recognize antigen (non-self) that has a portion similar to self antigen Figure 24.17 Sensitization: Initial exposure to an allergen Later exposure to the same allergen B cell (plasma cell) Mast cell Antigenic determinant 1 An allergen (pollen grain) enters the bloodstream. 2 B cells make antibodies. Histamine 3 Antibodies attach to a mast cell. 4 The allergen binds to antibodies on a mast cell. 5 Histamine is released, causing allergy symptoms.