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Host Defenses Immune System Terminology Immunity Antigen (Ag) Specific antibody and lymphocyte response to an antigen A substances that causes the body to produce specific antibodies or sensitized T cells Antibody (Ab) Proteins made in response to an antigen Humoral immunity Involves Ab produced by B cells Cell-mediated immunity Involves T cells Acquired immunity Developed during an individual's lifetime •Naturally acquired active immunity (Resulting from infection) •Naturally acquired passive immunity (Transplacental or via colostrum) •Artificially acquired active immunity (Injection of Ag (vaccination)) •Artificially acquired passive immunity (Injection of Ab) White Blood Cells Antigenic Determinants • • • • • Neutrophils: Basophils: Eosinophils: Monocytes: Phagocytic Produce histamine Toxic to parasites, some phagocytosis Phagocytic as mature macrophages 60-70% of WBCs 0.5-1% of WBCs 2-4% of WBCs 3-8% of WBCs – Fixed macrophages in lungs, liver, bronchi – Wandering macrophages roam tissues • Lymphocytes: Involved in specific immunity 20-25% of WBCs Antibodies recognize and react with antigenic determinants or epitopes. Immunoglobulins (classes of antibodies) Antibody Structure IgG IgM IgA IgD IgE Structure % of serum antibody 80% 5-10% 10-15% Location Blood, lymph, intestine B cell surface, Secretion B cell blood, lymph s (tears, surface saliva, milk) Mast cell and basophil surfaces Half-life in serum 23 days 5 days 3 days 2 days Functions See next slide First Ig Protects produced. mucosal Binds large surfaces microbes; aggulutination Unknown Release of histamines, lysis of parasitic worms 6 days 0.2% 0.002% Antibody Genetics Results of AG-AB Binding VH1 VH2 VL1 VL2 VL3 Chromosome 2 300 Variable genes VH199 VH200 VL299 DH1 VL300 DH2 Chromosome 14 JL1 JL2 JL3 5 Joiner genes DH12 JH2 JH3 4 Joiner genes JH4 1 Constant gene CH Light chain genes 12 Diversity genes JH1 JL4 JL5 CL 200 Variable genes Heavy chain genes 8 Constant gene Clonal Selection Antibody Titer Random deletion and recombination of antibody genes results in one set of VLC Light chain genes and one set of VDJC Heavy chain genes in each B cell. Bone Marrow Stem Cell VL212-J4-C VH189-D1-J3-C VL57-J4-C VL34-J1-C VH198-D17-J3-C VH69-D8-J4-C V188-J5-C VH41-D12-J2-C VL2-J1-C VH99-D10-J3-C 300VL * 5JL = 1500 Light Chains VL256-J5-C VH111-D11-J1-C X 200VH * 12DH * 4 JH = 9600 Heavy chains B cells are genetically identical to all other body cells except they have fewer antibody genes = 14 Million Different B Cells (each produce unique antibody) Provide long-term protection in case body is ever re-infected with same pathogen. The more memory cells, the longer the immunity lasts. Active antibody production during infection T cell-dependent immune response 1. 2a. Macrophage phagocytizes microbe. 2b. B cell with SPECIFIC ANTIBODY binds to free microbial antigen (AG-AB complex). 3a. Macrophage digests microbe (using lysosomes). 4a. Macrophage displays microbial antigen (AG) along with MHC-II protein (AG-MHC complex). Macrophage is now an Antigen Presenting Cell (APC). 5a. Helper T cell with SPECIFIC T CELL RECEPTOR (TCR) binds to specific AG-MHC complex. Macrophage is stimulated to secrete Interleukin-1. 6. Major Histocompatibility Complex Pathogenic microbes infect human body. 3b. B cell ingests AG-AB complex by endocytosis. 4b. B Cell displays microbial antigen (AG) along with MHC-II protein (AG-MHC complex). B Cell is now an Antigen Presenting Cell (APC). Interleukin-1 stimulates T Cell to reproduce many times. 7. T Cell clones differentiate into: • Helper T Cells which have the identical TCR to the T Cell in step 5a (in other words, they recognize and bind to the specific AG-MHC of the infecting microbe). • Memory T Cells which recognize the same AG-MHC but are not active. They circulate and reproduce but die off faster. So eventually, they become depleted. • Cytotoxic T cells which recognize the same antigen. 8a. Cytotoxic T cells bind to infected body cells and release perforins which kill the body cells. This is an especially important defense against viruses. 8b. Helper T cell, which recognizes specific AG-MHC, binds to B cell (from step 4B) which displays the correct AG-MHC. Helper T cell secretes cytokines which stimulate the B cell to reproduce and differentiate. Mom Dad A3 B6 C1 Dp7 Dr8 Dq3 A2 B8 C7 Dp2 Dr15 Dq13 A6 B2 C13 Dp11 Dr10 Dq21 A8 A6 B4 B2 C10 C13 Dp11 Dp1 Dr10 Dr3 Dq16 Dq21 MHC Genotypes of Children A3 B6 C1 Dp7 Dr8 Dq3 A2 B8 C7 Dp2 Dr15 Dq13 A3 B6 C1 Dp7 Dr8 Dq3 A8 A6 B4 B2 C10 C13 Dp11 Dp1 Dr10 Dr3 Dq16 Dq21 A6 B2 C13 Dp11 Dr10 Dq21 A2 B8 C7 Dp2 Dr15 Dq13 A6 B2 C13 Dp11 Dr10 Dq21 A8 A6 B4 B2 C10 C13 Dp11 Dp1 Dr10 Dr3 Dq16 Dq21 9. B Cell clones differentiate into: • Plasma Cells which circulate and secrete large quantities of the specific antibody from step 2b. • Memory B Cells which have the genes to produce the same antibody, but are immunologically inactive. They circulate and reproduce but die off faster. So eventually, they become depleted.