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The Humoral (B cell) Immune Response Linked Recognition Th2 focus their activating cytokines… (Talin binds to actin microfilaments) Antibody isotype switching: Switch transcripts produced on both chromosomes Where do activated B cells and activated helper T cells get together? (trapping) Freq of lympho’s specific for given Ag is 1/1,000,000 Some B cells in the primary focus become plasma cells Other B cells form germinal centers •Somatic hypermut’n •Affinity maturation •Isotype switching FDCs attract B cells to germinal centers B cells undergo somatic hypermutation, selection (+ and -) •1 bp change per 1000 bp per cell division •V regions 360 bp •¾ of changes is an altered aa •½ of B cells gets changed BCR B cell survival in Germinal Centers • Cross-linking of BCRs by Ag – Ag on FDCs??? – Pathogens multiplying in lymphoid tissue??? • CD40 ligation by T cell CD40L • Other signals? – Eg. TNF family cytokines Thymus-independent 1 Ags (TI-1) •Induce all B cell division •Called B cell mitogens •Eg. LPS •Unable to induce isotype switching(?), affinity maturation, or memory cells TI-2 Ags •Activate only mature B cells •Repeating epitopes •IgM, sometimes IgG •Eg. Bacterial capsular polysaccharides, pyogenic bacteria Transcytosis of IgA •Gut, lungs, tears, saliva, mammary •Poly-Ig Rc •Protection of epithelial surfaces IgG and IgA can inhibit viral infectivity IgM has two conformations Ag-bound Ab binds FcRc with high avidity Fc and C3b Rc’s on phagocytes Schistomsome larva attacked by eosinophils ADCC = antibodydependent cellmediated cytotoxicity IgE pre-loaded on mast cells Cross-linking causes mediator release •Prostaglandin D2, leukotriene C4, TNF-alpha