How do T cells develop? T cells from the bone marrow are selected in the thymus before entering the periphery T cell development in the thymus occurs in a specific order Only 5% of the cells that enter the thymus exit into the periphery!! Naive T cells encounter antigen during their recirculation through secondary lymphoid organs Steps in T cell proliferation Humoral Immunity Cell-mediated Immunity L-selectin and LFA-1 are also involved in T cells homing Activated (effector) T cells express many surface molecules that are important in their function Two signals are required for T cell activation Step 1: The strength of the interaction between APCs and T cells must reach a certain threshold Second signal required - called costimulation B7 binding to CD28; Activated T cells also upregulate the IL-2 receptor (CD25) Not all APCs are equal in terms of ability to present antigen T cell activation can be regulated by CTLA-4, an inhibitory receptor for B7 molecules Once activated, T cells express increased levels of CTLA-4 (CD152). CTLA-4 has a higher affinity than CD28 for B7 molecules and thus binds most or all of the B7 molecules, serving to regulate the proliferative phase of the response. CD40 ligand expression is critical to the ability of CD4+ T cells to activate other cells. The interaction between a B cell and a T cell with specificity for the same antigen is called a cognate interaction Effector mechanisms of CD4+ T cells are the cytokines -transient production -autocrine and paracrine -pleotropic -redundant CD4+ helper T cells are ?classified? based on the types of cytokines they produce Also Th0 - mixture of Th1 and Th2 (IL-2 and IL-4) ; also IL-2 Different antigens trigger distinctly different Th cell subpopulations Th2-type Th1-type Whether a CD4+ T cell becomesTh1 or Th2 type depends on the triggers (cytokines) in their environment Also IL-10 Functions of CD4+ Th1 T cells Cytokines produced: IL-2 - activates T cells, B cells, NK cells, macrophages IFN? - inhibits Th2 cells , stimulates Th1 cells, activates NK cells and macrophages; also upregulation of MHC Class II; production of IgG1 and IgG3 (complement-fixing) Functions of CD4+ Th2 T cells Cytokines produced: IL-4-stimulates B cell growth and differentiation, activates mast cells IL-5 - stimulates B cell growth, mobilizes and activates eosinophils, IL- 6 - stimulates B cells IL-10- inhibits Th1 function, suppresses macrophage function IL-13 - stimulates B cell growth, suppresses macrophage function The balance between Th1 and Th2 determines the outcome of intracellular infections Two types of cell-mediated immune responses against intracellular microbes IFN-? CD8+ cytotoxic T cells (CTLs) Activation of na´ve CD8+ T cells to become cytotoxic effector cells requires more stringent co-stimulation signals (only from dendritic cells) than CD4+ T cells CD8+ cytotoxic T lymphocytes (CTLs) kill infected cells Cell death ? CTL can disengage to kill new target Apoptosis can be induced in either of 2 ways Also perforin How does the T cell response get turned off ??
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