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Transcript
Immunology molecular medicine 3 Conleth Feighery Learning objectives • T cell binding to APC essential for T cell stimulation • T cell cytokines – determine their effect • APC use pattern recognition receptors • The structure of the T cell receptor CYTOKINES Cells of the immune system ‘talk’ to each other by producing cytokines like ‘text messages’ informing cells what their function should be! CD4+ T cells - MHC II interaction APC Th cytokines CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines. APC Th cytokines The type of cytokines that are released are crucial to the type of immune response which results Cytokine products of cells APC Th CD28 B7 IL-1 IL-2 Cytokine product of cells APC Th CD28 B7 IL-1 IL-2 Cells interact through the production and release of cytokines - these bind to cells and affect their function Cytokine products of cells APC Th IL-1 IL-2 Receptors - cytokines bind to specific cell receptors Cytokines • • • • Small protein molecules c. 20,000 aa Specific types produced by different cells Bind to cells and affect cell function Some are called “interleukins” or IL IL-1 helps T cell activation Th APC IL-1 produced by APC T cell co-stimulation Essential to T cell activation, division and replication Activation of T cells • • • • • Requires 2 signals Signal 1 - TCR, MHC, antigen Signal 2 - CD28 binding to B7 Both signals must be from the same APC ONLY now can T cell proliferation start CD4+ T cells - activation requires 2 signals CD4 APC Th CD28 B7 T cell receptor binding to antigen = signal 1 CD28 binds to B7 = signal 2 Stimulated T cell - IL-2 produced CD4 APC Th IL-2 receptor CD28 B7 IL-2 IL-2 binds to receptor on cell - causes cell growth, division IL-2 required for T cell growth APC Th CD28 B7 IL-2 CTLA-4 - negative signal CD4 APC Th CTLA-4 B7 T cell receptor binding to antigen = signal 1 CTLA-4 binds to B7 - inhibits stimulation T cell cytokines affect B cells B Th IL-4,5,6 T cell cytokines affect B cells B Th IL-4, 5 and 6 all involved in B cell stimulation and Ig production IL-4, IL-5, IL-6 Lymph node - cartoon Alberts et al. T cell activation takes place in lymph node tissue T cell help for B cells takes place in lymph. follicles Lymph node - histology Lymphoid follicles Interferon gamma helps kill intracellular infections MO Th IFN-g activates macrophage killing mechanisms TB Interferon - gamma IFN-g T cytotoxic cell - recognition of antigen, role of CD8 CD8 virus APC T cytx Target cell MHC I T cytotoxic cell reacting with virus antigen presented by MHC class I molecule CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell CD8 TARGET APC CELL T cytx • perforin • enzymes T cytotoxic cell - cytolytic mechanism Lytic granules Granules - content perforin, enzymes virus APC T cytx Target cell Enzymes, water, salts perforin Pattern recognition receptors TOLL Stimulus APC Various stimuli bind to receptors on APC and influence APC reaction Pattern recognition receptors Toll-like receptors Stimulus B7 APC Various stimuli bind to receptors on APC and influence APC reaction Different cytokines APC –effect on T cell response Stimulus APC TH 1 IFN-g TH 2 IL-4 T reg IL-10 APC - effect on T cell response Stimulus APC TH 1 IFN-g TH 2 IL-4 T reg IL-10 Cytokines and T cells • Depending on the antigen, APC may produce different sets of cytokines • These cytokines determine the type of T cell that proliferates • Different types of T cells produce specific sets of cytokines Structure of molecules of IS • • • • T cell receptor or TCR MHC class I MHC class II Antibody molecules Knowledge of these structures is helpful in understanding how immune system functions TCR - alpha, beta chains constant region variable region alpha chain beta chain variable region T cell receptor structure Alberts et al. TCR - gamma, delta chains constant region variable region gamma chain delta chain variable region Immunoglobulin super-family Alberts et al. Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”. MHC I and II structure Alberts et al.
