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Published byGilbert Horton Modified over 9 years ago
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Immunology molecular medicine 3 Conleth Feighery
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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
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CYTOKINES Cells of the immune system ‘talk’ to each other by producing cytokines - like ‘text messages’ informing cells what their function should be!
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CD4+ T cells - MHC II interaction APC T h cytokines
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CD4+ T cells interact with APC and other cells by releasing cytokines. APC also release cytokines. APC T h cytokines The type of cytokines that are released are crucial to the type of immune response which results
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Cytokine products of cells APC T h IL-1 IL-2 CD28 B7
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Cytokine product of cells APC T h IL-1 IL-2 Cells interact through the production and release of cytokines - these bind to cells and affect their function CD28 B7
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Cytokine products of cells APC T h IL-1 IL-2 Receptors - cytokines bind to specific cell receptors
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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
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IL-1 helps T cell activation APC T h IL-1 produced by APC
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T cell co-stimulation Essential to T cell activation, division and replication
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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
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CD4+ T cells - activation requires 2 signals APC T h CD4 T cell receptor binding to antigen = signal 1 CD28 B7 CD28 binds to B7 = signal 2
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Stimulated T cell - IL-2 produced APC T h CD4 CD28 B7 IL-2 IL-2 receptor IL-2 binds to receptor on cell - causes cell growth, division
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IL-2 required for T cell growth APC T h IL-2 CD28 B7
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CTLA-4 - negative signal APC T h CD4 T cell receptor binding to antigen = signal 1 CTLA-4 B7 CTLA-4 binds to B7 - inhibits stimulation
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T cell cytokines affect B cells T h B IL-4,5,6
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T cell cytokines affect B cells T h B IL-4, IL-5, IL-6 IL-4, 5 and 6 all involved in B cell stimulation and Ig production
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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
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Lymph node - histology Lymphoid follicles
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Interferon gamma helps kill intracellular infections MO T h TB Interferon - gamma IFN- IFN- activates macrophage killing mechanisms
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T cytotoxic cell - recognition of antigen, role of CD8 APC T cytx T cytotoxic cell reacting with virus antigen presented by MHC class I molecule CD8 MHC I Target cell virus
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CD8+ T cells can kill target cells by inserting a ‘perforating hole’ in the cell, through which enzymes enter, damaging the cell APC T cytx TARGET CELL CD8 perforin enzymes
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T cytotoxic cell - cytolytic mechanism APC T cytx Target cell virus Lytic granules perforin Enzymes, water, salts Granules - content perforin, enzymes
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Pattern recognition receptors Various stimuli bind to receptors on APC and influence APC reaction APC TOLL Stimulus
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Pattern recognition receptors Various stimuli bind to receptors on APC and influence APC reaction Different cytokines APC B7 Toll-like receptors Stimulus
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APC –effect on T cell response APC Stimulus TH 1 TH 2 T reg IFN- IL-4 IL-10
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APC - effect on T cell response TH 1 TH 2 T reg IFN- IL-4 IL-10 APC Stimulus
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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
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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
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TCR - alpha, beta chains alpha chain beta chain variable region constant region
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T cell receptor structure Alberts et al.
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TCR - gamma, delta chains gamma chain delta chain variable region constant region
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Immunoglobulin super-family Many molecules in the immune system have an Ig-like structure and hence, belong to the “Ig superfamily”. Alberts et al.
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MHC I and II structure Alberts et al.
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