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MMI188 Lec 6 & 7

MMI188 Lec 6 & 7 - T Cell-Mediated Immunity...

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T Cell-Mediated Immunity Lectures 6 and 11 Chapter 8 MMI 188 Human Immunology José V. Torres, Ph.D. Professor Medical Microbiology and Immunology School of Medicine University of California at Davis [email protected]
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Activation of Naïve T cells •Meet specific antigen in secondary lymphoid tissues •Undergo clonal expansion •Differentiate into effector T cells •Effector T cells migrate to sites of infection •Antigen stimulates effector T cells to function Three Kinds of Effector T Cells: Cytotoxic CD8 T cells TH1 CD4 T cells TH2 CD4 T cells
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Naive T lymphocytes : T cells that have not yet been stimulated by antigen Recirculate through peripheral lymphoid organs - lymph nodes - L-selectin binds to ligand on high endothelial venules Express TCR, but do not engage in effector functions (cytokine production, cytolysis )
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Effector T lymphocytes : T cells that have differentiated in response to antigen Perform functions required to eliminate pathogens/antigens - cytokine production (helper T cells) - cytolysis (cytotoxic T cells) Migrate to peripheral sites of infection or antigen entry
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Memory T lymphocytes : T cells that have differentiated in response to antigen - are long lived - are functionally silent Capable of mounting enhanced responses to antigen challenge Migrate to lymphoid tissues and peripheral sites of antigen entry Survive without antigen recognition
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Dendritic Cells •pick up antigens in tissues •migrate to peripheral lymphoid organs •present antigens to naïve T cells In Tissues: Immature DCs In Lymph Nodes: Mature or Activated DCs
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Dendritic Cells change functions after taking antigens from infected tissues to secondary lymphoid tissues.
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Dendritic cells use several pathways to process and present protein antigens
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Activation of Naive T Cells Antigen-presenting cells in secondary lymphoid tissues.
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Naïve T cells enter from blood and lymph
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Homing of naïve T cells to secondary lymphoid tissues cell surface molecules cell adhesion molecules – Selectins Vascular addressins – Integrins Immunoglobulin superfamily Main Players: – L-selectin on naïve T cell – CD34 and GlyCAM-1 on high endothelial venules
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Naïve T Cells Enter Lymph Nodes LFA-1 (integrin on T cell) ICAM-1 and -2 (immunoglobulin superfamily members on vascular endothelium) CCL21 (chemokine)
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Functions of T Cell Integrins Adhesion of T cells to APCs T cell activation Binding of T cells to endothelium T cell migration Ligands for integrins are induced on APCs and endothelial cells by inflammatory cytokines and microbes promote T cell responses to infectious agents Affinity of integrins for their ligands is increased by: chemokines (rapid response during inflammation) TCR ligation (amplifies response to antigens on APCs)
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Integrins: LFA-1 (CD11a/CD18) Binds ICAM-1, ICAM-2, ICAM-3 Promotes adhesion and cytoskeletal reorganization during T cell activation Enhances “signal 1” through promotion of stable TCR:MHC interactions
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