T-cells, Effector Functions, and the MHC (Timothy Tree) PDF
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King's College London
Tim Tree
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Summary
This document is a set of lecture notes covering T-cell immunity, including diagrams, and various aspects of MHC molecules, as well as T-cell responses and activation. The notes are presented in a clear, organized manner. The structure provides a comprehensive look at cytotoxic and helper T-cell functions.
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Immunology Roadmap LECTURE 2 Innate Immune Protection LECTURE 3 Helen Collins Antibody, Lymphocytes & Diversity Deborah LECTURES 4 &5 Dunn-Walters T cel...
Immunology Roadmap LECTURE 2 Innate Immune Protection LECTURE 3 Helen Collins Antibody, Lymphocytes & Diversity Deborah LECTURES 4 &5 Dunn-Walters T cells, MHC, Tolerance Tim Tree T cells, effector functions and the MHC Dr Tim Tree Department of Immunobiology Faculty of Life Sciences & Medicine 2 Photo – Jon Rawlingson 3 Topics Peptides are displayed by cells in the context of highly polymorphic MHC molecules T cells recognise peptides with their T cell receptors Activation of CD4 T cells requires two signals CD8 T cells are cytotoxic cells that can kill target cells Activated CD4 cells can differentiate into different kinds of effector T cells with different functions. 4 T cell antigen recognition Peptides are displayed by cells in the context of highly polymorphic MHC molecules Structure/function MHC II ab Hetrodimer of MHC molecules Expressed on MHC I specialized antigen Associates with presenting cells: b2 microglobulin Monocytes Endogenously Macrophages expressed on all Dendritic cells nucleated cells B lymphocytes 8-15 amino acids 9 10 Sources of peptides loaded into MHC class I and II MHC class I virus virus MHC class II ntigen Genes encoding MHC class I and II Genes of the MHC are highly polymorphic B7 B 14 Polymorphic residues 17 T cells recognise peptides with their T cell receptors 18 19 T cells are defined by expression of the T cell receptor T cells are defined Membrane bound by expression of hetrodimer the T cell receptor Two chains joined by disulphide bonds Two subtypes ab and gd Consist of variable and constant domains TCR genes undergo rearrangements from germline before translation 50 50 2 50 13 1 2 22 50 50 2 50 13 1 2 23 50 75 2 70 13 24 TCR MHC 25 TCR MHC 26 Two main classes of ab T cell CD8+ T cell CD8 TCR MHC I Two main classes of ab T cell CD8+ CD4+ T cell T cell CD8 TCR CD4 TCR MHC I MHC II Summary - Two main classes of ab T cell CD8+ CD4+ T cell T cell CD8 TCR CD4 TCR MHC I MHC II Activation of T cells requires two signals 30 T cell responses: 2 steps to activation TCR Signal 1 MHC Signal 1 TCRs Signal 1 TCRs Signal 2: ‘co-stimulation’ T cell responses: 2 steps to activation Activation of T cell division production of cytokines CD28 TCR Signal 1 Signal 2: ‘co-stimulation’ CD86 MHC Co-stimulatory molecules upregulated on APC by ‘danger signals’ infection inflammation CD8 T cells kill virus infected or cancerous cells 36 CD8+ T cells: cytotoxic lymphocytes (CTL) CD8+ T cell Killing Virally infected cell CD8+ T cells: cytotoxic lymphocytes (CTL) CD8+ T cell Killing Virally infected cell Cytotoxic T cells killing cervical cancer cells This video was made by Tom Hickin - with help from Claudia Nunes and Richard Stanton - as part of his CUROP project at Cardiff University over the course of 15-16 hours. https://www.youtube.com/watch?v=IDvUB z_zQsc Activated CD4 cells can differentiate into different kinds of effector T cells with distinct functions 42 CD4+ T cells: differentiation of helper lymphocytes naïve CD4+ T cell CD4+ T cells: differentiation of helper lymphocytes naïve CD4+ T cell IL-17 IFN-g IL-4 IL-21 TGF-b IL-2 IL-13 IL-22 IL-10 CD4+ CD4+ CD4+ CD4+ Th1 Th2 Th17 Treg CD4+ Th1 Help Help IFN-γ IL-2 CD8+ T cell CD8+ T cell Macrophage CD8+ T cell APC 45 Th2 cells provide help for B cells CD4+ Th2 Help Cytokines produced: IL-2, IL-4 IL-5, IL-13 B cell Th17 help fight extracellular pathogens Help Epithelium/Fibroblasts CD4+ Th17 Attract Cytokines produced: IL-17, IL-21 IL-22 Neutrophil Treg down-regulate immune responses Suppress stimulatory activity of APC TGF-b Suppress proliferation of IL-10 responder cells Cell-cell contact CD4+ Suppress cytokine Treg production of responder cells Suppress antibody production from B cells Suppress functions of NK & NKT cells Topics T cells recognise peptides with their T cell receptors Peptides are displayed by cells in the context of highly polymorphic MHC molecules Activation of T cells requires two signals CD8 T cells are cytotoxic cells that can kill target cells Activated CD4 cells can differentiate into different kinds of effector T cells with different functions. 49
