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6/1/2011 Adaptive Immune Response Day 2 Chapter 16 The Adaptive Immune Response 1 6/1/2011 The B cell receptor vs. the T cell receptor. The B cell receptor vs. the T cell receptor. 2 6/1/2011 Which T cells have CD4 and which have CD8? Regulatory T cell 3 6/1/2011 Activation of T Cells The role of dendritic cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Migrate to secondary lymphoid organs Co-stimulatory molecules expressed when “danger” is sensed Activation of T Cells The role of dendritic cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Activates naïve T cell Migrate to secondary lymphoid organs Co-stimulatory molecules expressed when “danger” is sensed 4 6/1/2011 Activation of T Cells The role of dendritic cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Naïve T cell becomes unresponsive Migrate to secondary lymphoid organs Co-stimulatory molecules expressed when “danger” is sensed Activation of T Cells The role of dendritic cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Activates naïve T cell Migrate to secondary lymphoid organs Co-stimulatory molecules expressed when “danger” is sensed 5 6/1/2011 Functions of TC (CD8+) Cells •Induce apoptosis in “corrupt” self cells (ex. virally-infected) •Recognize antigen presented by Major Histocompatibility Complex (MHC) Class I •Found on all nucleated cells •Endogenous proteins (i.e. made by the cell) are presented •Also secrete cytokines; some increase surveillance of neighboring cells (↑MHC Class I expression) 6 6/1/2011 Functions of TC (CD8+) Cells Functions of TH (CD4+) Cells “Helps” other cells (operations commander); produces various cytokines that activate presenting cell and direct other cells Recognizes antigen presented by Major Histocompatibility Complex (MHC) Class II Exogenous proteins (i.e. those that have been taken up by the cell) are presented Found on antigen-presenting cells (macrophages, B cells….and dendritic cells) 7 6/1/2011 Functions of TH (CD4+) Cells B cell activation (B cell as the APC) Multiple types - TH1, TH2 and others Functions of TH (CD4+) Cells B cell activation (B cell as the APC) Antigen represents material that the B cell’s receptor has recognized 8 6/1/2011 Functions of TH (CD4+) Cells B cell activation (B cell as the APC) Antigen represents material that the B cell’s receptor has recognized TH cell directs cytokines to that B cell, activating it/enabling it to: •Multiply and differentiate to form antibody-secreting plasma cells •Produce memory cells •Undergo class switching Note: T-independent T independent antigens, generally polysaccharides, can activate B cells without T cell help. Children < 2 yo have weak response Ab are often primarily IgM T-independent antigens 9 6/1/2011 Functions of TH (CD4+) Cells Macrophage activation (macrophage as the APC) Presented peptides are parts of material that the phagocyte has engulfed TH cell: •directs directs cytokines to that macrophage (activating it) •secretes cytokines that stimulate activated cytotoxic T cells Review 10 6/1/2011 11 6/1/2011 Figure 16.21 The Big Picture Presented step-by-step Lymphocyte Development Generation of Diversity - B cells as an example (same principles apply to T cells) ~1/2 1/2 billi billion naïve ï B cells, ll recognizing ~100 million different epitopes! 12 6/1/2011 Lymphocyte Development Generation of Diversity - B cells as an example (same principles apply to T cells) ~1/2 1/2 billi billion naïve ï B cells, ll recognizing ~100 million different epitopes! gene 1 gene 2 gene 3 antibody (B cell receptor) 1 antibody (B cell receptor) 2 antibody (B cell receptor) 3 Lymphocyte Development Generation of Diversity - B cells as an example (same principles apply to T cells) Concept will be shown shortly 13 6/1/2011 V3 D1 J2 V (variable), D (diversity), J (joining) V3 D1 J2 V (variable), D (diversity), J (joining) 14 6/1/2011 V3 D1 J2 Rearrangement of DNA (loss of DNA) V (variable), D (diversity), J (joining) Imprecise joining deletions/insertions Combinatorial associations heavy chain/light chain V3 D1 J2 Rearrangement of DNA (loss of DNA) V (variable), D (diversity), J (joining) Imprecise joining deletions/insertions Combinatorial associations heavy chain/light chain 15 6/1/2011 V3 D1 J2 Rearrangement of DNA (loss of DNA) V (variable), D (diversity), J (joining) Imprecise joining deletions/insertions Combinatorial associations heavy chain/light chain Rearrangement of DNA (loss of DNA) V (variable), D (diversity), J (joining) Imprecise joining deletions/insertions Combinatorial associations heavy chain/light chain 16 6/1/2011 Lymphocyte Development Positive and negative selection of self-reactive T cells (in thymus) Positive selection - cells that recognize no material undergo apoptosis destroys those that don’t recognize MHC molecules Negative selection - cells that strongly recognize material undergo apoptosis (or become regulatory T cells) 17 6/1/2011 Natural Killer (NK) Cells Kill cells bound by antibody Natural Killer (NK) Cells Kill cells bound by antibody Kill ““self” Kills lf” cells ll th thatt do d nott have h MHC Cl Class I on th their i surface f (b t should) (but h ld) 18 6/1/2011 MHC Molecules Polygenic MHC Class I molecules, 3 genes Polymorphic y p Co-dominant 19