Adaptive Immune Response Day 2. The Adaptive Immune Response

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1 Adaptive Immune Response Day 2 Chapter 16 The Adaptive Immune Response 1

2 The B cell receptor vs. the T cell receptor. The B cell receptor vs. the T cell receptor. 2

3 Which T cells have CD4 and which have CD8? Regulatory T cell 3

4 The role of dendritic cells In the tissues: antigen-capturing Activation of T Cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules Migrate to secondary lymphoid organs Co-stimulatory molecules expressed when danger is sensed Activation of T Cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by The role of dendritic cells BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Migrate to secondary lymphoid organs Activates naïve T cell Co-stimulatory molecules expressed when danger is sensed 4

5 The role of dendritic cells In the tissues: antigen-capturing Activation of T Cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by BOTH MHC Class I AND MHC Class II molecules Migrate to secondary lymphoid organs Naïve T cell becomes unresponsive Co-stimulatory molecules expressed when danger is sensed Activation of T Cells In secondary lymphoid organs: antigenpresenting to naïve T cells; antigen presented by The role of dendritic cells BOTH MHC Class I AND MHC Class II molecules In the tissues: antigen-capturing Migrate to secondary lymphoid organs Activates naïve T cell Co-stimulatory molecules expressed when danger is sensed 5

6 Functions of T C (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

7 Functions of T C (CD8 + ) Cells Functions of T H (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

8 Functions of T H (CD4 + ) Cells B cell activation (B cell as the APC) Multiple types - T H 1, T H 2 and others Functions of T H (CD4 + ) Cells B cell activation (B cell as the APC) Antigen represents material that the B cell s receptor has recognized 8

9 Functions of T H (CD4 + ) Cells B cell activation (B cell as the APC) Antigen represents material that the B cell s receptor has recognized T H 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 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

10 Functions of T H (CD4 + ) Cells Macrophage activation (macrophage as the APC) Presented peptides are parts of material that the phagocyte has engulfed T H cell: directs cytokines to that macrophage (activating it) secretes cytokines that stimulate activated cytotoxic T cells Review 10

11 11

12 Figure 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 billion naïve B cells, recognizing ~100 million different epitopes! 12

13 Lymphocyte Development Generation of Diversity - B cells as an example (same principles apply to T cells) ~1/2 billion naïve B cells, recognizing ~100 million different epitopes! gene 1 antibody (B cell receptor) 1 gene 2 antibody (B cell receptor) 2 gene 3 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

14 V3 D1 J2 V (variable), D (diversity), J (joining) V3 D1 J2 V (variable), D (diversity), J (joining) 14

15 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

16 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

17 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

18 Natural Killer (NK) Cells Kill cells bound by antibody Natural Killer (NK) Cells Kill cells bound by antibody Kills self cells that t do not have MHC Class I on their surface (but should) 18

19 MHC Molecules Polygenic MHC Class I molecules, 3 genes Polymorphic Co-dominant 19

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