Adaptive (acquired) immunity. Professor Peter Delves University College London
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1 Adaptive (acquired) immunity Professor Peter Delves University College London
2 Haematopoiesis
3 Haematopoiesis Lymphocytes = adaptive response
4 Recognition of pathogens by adaptive cells, i.e. lymphocytes, is highly antigen-specific
5 Lymphocytes need to proliferate to provide enough specific cells to fight the infection
6 Adaptive immunity is characterised by primary and secondary immune responses
7 Adaptive Immunity -Two kinds of lymphocytes: T and B Both exhibit: 1. antigen-specificity 2. immunological memory Adaptive immunity
8 B-cells and T-cells T H and Treg cells
9 The main differences between T and B lymphocytes Antigen receptor Antigen receptor signalling MHC class II (high density) B cells T helper cells T regulatory cells T cytotoxic cells Antibody (BCR) T-cell receptor TCR TCR (TCR) Iga/Igb CD3 CD3 CD CD CD4 or CD8 Neither CD4 (mostly) CD4 (mostly) CD8 (mostly) Foxp
10 Lymphocytes B-cells T-cells
11 B lymphocytes recognise antigen directly and differentiate into antibody-secreting plasma cells B B B B
12 Lymphocytes B-cells T-cells
13 T-cells recognise antigen using the T-cell 2 main types of TCR: receptor (TCR) gd heterodimer ab heterodimer
14 Unlike antibodies (the BCR) that recognise the three dimensional shape of an antigen, the ab T- cell receptor (TCR) recognises antigen that is: a) Processed (into peptides, by proteases) then: b) Presented (by cell surface MHC molecules)
15 Two pathways of antigen processing Endogenous: produces peptides 8-9 amino acids long for presentation by MHC class I Exogenous: produces peptides 15 amino acids long for presentation by MHC class II
16 Processing pathways for presenting antigen to T cells Endogenous Exogenous
17 ab TCR recognises processed antigen presented by MHC
18 Activation of the T-cell requires costimulation Anergy
19 Activation of the T-cell requires costimulation Anergy e.g. Dendritic cell Activation
20 Functional activity of T-cells Proliferate Mediate effector functions Form memory cells
21 Different types of T-cell effector function ab T-cell CD4 Th1 CD4 Th2 CD4 Th17 CD4 Tfh CD4 Treg CD8 Tc Produce/ express IFNg IL-2 TNFb IL-4 IL-5 IL-10 IL-13 IL-17 IL-22 IL-21 ICOS TGFb IL-10 IL-35 Perforin Granzymes FasL Cytokines Primary function Help CTL & macrophages (& some B-cells) Inhibit Th2 Help B-cells Inhibit Th1 Promote inflammation Help germinal center B-cells Suppress immune responses Kill infected cells
22 T helper cell activation of macrophages
23 T helper cell activation of cytotoxic T-cells
24 Cytotoxic T-lymphocytes (CTL)
25 Killing by cytotoxic T-cells Perforin & granzymes
26 Lymphocyte development
27 T-cell development in the thymus CD4 - CD4 + CD8 - CD8 +
28 Lymphocytes need to proliferate to provide enough specific cells to fight the infection
29 Lymphocytes also need to circulate around the body
30 Role of dendritic cells in adaptive immunity
31 Interdigitating dendritic cells Present antigen to T cells Follicular dendritic cells Present antigen to B cells
32 Interdigitating dendritic cells dendritic cells
33 Interdigitating dendritic cells MHC class II + CD80/CD86 + (B7.1/B7.2) Can activate naive T-cells
34
35 Migration and maturation of interdigitating dendritic cells (IDCs)
36 Follicular dendritic cells
37 Follicular dendritic cells MHC class II negative Complement receptor + FcgR + Present antigen to B-cells
38 Comparison of IDC and FDC IDC FDC Developmental Haematopoietic stem cells (HSC) Unknown (not HSC) origin Location Widespread Germinal centres of secondary lymphoid organs MHC class II + - CD80 & CD Endocytose/ (phagocytose) antigen + (+/-) - Antigen presentation Processed antigen Native antigen to T-cells to B-cells
39 Follicular dendritic cell (FDC) surrounded by B lymphocytes in a lymph node germinal centre
40 Follicular dendritic cell (FDC)
41 Follicular dendritic cell (FDC) ICCOSOMES Immune-complex coated bodies
42 Fc receptor C' receptor
43 Fc receptor Antibody C' receptor Antigen
44 Fc receptor Antibody C C' receptor Antigen
45 Fc receptor Antibody C C' receptor B-cell
46 Adaptive immunity summary Based on lymphocytes Memory Specificity
TCR, MHC and coreceptors
Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed
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