Janeway Murphy Travers Walport Immunobiology 7 Chapter 9 The Humoral Immune Response Copyright Garland Science 2008 Tim Worbs Institute of Immunology Hannover Medical School 1
The course of a typical antibody response 2
Antibody responses are primarily directed against extracellular pathogens and their toxic products 3
Antibodies participate in host defense by three principal modes of action 4
The signalling requirements during B cell activation are determined by the nature of the antigen TD TI-1 TI-2 5
The B cell receptor (BCR) complex is formed by membrane-bound Ig and invariant accessory chains 6
The activation of B cells requires cross-linking of BCR complexes by multivalent antigens 7
Clustering with the B cell co-receptor complex augments BCR signalling 8
B cell activation by Thymus-independent (TI-1 and TI-2) antigens 9
Characteristic properties of Thymus-dependent (TD) and Thymus-independent (TI-1 and TI-2) antigens 10
CD5 + B1 cells and marginal zone B cells prominently contribute to the antibody response against TI-2 antigens 11
Armed helper T cells stimulate the proliferation and then the differentiation of TD antigen-binding B cells 12
B cells and helper T cells must recognize epitopes of the same molecular complex linked recognition 13
Protein antigens attached to polysaccharide antigens allow T cells to help polysaccharide-specific B cells 14
Helper T cells deliver membrane-bound stimuli and secreted cytokines in a polarized fashion to individual B cells 15
Antigen-binding B cells encounter helper T cells at the border between T cell and B cell zones of secondary lymphoid organs spleen 16
Antigen-binding B cells encounter helper T cells at the border between T cell and B cell zones of secondary lymphoid organs lymph node 17
Plasma cells secrete antibody at a high rate but can no longer respond to antigen or T cell help 18
The differentiation of resting B cells into plasmablasts and plasma cells is accompanied by profound morphological changes 19
Plasma cells generated in primary foci and germinal centers migrate to medullary cords, splenic red pulp and bone marrow 20
IgG and IgA secreting plasma cells are dispersed within medullary cords, splenic red pulp and bone marrow medullary cords (short-lived days) IgG IgA bone marrow (long-lived month to years) κ light chain λ light chain 21
The germinal center is a specialized microenvironment for B cell proliferation, somatic hypermutation and affinity maturation Ki67 FDC CD4 22
Activated B cells undergo rounds of mutation and selection for higher-affinity immunoglobulins within germinal centers 23
The germinal center reaction results in the generation of plasma cells and memory B cells expressing high-affinity immunoglobulins 24
Somatic hypermutation introduces mutations into the rearranged immunoglobulin variable region 25
The molecular structure of immunoglobulins 26
The complementary-determining regions (CDRs) are hypervariable regions of heavy and light chain V domains 27
The hypervariable amino acid sequences of the CDRs form the antigen-binding site of the folded V domains 28
Antibodies recognize distinct conformational shapes on the surfaces of intact antigens involving a variety of forces 29
Both the affinity and the amount of antibody increase with repeated immunization 30
The generation of secondary antibody responses driven by memory B cells is distinct from a primary antibody response 31
Class switching leads to the production of IgG, IgA and IgE immunoglobulins 32
Class switching is preceded by transcriptional activity at the target heavy-chain C-region genes 33
Different cytokines preferentially promote or suppress switching to certain immunoglobulin classes 34
Each immunoglobulin class has specialized functional properties and a unique tissue distribution 35
The different immunoglobulin classes are selectively distributed in the body 36
Secretory IgA is the dominant antibody class within the mucosal immune system 37
Transcytosis of IgA (and IgM) across epithelia is mediated by the poly-ig receptor 38
Secretory IgA binds to mucins within the intestinal mucus layer and neutralizes pathogens and their toxins 39
Secretory IgA has several further functions at epithelial surfaces 40
Many common diseases are caused by bacterial toxins 41
High-affinity IgG and IgA antibodies neutralize bacterial toxins 42
Virus-neutralizing high-affinity IgG and IgA antibodies inhibit the infectivity of viruses 43
Antibodies can block the adherence of bacteria to host cells Salmonella spp. adhesins Neisseria gonorrhoeae pilin IgA (mucosal surfaces) / IgG (within tissues) 44
Binding to the surface of pathogens induces the staple conformation of IgM exposing binding sites for C1q 45
The classical pathway of complement activation is initiated by IgM and IgG bound to bacterial surfaces 46
Erythrocyte CR1 contributes to the efficient clearance of immune complexes from the circulation 47
Fc receptors specific for the Fc regions of different Ig classes are differentially expressed on accessory cell subsets 48
Antigen-bound immunoglobulin binds to Fc receptors with high avidity allowing cross-linking of Fc receptor 49
Fc and complement receptors on phagocytes synergize to trigger the uptake and degradation of pathogens 50
Eosinophils attacking a schistosome larva in the presence of serum from an infected patient 51
NK cells kill antibody-coated target cells by antibody-dependent cell-mediated cytotoxicity (ADCC) 52
IgE antibody cross-linking on mast-cell surfaces leads to a rapid release of inflammatory mediators 53
The humoral immune response is crucial for clearing primary infections as well as establishing protective immunity 54
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