Humoral Immunity - Lecture notes Immunology PDF

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Physiological Systems and Immunology...

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Humoral Immunity Humoral Immunity, is mediated by antibody Ab is secreted from activated B cells Naïve B cells when stimulated by cognate antigen: - become Ab secreting plasma cells - produce IgM Memory B cells respond more quickly & strongly to Ag class switch to produce high affinity antibodies especially IgA + IgG Antibody responses

1o response Innate immunity - limits response Microbe multiplies causing disease symptoms 2o response is so fast and that are no disease symptoms IgA - neutralisation of entry IgG - prevents spread IgG + complement + phagocytes opsono phagocytosis

Generation of B cell memory requires T cell help (in lymphnodes)

This is called T cell dependent activation of naïve B cells:• protein antigen specific • needs presentation of Ag • class switch is helped by Th2 cell cytokines

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BCR binds a specific antigenic epitope B cell processes & presents antigen to T cell – which sees a different epitope IL-4, IL-5, IL-6 + others

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(B cell) CD40 interacts with CD40L (Th2)- essential Th2 cytokines induce proliferation & differentiation of the B cell B cells lacking CD40L result in X-linked hyper IgM syndrome TH1 cytokines IFNg stims just IgG (c fixing) Mucosal epithelium cytokine TGFB- stims just IgA switch

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B cells can also be activated T cell- independently (TI), like during maturation in the bone marrow . TI-1 mitogens (cause B cell proliferation) B cell can be activated independently of the BCR eg bacterial LPS binding to B cell TLRs secrete IgM, no memory TI-2 repeating antigens multiple BCR may be cross linked eg bacterial capsule polysaccharide

Activation of B cells Toll like receptor 4 binds to LPS

T dependent class switch to anything but IgM. Activation of B cells- summary B cells are activated in lymph nodes Activation can be T cell independent (TI) TI-1 TI-2

bacterial mitogens bacterial capsule polysaccharides

Activation can be Th cell dependent – clonal expansion of T + B (increased by activated complement) Activation results in B cell clonal / polyclonal proliferation + plasma cell formation + Ab B cells are also antigen presenting cells 1o response here presentation is mostly by dendritic cells (DC) Ag is in the periphery - skin, mucosa DC migrate with Ag to lymph nodes They process and present Ag to naïve T cells 2o response presentation is mostly by macrophages and B cells collect, process and present Ag to memory T cells

In lymph nodes and at site of infection Memory B cells Long term! • Faroe islanders - immune to measles 65 years after contact with virus • US Yellow fever trial vaccine - Ab in blood 70 years later Produced in Lymph nodes / MALT Produced in germinal centres (GC) in B cell follicle

T dependent B cells Make memory cells + plasma cells Need Th(CD40-CD40L)+(cytokines IL4,5) Long lived memory, IgA/ G/ D/ E Respond to protein Ag T independent B cells Make IgM only + No memory Respond to LPS via TLR; or P/S via BCR B cells as APC Mostly present to memory T cells B cells are antigen presenting cells B cells can only take up antigen specific to its receptor In contrast macrophages and DC can uptake any antigen B cells present a different antigenic epitope to T cells Mucosal surface responses 50% of all lymphocytes are in the MALT 2/3 of all B cells secrete IgA Mucosa Associated Lymphoid Tissue MALT= BALT+ GALT+ NALT Memory plasma cell migrates to below epithelium...