Immunology Notes

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Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

Immunology NotesNov 112Stimulating a B cell BCR signalling complexlike T cell antigen specific signal TLRspresent antigen to T cells APC functioninteractions with T cells CD40 signal is important for activating B cells Stimulating a B cell The first signal required for B cell activation is delivered through the antigen receptor the antigen is displayed as a peptide on MHC class II A second signal is required for B cell activation In thymusdependent T cell dependent antigens the signal is delivered by a helper T cell that recognizes the peptide There is an interaction between CD40L on the T cell and CD40 on the B cell In thymusindependent antigens a second signal can be delivered along with the antigen itself through TLRs that recognize LPS bacterial polysaccharides can induce antibody production in the absence of helper T cells TI1 antigens Are antigens coupled to a TLR ligand such as LPS or bacterial DNA At high concentrations of TLR ligand TI1 antigen polyclonal activation occurs which is when B cells are induced to secrete antibody in the absence of specific antigen binding to surface Ig There is a nonspecific antibody response IgM is produced All B cells respond even though only one of them is actually bound to antigen the rest are bound to TLR ligand BCR stimulation equals TLR upregulation stimulation of BCR by antigen will make it express more TLR At low concentrations of TLR ligand there is antigenspecific activation via TLRs Only B cells specific for the TI1 antigen bind enough it of it to focus its B cell activating properties onto the B cell There is an antigenspecific antibody response only those B cells that bind the antigen will undergo proliferation and differentiation and produce antibodies TI1 antigens include LPS proteincarbohydrateLPS experimental antigen They can activate immature and mature B cells TI2 antigensResults from extensive BCR crosslinking They are repetitive antigens with multiple epitopes such as bacteria capsule polysaccharides and experimental antigens They only activate mature B cells They produce mostly IgM but also IgG and IgG3 in mice Cytokine help from surrounding cells DCs provide costimulatory signals for activation survival and differentiation The cytokine BAFF helps induce class switching produce IgG antibodies Stimulating a B cell Thymusindependent activation doesnt have to occur in secondary lymphoid tissue B1 cells and MZ cells are often activated via TI2 antigen mechanisms Thymusdependent activation typically occurs in secondary lymphoid tissue It requires contact with T cells specific for a linked antigen When circulating nave B cells migrate into lymphoid tissues they enter the primary lymphoid follicles attracted by the chemokine CXCL13 Within the follicle FDCs secrete CXCL13 and nave B cells express CXCR5 the receptor for this chemokine FDCs are not bone marrowderived and do not display antigen Within the B cell follicle there is CD35 and IgDa Antigen enters into the supcapsular sinus and is taken up by specialized macrophages that reside there They transport the antigen into the B cell follicle B cells look for antigen Once a nave B cell in the follicle encounters its specific antigen this induces expression of the chemokine receptor CCR7 EB12 and expression of CXCR5 is retained The B cell needs T cell help so it moves toward the T cell zone where chemokine ligands for CCR7 such as CCL21 are highly expressed by stromal cells and DCs T cell is expressing CCR7 When a nave
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