Immunology 17 - Immunology 17-Humoral Immunity Stimulating...

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Immunology 17-Humoral Immunity Stimulating a B Cell 1. BCR signalling; 2. TLRs; 3. APC function—interaction with T ells B cells only take up Ag through BCR; interactions between CD40 and CD40L activates B cells Phosphorylation of ITAms on BCR tails by Src family kinases Thymus (T-cell) dependent antigens vs thymus independent antigens Thymus Independent -1 Antigens Antigens coupled to a TLR ligand (LPS, bacterial DNA) Requires high concentrations of TLR ligand→ polyclonal activation= non specific Ab response; expansion; Ab production (IgM) BCR stimulation= TLR upregulation (antigen specific activation via TLRs causes upregulation of TLRs); 1000x lower concentrations of ligand; more sensitive at decreased concentration TI-1 antigens: LPS, protein/carbohydrate + LPS, experimental antigens (via linking to LPS) Thymus independent -2 Antigens Results from extensive BCR crosslinking Repetitive antigens: Multiple epitopes: capsule polysaccharides, experimental Ags Mostly IgM; also IgG; cytokine help from surrounding cells (DCs) TI-2 antigens alone can signal B cells to produce IgM antibody Stimulating a B cell: Thymus independent activation: doesn’t have to occur in secondary lymphoid tissue; B-1 cells and MZ B cells are often activated via these mechanisms Thymus-dependent activation: typically occurs in secondary lymphoid tissues; requires contact with T cells specific for a “linked” antigen In the lymph node: B cells reside in the B cell follicles due to expression of CXCR5 which is attracted to CXCL13; follicular DCs also reside in the B cell follicles (are not APCs or bone marrow derived; not related to normal DC) Ag comes through afferent lymphatic vessel into subcapsular sinus; really small Ags can enter directly into follicle; bigger Ags must be transported y macrophages into the follicle Activation correlates with change in location; activated B cells upregulate CCR7 (to migrate to T cell zone) and EB12 (help in migration to periphery) T cells become activated in T cell zone and upregulate CXCR5 which induces migration towards the B cell follicle; therefore both cells express both signals and come together; meet between area between 2 follicular zones= interfollicular zone B cell as an APC Very potent APC to CD4 T cells; but only for specific antigens; antigen uptake occurs primarily through binding to the BCR B cells do not require APC to recognize Ag but T cells do “linked recognition” and T cell help: present peptides derived from specific antigen, or protein physically associated with the specific antigen; B cell takes up entire virus and presents its peptides; doesn’t necessarily recognize the same protein as T cell but is some how linked B cell can bind virus through viral coat protein; the virus particle is internalized and degraded; peptides from internal proteins of the virus are presented to the T cell, which activates the B cell; activated B cell produces Ab against viral protein
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Immunology 17 - Immunology 17-Humoral Immunity Stimulating...

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