消化系统免疫学课件.ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * mice (left model), DCs lodged in the subepithelial dome of Peyer’s patches capture bacteria or antigen internalized by M cells or by epithelial cells (ECs) via receptor-mediated endocytosis. These DCs migrate to the interfollicular region (IFR) of Peyer’s patches, where they present antigen to CD4+ T cells. Antigenactivated CD4+ T cells elicit IgA class switching by stimulating IgM+IgD+ B cells through CD40L and TGF. A subset of Peyer’s patch DCs, TNF-a+iNOS+ DCs, enhance IgA class switching by upregulating the expression of the TGF-b receptor on B cells through nitric oxide (NO). In the presence of retinoic acid (RA), IgA+ B cells upregulate the expression of CCR9 and a4b7 and thereafter migrate to the lamina propria, where they differentiate into plasma cells that release dimeric IgA antibodies. This T cell-dependent pathway yields high-affinity, monoreactive IgA antibodies that preferentially target pathogens and toxins. IgA class switching can also take place in the lamina propria via a T independent mechanism that involves activation of B-1 cells and possibly other IgM+IgD+ B cell subsets by DCs, including TNF-a+iNOS+ DCs. These DCs release innate IgA class-switch-inducing factors, such as BAFF, APRIL, TGF-b, and NO, as well as IgA secretion- inducing factors, such as IL-6 and RA, after sensing bacteria through TLRs. NO amplifies IgA class switching by enhancing BAFF and APRIL production by DCs. This T cell-independent pathway preferentially yields low-affinity, polyreactive IgA antibodies to commensal bacteria. In humans (right model), CD4+ T cells elicit IgA1 class switching by activating Peyer’s patch IgM+IgD+ B cells through CD40L and TGF-b. The resulting IgA1+ B cells migrate to the lamina propria through a mechanism presumably similar to that utilized by mouse IgA+ B cells. In the lamina propria, IgA1+ B cells sequentially switch to IgA2 in response to APRIL and IL-10 rele