2. Functional anatomy of induction of immune responses by intestinal antigens. Abundant protein antigens and live commensal bacteria are present in the intestine. Antigenic peptides can pass into the bloodstream through one of the tributaries of the hepatic portal vein or are taken up by DCs in the subepithelial region of the Peyer's patches and carried to the MLNs via the afferent lymphatics. Although it is possible for circulating peptides to tolerize T cells in the liver or peripheral lymph nodes, presentation in the MLNs is the dominant tolerogenic pathway. Commensal bacteria are also sampled by intestinal DCs and induce IgA responses in the Peyer's patches; although very small numbers of commensals can be carried to MLN by DC, systemic tolerance to these organisms is not induced. Because the commensal laden DCs do not penetrate further than the MLN, the systemic immune system is protected from unwanted priming reactions from live bacteria. Immune ignorance by the adaptive immune system outside the GALT of antigens, taken-up in the intestinal mucosa Macpherson & Smith J Exp Med. 203(3): 497–50; 2006
27. IgA dimerisation and secretion IgA is the major isotype of antibody secreted at mucosal surfaces Exists in serum as a monomer, but more usually as a J chain-linked dimer, that is formed in a similar manner to IgM pentamers. IgA exists in two subclasses IgA1 is mostly found in serum and made by bone marrow B cells IgA2 is found in higher concentration in mucosal secretions, colostrum and milk and is made by (??? ) J C C S S S S C C S S S S C C s s
28. Secretory IgA and transcytosis ‘ Stalk’ of the pIgR is degraded to release IgA containing part of the pIgR - the secretory component Epithelial cell J C C S S S S C C S S S S C C s s B J C C S S S S C C S S S S C C s s J C C S S S S C C S S S S C C s s J C C S S S S C C S S S S C C s s pIgR & IgA are internalised J C C S S S S C C S S S S C C s s IgA and pIgR are transported to the apical surface in vesicles B cells located in the submucosa produce dimeric IgA Polymeric Ig receptors are expressed on the basolateral surface of epithelial cells to capture IgA produced in the mucosa