Figure 1. Secretory IgA (sIgA). Dimeric IgA (IgA2) is the predominant form present along mucosal surfaces and is formed by two IgA monomer subunits attached together by the J chain. sIgA is noncovalently bound to polymeric immunoglobulin receptor (pIgR) derived secretory component to protect it from digestion by luminal proteases.

Figure 2. Polymeric immunoglobulin receptor (pIgR) transport. pIgR binds to IgA (or IgM) on the basolateral surface of the epithelial cell and this complex then undergoes transcytosis. pIgR is then cleaved at the apical surface, forming secretory component (SC) bound IgA that enters the lumen. The remaining portion of the pIgR is nonfunctional and undergoes intracellular degradation. SC protects sIgA and sIgM from luminal degradation.

Figure 3. gut-associated lymphoid tissue (GALT). Peyer's patches (PP) and mesenteric lymph nodes (MLNs) are the major inductive sites present in GALT. The PP contains three distinct divisions: the subepithelial dome (SED) populated by lymphocytes and DC, distinct B cell-containing follicles organized into germinal centres, and parafollicular zones containing T cells and high endothelial venules (HEV). Overlying the dome is the FAE-containing M cells whose numerous microfolds and large invaginated subdomains increase the surface area of antigen sampling, (IEC, intestinal epithelial cell).

Figure 4. Antigen presentation by IECs. Antigen is sampled in the lumen and subsequently transported to the basolateral surface where it binds to the restriction element CD1d. Together with CEA, CD1d presents the antigen to CD8+ T cells to induce the activation and proliferation of a subset of regulatory T cells (T_RE cells). These cells are phenotypically characterized by the expression of CD101 and CD103 and lack of CD28. IECs do not express the conventional co-stimulatory molecules CD80 or CD86, and instead utilize B7 h and B7H1.

Figure 5. T_H1 and T_H2 cytokine regulation. (a) In T_H1 cells, IL-12 activates STAT4, which will induce production of IFN and the IL-12 receptor. Upon binding of IL-12 to this receptor, STAT4 is activated and IFN produced. Overexpression of T-bet could potentially contribute to T_H1-mediated mucosal diseases such as Crohn disease. (b) In T_H2 cells, IL-4 induces cytokine production via activation of STAT6 followed by activation of the master transcription factor GATA-3. Overexpression of GATA-3 predisposes to T_H2-mediated mucosal diseases such as asthma.