In some animals there is a second route of IgA secretion into the intestine— the hepatobiliary route. Dimeric IgA that has not bound pIgR is taken up into venules in the lamina propria, which drain intestinal blood to the liver via the portal vein. In the liver these small veins (sinusoids) are lined by an endothelium that allows the antibodies access to underlying hepatocytes, which have pIgR on their surface. IgA is taken up into the hepatocytes and transported by transcytosis into an adjacent bile duct. In this way, secretory IgA can be delivered directly into the upper small intestine via the common bile duct. This hepatobiliary route allows dimeric IgA to eliminate antigens that have invaded the lamina propria and have been bound there by IgA. Although highly efficient in rats and other rodents, this route does not seem to be of great significance in humans and other primates, in whom hepatocytes do not express pIgR.
IgA secreted into the gut lumen binds to the layer of mucus coating the epithelial surface via carbohydrate determinants in secretory component. There it is involved in preventing invasion by pathogenic organisms and, just as important, it also has a crucial role in maintaining the homeostatic balance
Fig. 12.11 Transcytosis of IgA antibody across epithelia is mediated by the polymeric Ig receptor (pIgR), a specialized transport protein. Most IgA antibody is synthesized in plasma cells lying just beneath epithelial basement membranes of the gut, the respiratory epithelia, the tear and salivary glands, and the lactating mammary gland. The IgA dimer linked by a J chain diffuses across the basement membrane and is bound by the pIgR on the basolateral surface of the epithelial cell. The bound complex undergoes transcytosis, by which it is transported in a vesicle across the cell to the apical surface. There the pIgR is cleaved, leaving the extracellular IgA‑binding component bound to the IgA molecule as the so‑called secretory component. Although not shown, carbohydrate on the secretory component binds to mucins in mucus and holds the IgA at the epithelial surface. The residual piece of the pIgR is nonfunctional and is degraded. IgA is transported across epithelia in this way into the lumina of several organs that are in contact with the external environment.
Fig. 12.12 Mucosal IgA has several functions in epithelial surfaces. First panel: IgA adsorbs on the layer of mucus covering the epithelium, where it can neutralize pathogens and their toxins, preventing their access to tissues and inhibiting their functions. Second panel: antigen internalized by the epithelial cell can meet and be neutralized by IgA in endosomes. Third panel: toxins or pathogens that have reached the lamina propria encounter pathogen‑specific IgA there, and the resulting complexes are reexported into the lumen across the epithelial cell as the dimeric IgA is secreted. Fourth panel: antigen bound to secretory IgA in the lumen can bind via carbohydrate residues on the Fc portion of IgA to Dectin‑1 on M cells in Peyer’s patches and be transported to underlying dendritic cells. Binding of the IgA‑containing complex to DC‑SIGN on the dendritic cells induces them to produce anti‑inflammatory IL‑10.
between the host and the commensal microbiota. It does this in a number of ways (Fig. 12.12). First, it inhibits microbial adherence to the epithelium, its ability to bind bacteria being assisted by the unusually wide and flexible angle between the Fab pieces of the IgA molecule, particularly the IgA1 isotype (see Section 5-12), allowing very efficient bivalent binding to large antigens such as bacteria. Secretory IgA can also neutralize microbial toxins or enzymes.