In the mucosal immune system, IgA-secreting plasma cells are found predominantly in the lamina propria, which lies immediately below the basement membrane of many surface epithelia. From there the IgA antibodies can be transported across the epithelium to its external surface, for example to the lumen of the gut or of the bronchi (Fig. 10.28). IgA antibody synthesized in the lamina propria is secreted as a dimeric IgA molecule associated with a single J chain. This polymeric form of IgA binds specifically to a receptor called the polymeric immunoglobulin receptor (pIgR), which is present on the basolateral surfaces of the overlying epithelial cells. When the pIgR has bound a molecule of dimeric IgA, the complex is internalized and carried in a transport vesicle through the cytoplasm of the epithelial cell to its luminal surface. This process is called transcytosis. IgM also binds to the pIgR and can be secreted into the gut by the same mechanism. Upon reaching the luminal surface of the enterocyte, the antibody is released into the mucous layer covering the gut lining by proteolytic cleavage of the extracellular domain of the pIgR. The cleaved extracellular domain of the pIgR is known as secretory component (frequently abbreviated to SC) and remains associated with the antibody. Secretory component is bound to the part of the Fc region of IgA that contains the binding site for the Fcα receptor I, which is why secretory IgA does not bind to this receptor. Secretory component serves several physiological roles. It binds to mucins in mucus, acting as ‘glue’ to bind secreted IgA to the mucous layer on the luminal surface of the gut epithelium, where the antibody binds and neutralizes gut pathogens and their toxins (see Fig. 10.28). Secretory component also protects the antibodies against cleavage by gut enzymes.
The principal sites of IgA synthesis and secretion are the gut, the respiratory epithelium, the lactating breast, and various other exocrine glands such as the salivary and tear glands. It is believed that the primary functional role of IgA antibodies is to protect epithelial surfaces from infectious agents, just as IgG antibodies protect the extracellular spaces inside tissues. By binding bacteria, virus particles, and toxins, IgA antibodies prevent the attachment of bacteria and viruses to epithelial cells and the uptake of toxins, and provide the first line of defense against a wide variety of pathogens. IgA is also thought to have an additional role in the gut, that of regulating the gut microbiota (see Chapter 12). The alveolar spaces in the lower respiratory tract lack the thicker mucosal layer characteristic of the upper respiratory tract, because efficient gas diffusion would be impeded by a mucous layer covering the alveolar epithelium. IgG can rapidly transudate into these spaces and is the major isotype responsible for protection there.