The human intestinal immune system: Basic cellular and humoral mechanisms

Summary Adaptive immune protection of mucous membranes is provided mainly by secretory IgA (SIgA) antibodies. This first-line defence is accomplished through an ingenious cooperation between the mucosal B-cell system and the epithelial glycoprotein called secretory component (SC). This is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA), which is the major humoral mediator substance of the whole immune system. Transmembrane SC belongs to the Ig supergene family and functions as a general pIg receptor, also translocating pentameric IgM externally to form secretory IgM. The B-cells responsible for local pIg production are initially stimulated in lymphoepithelial structures, particularly the Peyerʹs patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory site. There is currently great interest in exploiting this integrated or ‘common’ mucosal immune system for oral vaccination against pathogenic infectious agents and also to induce therapeutic peripheral tolerance to ameliorate T-cell-mediated autoimmune diseases. Much remains to be learnt about antigen uptake and processing necessary to elicit stimulatory or suppressive mucosal immune responses, and how normal homeostasis is maintained in the intestinal mucosa. Considerable information has accumulated about various types of immune deviation that may lead to local or extraintestinal hypersensitivity reactions against luminal antigen, but the crucial mechanisms remain obscure