Mucosal surface of the gut tube is constantly challenged by the presence of ingested microorganisms (i.e., viruses, bacteria, parasites) and toxins, which after compromising the epithelial barrier may cause infections or diseases. An example of a specific defense mechanism is the immunoglobulinmediated response using IgA, IgM and IgE antibodies. Most of the plasma cells in the lamina propria of the intestine secrete dimeric dIgA antibodies rather than the more common IgG; other plasma cells produce pentameric IgM and IgE (see page 554). Dimeric dIgA is composed of two monomeric IgA subunits and a polypeptide J chain (see Fig. 16.28). Secreted dIgA molecules bind to the polymeric immunoglobulin receptor (pIgR) located at the basal domain of the epithelial cells (Fig. 17.24). The pIgR receptor is a transmembrane glycoprotein (75-kilodalton) synthesized by enterocytes and expressed on the basal plasma membrane. The pIgR–dIgA complex is then endocytosed and transported across the epithelium to the apical surface of the enterocyte (this type of transport refers as transcytosis). After the pIgR–dIgA complex reach the apical surface, pIgR is proteolytically cleaved and the extracellular part of the receptor that is bound to dIgA is released into the gut lumen (see Fig. 17.24). This cleaved extracellular binding domain of the receptor is known as the secretory component (SC); secreted dIgA in association with the SC is known as secretory IgA (sIgA). The release of sIgA immunoglobulins is critical for proper immunological surveillance by the mucosal immune system. In the lumen, sIgA binds to antigens, toxins, and microorganisms. Secretory IgA prevents the attachment and invasion of viruses and bacteria into the mucosa by either inhibiting their motility, causing microbial aggregation or masking pathogen adhesion sites on the epithelial surface. For example, sIgA binds to a glycoprotein on the viral envelope of HIV virus preventing its attachment, internalization, and subsequent replication in the cell.
Secretory IgA is the principal molecule of mucosal immunity. However, IgM molecules utilize similar pathway of the receptor-mediated transcytosis to reach the mucosal surface. Some of the IgE binds to the plasma membranes of mast cells in the lamina propria (see page 182), selectively sensitizing them to specific antigens derived from the lumen.
A distinguishing characteristic of the duodenum is the presence of submucosal glands.
The submucosa consists of a dense connective tissue and localized sites that contain aggregates of adipose cells. A conspicuous feature in the duodenum is the presence of submucosal glands, also called Brunner’s glands.
The branched, tubular submucosal glands of the duodenum have secretory cells with characteristics of both zymogensecreting and mucus-secreting cells (Fig. 17.25).
The secretion of these glands has a pH of 8.1 to 9.3 and contains neutral and alkaline glycoproteins and bicarbonate ions. This highly alkaline secretion probably serves to protect the proximal small intestine by neutralizing the acid-containing chyme delivered to it. It also brings the intestinal contents close to the optimal pH for the pancreatic enzymes that are also delivered to the duodenum.