The Gastrointestinal Immune System

The gastrointestinal immune system is in constant contact with gut luminal antigens and commensals because it is separated from the gut antigens by only a single layer of epithelial cells and actively samples them. It has two major seemingly contradictory missions: (1) protect the intestine from pathogens; but (2) induce immune tolerance to commensals and food antigens. The barrier function provided by epithelial cells and their products such as mucus and antibacterial molecules serves as the first line of defense to prevent infection. The intestinal tract has highly organized lymphoid patches and the draining mesenteric lymph node to screen antigens in the tissue system. The intestinal immune system actively induces immune tolerance to harmless antigens by inducing immune response-dampening regulatory cells. It has the ability to distinguish harmless antigens from potential pathogens employing various receptors for pathogen-associated molecular patterns. Upon detection of pathogens, the intestinal immune system chooses to mount effective immune responses by activating immune effector cells such as macrophages, T cells, B cells, eosinophils, and mast cells. Intestinal T and B cells have a gut-specific homing behavior that allows them to effectively surveil the tissue system. Uncontrolled hyperresponses to harmless gut antigens can cause inflammatory bowel disease and food allergy. Vitamin A metabolites provide a gut-specific signal important for the regulation of both immunity and tolerance.