3.04 - The Gastrointestinal Immune System

Abstract

The gastrointestinal immune system is in constant contact with gut luminal antigens and commensal bacteria. It has two major seemingly contradictory missions: (1) protect the intestine from pathogens but (2) induce immune tolerance to commensal bacteria and food antigens. The barrier function provided by epithelial cells and their products such as mucus secretion and antibacterial peptides serves as the first line of defense to prevent infection. The intestinal tract has highly organized lymphoid tissues such as Peyer’s patches and the mesenteric lymph node to surveillance pathogens in the intestine. The intestinal immune system develops immune tolerance to harmless antigens by producing suppressive cytokines and regulatory metabolites, which induce regulatory cells to suppress immune responses. The gut immune system recognizes pathogens with specialized 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 innate immune cells, macrophages, eosinophils, mast cells, T cells, and B cells. Intestinal T and B cells express gut-homing receptors to migrate into the intestine. These lymphocytes fight pathogens through antigen-specific immune responses. Uncontrolled immune responses to harmless gut antigens can cause inflammatory bowel disease and food allergy. Vitamin A metabolites and short-chain fatty acids provide gut tissue-specific signals important for regulation of both immunity and tolerance.