The largest lymphoid organ in the body is the gut and the gut-associated lymphoid tissue. The mucosal immune system faces many challenges in protecting the body from microbial invasion. Its chief function is to maintain a diverse population of mature lymphocytes capable of responding to foreign antigens. This task is accomplished with a variety of unique features that distinguish the mucosal from the systemic immune system. In addition, the mucosal immune system plays a role in inflammatory bowel disease, Whipple disease, autoimmune gastritis, Helicobacterpylori infection, immunoproliferative small intestinal disease, hepatitis A, B, C, D, E, F, and G, autoimmune hepatitis, primary biliary cirrhosis, progressive sclerosing cholangitis, and vanishing bile duct syndrome.