The intestinal immune system and its relation to disease

The essential protective structure against the heavy enteric antigenic burden, the gut mucosa, prevents penetration of noxious agents, but allows a minimal exchange of large molecules and particles between the gut lumen and the 'milieu intérieur' of the body. M cells in the follicle-associated epithelium of the gut, ideal gateways for the presentation of enteric antigens to the cells of the gut-associated lymphoid tissue (GALT), are also weak links in the mucosal barrier, and may provide access for various microorganisms. The afferent limb of the GALT consists of distinct aggregates of lymphoid cells located in Peyer's patches, the vermiform appendix and the solitary lymphatic follicles, and of the mesenteric lymph nodes. The efferent limb subsumes the diffusely scattered mucosal leukocytes, mainly lymphocytes and plasma cells. Intraepithelial and mucosal T lymphocytes are instrumental in launching local immune responses, producing lymphokines, and in the specific lysis of virally infected cells. Antigenic stimulation of the GALT results in local secretion of antibodies, or in suppression of systemic immunologic responses to ingested antigens ('oral tolerance'). Poorly controlled mucosal immune responses result in organ-specific diseases. Extranodal lymphomas that mimic structures of the GALT may arise on a background of inflammatory or immunologic (autoimmune) disorders.