The gut as communicator between environment and host: immunological consequences

Eur J Pharmacol. 2011 Sep;668 Suppl 1:S16-32. doi: 10.1016/j.ejphar.2011.07.006. Epub 2011 Jul 28.

Abstract

During human evolution, the mucosal immune system developed two anti-inflammatory mechanisms: immune exclusion by secretory antibodies (SIgA and SIgM) to control epithelial colonization of microorganisms and inhibit penetration of harmful substances; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens such as food proteins. The latter function is referred to as oral tolerance when induced via the gut. Similar mechanisms also control immunity to commensal bacteria. The development of immune homeostasis depends on "windows of opportunity" where adaptive and innate immunities are coordinated by antigen-presenting cells; their function is not only influenced by microbial products but also by dietary constituents, including vitamin A and lipids like polyunsaturated omega-3 fatty acids. These factors can in several ways exert beneficial effects on the immunophenotype of the infant. Also breast milk provides immune-modulating factors and SIgA antibodies - reinforcing the gut barrier. Mucosal immunity is most abundantly expressed in the gut, and the intestinal mucosa of an adult contains at least 80% of the body's activated B cells - terminally differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric IgA which is exported by secretory epithelia expressing the polymeric Ig receptor (pIgR), also called membrane secretory component (SC). Immune exclusion is therefore performed mainly by SIgA. Notably, pIgR knockout mice which lack SIgs show increased uptake of food and microbial antigens and they have a hyper-reactive immune system with disposition for anaphylaxis; but this untoward development is counteracted by cognate oral tolerance induction as a homeostatic back-up mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Environment*
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Homeostasis / immunology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Hypersensitivity / immunology
  • Hypersensitivity / microbiology