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The Intestinal Immune System in Health

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Crohn's Disease and Ulcerative Colitis

Abstract

In order to preserve the intestinal barrier and maintain homeostasis, the mucosal immune system possesses two layers of anti-inflammatory defense: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonization of microorganisms and dampen penetration of potentially harmful antigens; and (2) suppressive mechanisms to avoid local and peripheral hypersensitivity to innocuous antigens, particularly food proteins and components of the commensal microbiota. When induced via the gut, the latter phenomenon is called “oral tolerance,” which largely depends on the development of regulatory T (Treg) cells in mesenteric lymph nodes to which mucosal dendritic cells (DCs) carry exogenous antigens and become conditioned for induction of Treg cells. Mucosally induced tolerance appears to be a rather robust adaptive immune function in view of the fact that large amounts of food proteins pass through the gut, while overt and persistent food allergy is not so common. Moreover, most individuals live in harmony with an intestinal population of commensal bacteria which is some ten times the number of cells of the body. This homeostatic mutualism is regulated by specialized DCs that are “decision makers” of the immune system when they perform their antigen-presenting function, thus linking innate and adaptive immunity by sensing the exogenous impact in terms of conserved microbial molecular patterns. A balanced indigenous microbiota is required to drive the normal development of both mucosa-associated lymphoid tissue, the epithelial barrier with its secretory IgA (and IgM) system, and mucosally induced tolerance mechanisms – including the generation of Treg cells. Notably, polymeric Ig receptor (pIgR/SC) knockout mice that lack secretory IgA and IgM antibodies show reduced epithelial barrier function and increased uptake of antigens from food and commensal bacteria. They therefore have a hyperreactive immune system and show predisposition for systemic anaphylaxis after antigen sensitization; but this untoward development is counteracted by enhanced intestinal induction of cognate oral tolerance as a homeostatic back-up mechanism.

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Acknowledgments

The author is grateful to Hege Eliassen for excellent secretarial assistance. Studies at LIIPAT were supported by the Research Council of Norway, the University of Oslo, and Oslo University Hospital.

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Authors and Affiliations

  1. Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation (CIR), University of Oslo, Oslo, Norway

    Per Brandtzaeg MS, DSS, PhD

  2. Department of Pathology, Oslo University Hospital, Rikshospitalet, Nydalen, 4950, N-0424, Oslo, Norway

    Per Brandtzaeg MS, DSS, PhD

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  1. Per Brandtzaeg MS, DSS, PhD
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Correspondence to Per Brandtzaeg MS, DSS, PhD .

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  1. Medical School of the Humboldt Universit, Department of Medicine, Charité Medical Center, Virchow Hospita, Berlin, 13344, Germany

    Daniel C. Baumgart

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Brandtzaeg, P. (2012). The Intestinal Immune System in Health. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0998-4_3

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