Immune tolerance

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Immune or immunological tolerance is the process by which the immune system does not attack an antigen. It occurs in three forms: central tolerance, peripheral tolerance and acquired tolerance.

Central tolerance

Central tolerance is immunological tolerance developed during T and B cell differentiation.

Peripheral tolerance

Peripheral tolerance is immunological tolerance developed after T and B cells mature and enter the periphery.

Acquired tolerance

Acquired or induced tolerance refers to the immune system's adaption to external antigens characterized by a specific non-reactivity of the lymphoid tissues to a given antigen that in other circumstances would likely induce cell-mediated or humoral immunity. One of the most important natural kinds of acquired tolerance occurs during pregnancy, where the fetus and the placenta must be tolerated by the maternal immune system. One model for the induction of tolerance during the very early stages of pregnancy is the eutherian fetoembryonic defense system (eu-FEDS) hypothesis. [1] However, another model suggests that the induction of tolerance primarily requires the participation of regulatory T cells[2].

In adults, tolerance may be induced by repeated administration of very large doses of antigen, or of small doses that are below the threshold required for stimulation of an immune response. Tolerance is most readily induced by soluble antigens administered either intravenously or sublingually. Immunosuppression also facilitates the induction of tolerance.

In clinical practice, acquired immunity is important in organ transplantation, when the body must be forced to accept an organ from another individual. The failure of the body to accept an organ is known as transplant rejection. To prevent rejection, a variety of medicines are used to produce induced tolerance.

One of the most important forms of acquired tolerance is oral tolerance. [3] Oral tolerance, the specific suppression of cellular and/or humoral immune reactivity to an antigen by prior administration of the antigen by the oral route, probably evolved to prevent hypersensitivity reactions to food proteins and bacterial antigens present in the mucosal flora.[4] It is of immense immunological importance, since it is a continuous natural immunologic event driven by exogenous antigen. Due to their privileged access to the internal milieu, antigens that continuously contact the mucosa represent a frontier between foreign and self components. Oral tolerance evolved to treat external agents that gain access to the body via a natural route as internal components without danger signals, which then become part of self. Failure of oral tolerance is attributed to the development and pathogenesis of several immunologically based diseases, including Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis).


  1. Clark, Clark G.F., Dell A., Morris H.R., Patankar M.S., and Easton R.L. (2001) The species recognition system: a new corollary to the human fetoembryonic defense system hypothesis. Cells Tissues Organs 168, 113-21 PMID 11114593
  2. Trowsdale J, and Betz AG. 2006. Mother's little helpers: mechanisms of maternal-fetal tolerance. Nature Reviews Immunology 7:241-6 PMID 16482172
  3. Lloyd Mayer, Kirk Sperber, Lisa Chan, Joseph Child, Lisa Toy (2001) Oral tolerance to protein antigens Allergy 56 (s67), 12–15. doi:10.1111/j.1398-9995.2001.00904.x
  4. Howard L. Wiener. "Oral tolerance, an active immunologic process mediated by multiple mechanisms." (October 2000) Journal of Clinical Investigation. Volume 106, Number 8, pages 935-937

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de:Selbsttoleranz it:Tolleranza immunologica