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Mucosal Immunity

WARNING! extreme science ahead

 

Mucosal Immunity

-Nature.com

Gastrointestinal Tract

The largest immunologic organ in the body is the gastrointestinal (GI) tract.  A tremendous amount and variety of food proteins come in contact with our immune cells in the GI tract. Rather than mount an immune response against these proteins, the normal reaction of the immune system is not to react to them (tolerance). A failure to develop oral tolerance or a loss of oral tolerance is hypothesized to be the primary problem in food allergy.

When a food is ingested in a nonallergic person, the food proteins are broken down and digested by gastric acids and digestive enzymes. This process decreases the immunogenicity (the ability to stimulate the immune system) of the proteins. The normal process of digestion may be disrupted and lead to a breakdown in oral tolerance induction.

 

Tolerance

The development of tolerance relies on several important factors

  • Form and dose of the antigen

  • Genetics of the host

  • Normal intestinal flora of the host

  • Age of the host

Gastric acidity in addition to GI proteases are important in normal digestion, and a breakdown in this process leads to a change in the form of the antigen  (antigens in the soluble form are more tolerogenic than antigens in particulate form)

The solubility of food proteins may be affected by how the foods are prepared. For example, in peanuts, roasting decreases the solubility and enhances binding of peanut-specific IgE. The dose of food antigen exposure influences how oral tolerance develops.

Immunesystem regulation

High doses of antigen favor an anergy-driven pathway to tolerance, whereas low doses of antigen promote a suppressive pathway to tolerance via regulatory T cells (TRegs).  TRegs are a subset of T lymphocytes that possess the ability to decrease the proliferative activity of other lymphocytes.

  •  High-dose tolerance

    • T cell receptor ligation in the absence of costimulatory signals (interleukin (IL)-2, interactions between CD28 on T cells with either CD80 or CD86 on antigen-presenting cells.)

  • Low-dose tolerance

    • By the action of TRegs and CD81 T cells (production of cytokines such as IL-10 and transforming growth factor TGFβ.)

 

Genetics

The genetics of the host influence the development of tolerance, but the role of genetic factors has not been as clearly understood.

Limited studies examining associations between specific human leukocyte antigens (HLA) with food allergies has shown variable results. There is some evidence that, in peanut allergies, specific HLA class II genotypes may be found in a higher frequency of peanut allergic patients compared with controls.  This area continues to be investigated.

Age

A study investigating the roles of age and timing in the development of allergy is currently underway in the United Kingdom. This study, the Learning Early About Peanut Allergy (LEAP) study, involves children between 4 and 10 months of age who are randomized to either eat peanuts regularly 3 times a week or to avoid peanuts until the age of 3 years. Study completion is anticipated by 2013 (http://www.leapstudy.co.uk).

 

Oral desensitization for food hypersensitivity. Immunol Allergy Clin North Am. 2011 May;31(2):367-76.

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