Development of Oral Tolerance

"Oral (food) tolerance" usually describes a clinical situation that is not necessarily synonymous with the immunological definition of "tolerance," that is, as observed during development, transplantation or neonatal tolerance. In the context of this chapter, "oral tolerance" is defined as an antigen-specific immunological hyporesponsiveness after prior enteral administration. Oral exposure to foods or other ingested antigens has two major effects on the immune system. These reactions can be generalized (i.e., simplified) as leading to (a) induction of systemic immunological hyporesponsiveness (tolerance) or (b) sensitization and priming. Although the suppressive effects of oral antigen ingestion have been described in anecdotal form for over 150 years, the underlying immunoregulatory mechanisms are still poorly understood and remain controversial at times. The development of oral tolerance is thought to be the basic immunologic mechanism that prevents adverse effects (hypersensitivity/food allergy) after intestinal antigen exposure. There is little doubt that systemic suppression of specific immune responses exists in humans, but for ethical reasons most reports in humans are circumstantial (1,2). A great deal of basic work has been performed on laboratory rodents for only a limited range of food and other T-cell-dependent antigens (e.g., milk and egg proteins, sheep erythrocytes, and organ-specific antigens) (3-5). A breakdown or modulation of these important homeostatic mechanisms is likely to be one of the reasons for the development of sensitizations after food intake. Suppression of systemic immunity after a feed usually does not include B cell responses. Serum antibody production of infants (or adults) against food proteins is a universal phenomenon and is usually not related to an intolerance phenomenon to the antigen in question. Most low-level food antibodies of clinically tolerant individuals are of the immunoglobulin G (IgG) class. Increased serum or mucosal antibodies to food proteins or tissue constituents of the IgA or IgE class are more likely to be an indicator of a possible underlying pathological process (e.g. celiac disease, acute onset cow's milk allergy) (6,7).