The immunology of gluten hypersensitivity and celiac disease has been pursued with significant interest in the past 20 years. For the prevention of systemic diseases, most pathogens that gain entry into our bodies must be met with an effective immune response, yet in the gastrointestinal tract it is equally important that commensal bacteria and a diverse collection of dietary proteins and peptides be recognized without eliciting an active immune response or constant activation of the inflammatory pathway. This phenomenon of hyporesponsiveness to food antigens is known as oral tolerance.

This oral tolerance to dietary antigens is maintained by three different mechanisms: anergy, cell deletion and immune suppression. However, in the presence of mechanical/ chemical stressors and infections, this tolerance may break down, and gut associated lymphoid tissues (GALT) will react to different luminal antigens. The reaction of GALT to these antigens may lead to the production of pro-inflammatory cytokines, opening of tight junctions, entry of undigested antigens into the circulation, and the subsequent production of IgA, IgG, IgM and IgE antibodies in blood and secretory components.

Like any other food hypersensitivity reaction, gluten sensitivity can be divided into immediate and delayed hypersensitivities. In this review an attempt is made first to differentiate immediate hypersensitivity to gliadin, mediated by IgE, from delayed hypersensitivity, which is mediated by IgA and IgG. Furthermore, we attempt to differentiate between gluten hypersensitivity with enteropathy (celiac disease) and gluten hypersensitivity without enteropathy.