title: Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora.
abstract: Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.
authors.affiliation: Division of Immunology and Gnotobiology, Academy of Sciences of the Czech Republic, Prague.
authors.forename: H
authors.initials: H
authors.lastname: Tlaskalová-Hogenová
authors.forename: R
authors.initials: R
authors.lastname: Stĕpánková
authors.forename: L
authors.initials: L
authors.lastname: Tucková
authors.forename: M A
authors.initials: MA
authors.lastname: Farré
authors.forename: D P
authors.initials: DP
authors.lastname: Funda
authors.forename: E F
authors.initials: EF
authors.lastname: Verdú
authors.forename: J
authors.initials: J
authors.lastname: Sinkora
authors.forename: T
authors.initials: T
authors.lastname: Hudcovic
authors.forename: Z
authors.initials: Z
authors.lastname: Reháková
authors.forename: B
authors.initials: B
authors.lastname: Cukrowska
authors.forename: H
authors.initials: H
authors.lastname: Kozáková
authors.forename: L
authors.initials: L
authors.lastname: Prokesová
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007239:Infections / Q000276:immunology*; D007249:Inflammation; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D051379:Mice