Mucosal Immunity: Its Role in Defense and Allergy

Abstract

The interface between the organism and the outside world, which is the site of exchange of nutrients, export of products and waste components, must be selectively permeable and at the same time, it must constitute a barrier equipped with local defense mechanisms against environmental threats (e.g. invading pathogens). The boundaries with the environment (mucosal and skin surfaces) are therefore covered with special epithelial layers which support this barrier function. The immune system, associated with mucosal surfaces covering the largest area of the body (200–300 m²), evolved mechanisms discriminating between harmless antigens and commensal microorganisms and dangerous pathogens. The innate mucosal immune system, represented by epithelial and other mucosal cells and their products, is able to recognize the conserved pathogenic patterns on microbes by pattern recognition receptors such as Toll-like receptors, CD14 and others. As documented in experimental gnotobiotic models, highly protective colonization of mucosal surfaces by commensals has an important stimulatory effect on postnatal development of immune responses, metabolic processes (e.g. nutrition) and other host activities; these local and systemic immune responses are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance. Characteristic features of mucosal immunity distinguishing it from systemic immunity are: strongly developed mechanisms of innate defense, the existence of characteristic populations of unique types of lymphocytes, colonization of the mucosal and exocrine glands by cells originating from the mucosal organized tissues (‘common mucosal system’) and preferential induction of inhibition of the responses to nondangerous antigens (mucosal tolerance). Many chronic diseases, including allergy, may occur as a result of genetically based or environmentally induced changes in mechanisms regulating mucosal immunity and tolerance; this leads to impaired mucosal barrier function, disturbed exclusion and increased penetration of microbial, food or airborne antigens into the circulation and consequently to exaggerated and generalized immune responses to mucosally occurring antigens, allergens, superantigens and mitogens.

Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 1 in Oxidative Burst Response to Toll-Like Receptor 5 Signaling in Large Intestinal Epithelial Cells

“…Recently, these cells have been shown to play an important role in host defense as well, producing proinflammatory mediators after the interaction with pathogenic microbes (28). In fact, stimulation of TLR4 in guinea pig gastric mucosal cells by H. pylori LPS activated NF-B within 30 min, followed by up-regulation of Nox1 activity within 8 h (11,14).…”

Immune response to gut Escherichia coli and susceptibility to adjuvant arthritis in the rats

“…(total number of animals: DA, n = 10; AO, n = 10). b For each rat strain the number of animals per group was 6 (total number of animals including non-immunized rats which were used as a control for fl ow cytometry analyses of lymph node cells: DA, n = 30; AO, n = 30).…”

“…Although it was shown that multiple genes contribute to rheumatoid arthritis (RA) susceptibility [1][2][3][4], it is believed that a combination of a specifi c genetic background and some environmental factors are required for the disease onset. The prevailing hypothesis involves the role of microbes and infection as possible factor s that could initiate the autoimmune process in genetically predisposed individuals [5,6]. In particular, numerous data indicate involvement of commensal microfl ora in the ethiopathogenesis of RA [7][8][9].…”

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

“…As the induction of allergic contact sensitivity reactions is rarely seen within these tissue, it is apparent that tolerance inducing immunological mechanisms are of primary importance within the gastrointestinal tract (61,62). Important features of the mucosal tissue which are implicated in providing this unique immunological privilege include a complex epithelial barrier system (63,64). Furthermore the capability to produce IgA antibodies and the property to develop Th2 helper cell responses to a lesser extent (Fig.…”