How food protein becomes recognized as an allergen remains a fundamental question. Previous studies indicated that the pathophysiology of food allergy is because of a skewed Th2 response to specific food glycoproteins. The focus has now shifted to understanding how a failure of regulatory mechanisms results in food allergy. This review summarizes the recent findings elucidating the small intestine's role in the pathophysiology of food allergy and the immune mechanisms of oral tolerance.
Gut homeostasis and immunity occur via a complex interplay of innate and adaptive immune responses. Immune exclusion is performed mainly by secretory IgA, although there are back-up mechanisms in place to induce oral tolerance when secretory IgA is lacking. Oral tolerance cannot occur in murine models lacking T regulatory cells, for which Foxp3+ is a key marker. Migration of Foxp3+ T cells from the mesenteric lymph nodes (MLNs) to the lamina propria occurs via gut-homing signals. Also in the MLNs are CD103+ dendritic cells, which drive the differentiation of Foxp3+ T cells in the presence of TGF-β and retinoic acid produced from dietary vitamin A. Lastly, microenvironmental signals from the microbiome can serve to enhance these interactions.
We have focused primarily on local immunologic variables that may affect the induction of oral tolerance in the gut and the mechanisms elucidated in animal models. However, many other variables such as genetics, commensal microbiota, and diet are likely to be important factors.
[Show abstract][Hide abstract] ABSTRACT: To cite this article: Pelkonen AS, Kuitunen M, Dunder T, Reijonen T, Valovirta E, Mäkelä MJ. Allergy in children: practical recommendations of the Finnish Allergy Programme 2008–2018 for prevention, diagnosis, and treatment. Pediatr Allergy Immunol 2012: 23: 103–116.
The Finnish Allergy Programme 2008–2018 is a comprehensive plan intended to reduce the burden of allergies. One basic goal is to increase immunologic tolerance and change attitudes to encourage health instead of medicalizing common and mild allergy symptoms. The main goals can be listed as to: (i) prevent the development of allergic symptoms; (ii) increase tolerance to allergens; (iii) improve diagnostics; (iv) reduce work-related allergies; (v) allocate resources to manage and prevent exacerbations of severe allergies, and (vi) reduce costs caused by allergic diseases. So far, the Allergy Programme has organized 135 educational meetings for healthcare professionals around Finland. These meetings are multidisciplinary meetings gathering together all healthcare professionals working with allergic diseases. Since the start of the program in spring 2008, more than 7000 participants have taken part. Educational material for patient care has been provided on special Web sites/therapeutic portals, which can be accessed by all physicians caring for allergic patients. Local Allergy Working Groups have been created in different parts of Finland. As a part of the Programme, a set of guidelines for child welfare clinics was prepared. Child welfare clinics have a key role in the screening of illnesses and providing advice to families with a symptomatic child. The guidelines aimed to facilitate pattern recognition and clinical decision making for public health nurses and doctors are described in this paper.
[Show abstract][Hide abstract] ABSTRACT: The incidence of food allergy in developed countries is rising at a rate that cannot be attributed to genetic variation alone. In this review, we discuss the environmental factors that may contribute to the increasing prevalence of potentially fatal anaphylactic responses to food. Decreased exposure to enteric infections due to advances in vaccination and sanitation, along with the adoption of high-fat (Western) diets, antibiotic use, Cesarean birth, and formula feeding of infants, have all been implicated in altering the enteric microbiome away from its ancestral state. This collection of resident commensal microbes performs many important physiological functions and plays a central role in the development of the immune system. We hypothesize that alterations in the microbiome interfere with immune system maturation, resulting in impairment of IgA production, reduced abundance of regulatory T cells, and Th2-skewing of baseline immune responses which drive aberrant responses to innocuous (food) antigens.
Seminars in Immunopathology 09/2012; 34(5):671-88. DOI:10.1007/s00281-012-0337-5 · 7.75 Impact Factor
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