Control of immediate hypersensitivity responses in parasitic and other diseases

卫生假说认为寄生虫感染可以调节宿主的免疫反应并降低特应性，但其他数据表明寄生虫感染可能引起过敏反应。为了研究寄生虫编码抗原和空气过敏原同源物的分子、结构和免疫学关系，我们使用两组不同的抗原（原肌球蛋白或谷胱甘肽-s转移酶（GSTs））比较了丝虫病感染和未感染丝虫病的特应性个体血清中寄生虫和过敏原特异性IgE、IgG和IgG。这两组抗原在氨基酸水平上具有高度的同一性，并且重叠预测了三维结构。嗜碱性粒细胞被原肌球蛋白或GST过敏个体的血清致敏，当触发它们的寄生虫同源物时，它们会释放出类似的组胺，实验中感染特定蠕虫的动物（非人灵长类动物或小鼠）会诱导IgE抗体，这些抗体在免疫和功能上与空气过敏原同源物发生交叉反应。

The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy, but other data suggest parasitic infections may induce allergic responsiveness. To examine the molecular, structural, and immunologic relationships parasite-encoded antigens and manor aeroallergen homologues, parasite- and allergen-specific IgE, IgG, and IgG in sera of filaria-infected and filarial-uninfected atopic individuals were compared using 2 different distinct sets of antigens (tropomyosins or glutathione-S-transferases (GSTs)). For both sets of antigens there was a high degree of identity at the amino acid level, and overlapping predicted 3-dimensional structures. Basophils sensitized with sera from individuals allergic to tropomyosin or GST released histamine similarly when triggered their parasite homologue and animals (non-human primates or mice) infected experimentally with particular helminths induced IgE antibodies that cross-reacted immunologically and functionally with the aeroallergen homologue. To examine systematically the structural relationships among allergens and proteins of pathogens (helminths, protozoans, fungi and bacteria) as they relate to allergenicity, we compared the amino acid sequence of 499 molecularly-defined allergens with the predicted proteomes of fifteen known pathogens, including Th2 inducing helminths and Th1-inducing protozoans, and humans. Allergenicity was assessed based on IgE prevalences using publicly accessible databases. We found multiple homologues of common allergens among proteins of helminths, protozoans, fungi and humans, but not of bacteria. Allergens without homologues or those with limited levels of sequence conservation were the most allergenic displaying high IgE prevalences in the allergic population. There was an inverse relationship between allergenicity and amino acid conservation levels suggesting that allergenicity may be associated with the relative "uniqueness" of an antigen, i.e. immunogenicity, while sequence similarity leads to immunological tolerance. To assess how early in life parasite antigen sensitization occurs as this may have important effects on the development of allergy and on susceptibility to infectious, interferon-gamma and IL-4 responses in A. lumbricoides antigen-stimulated cord blood from newborns of infected and noninfected mothers by flow cytometry. There was evidence of higher frequencies of both IFN-gamma-expressing and IL-4-expressing CD4+ T cells (and IL-4 expressing basophils) in newborns of infected mothers than in newborns of noninfected mothers providing evidence of in utero sensitization helminth antigens and raising the possibility that the immunological effects of infection start in the fetus.