Control of immediate hypersensitivity responses in parasitic and other diseases

卫生学假说表明，寄生虫感染调节宿主免疫反应，减少特应性，但其他数据表明，寄生虫感染可能会诱导过敏反应。为了研究寄生虫编码的抗原和庄园空气变应原同源物之间的分子、结构和免疫学关系，用两组不同的抗原(原肌球蛋白或谷胱甘肽-S-转移酶)比较了丝虫感染和丝虫未感染的特应症患者血清中寄生虫和变应原特异性的Ig E、Ig G和Ig G。这两组抗原在氨基酸水平上有高度的一致性，重叠预测了三维结构。用对原肌球蛋白或GST过敏的人的血清致敏的嗜碱性粒细胞在触发其寄生虫同源物时释放组胺，实验感染特定蠕虫的动物(非人类灵长类动物或小鼠)诱导IgE抗体，该抗体与空气变应原同源物在免疫和功能上发生交叉反应。 为了系统地研究变应原和病原体(蠕虫、原虫、真菌和细菌)蛋白质之间的结构关系，我们将499个分子定义的过敏原的氨基酸序列与15个已知病原体的预测蛋白质组进行了比较，其中包括Th2诱导蠕虫和Th1诱导原虫以及人类。过敏性评估是基于公众可访问的数据库中的IgE流行率。我们在蠕虫、原生动物、真菌和人类的蛋白质中发现了常见过敏原的多种同源物，但没有发现细菌的同源物。在过敏人群中，没有同源的过敏原或序列保守水平有限的过敏原是最具过敏性的，表现出较高的IgE流行率。过敏性和氨基酸保守水平之间存在反向关系，这表明过敏性可能与抗原的相对“唯一性”有关，即免疫原性，而序列相似性导致免疫耐受性。 评估寄生虫抗原敏化在生命早期的发生情况，因为这可能对感染和未感染母亲的新生儿脐带血中寄生虫抗原刺激的脐带血中的过敏发展和对感染性、干扰素-γ和IL-4反应的敏感性有重要影响。有证据表明，在感染母亲的新生儿中，表达干扰素-γ和表达IL-4的CD4+T细胞(和表达IL-4的嗜碱性粒细胞)的频率高于未感染母亲的新生儿，这为宫内致敏蠕虫抗原提供了证据，并增加了感染的免疫效应始于胎儿的可能性。

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.