Control of immediate hypersensitivity responses in parasitic and other diseases

卫生假说认为寄生虫感染调节宿主免疫反应并降低特应性，但其他数据表明寄生虫感染可能诱导过敏反应。为了研究寄生虫编码的抗原和主要的空气过敏原同源物之间的分子，结构和免疫学关系，寄生虫和过敏原特异性IgE，IgG和IgG在丝虫感染和丝虫未感染的特应性个体的血清中进行了比较，使用多套寄生虫抗原及其空气过敏原同源物。 对于所有的抗原集有一个高度的同一性在氨基酸水平上，重叠预测的3-dimensional structures .We发现，丝虫感染增加了针对屋尘螨和蟑螂的血清学流行IgE，但不是针对梯牧草，似乎是相关的过敏原和蠕虫蛋白之间的结构相似性的存在。IgE ELISA证实，感染的个人有较高的IgE患病率，这些重组过敏原，在蠕虫中有同源物。感染蠕虫Heligmosomoides polygyrus的小鼠显示IgE水平升高，并对寄生虫中的同源物过敏原进行阳性皮肤试验。 我们已经将这些发现扩展到T细胞水平。 使用来自患有丝虫感染（有或没有过敏性疾病）的个体的细胞和来自未感染个体（有或没有过敏性疾病）的细胞，我们已经表明寄生虫抗原（及其空气过敏原直系同源物）驱动丝虫感染中的CD 4 + IL-4/IL-13主导的应答，当使用多参数流式细胞术或多重细胞因子测量测量时，当受试者也过敏时，该应答增强。

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 between parasite-encoded antigens and major aeroallergen homologues, parasite- and allergen-specific IgE, IgG, and IgG in sera of filaria-infected and filarial-uninfected atopic individuals were compared using multiple sets of parasite antigens and their aero-allergen homologues. For all sets of antigens there was a high degree of identity at the amino acid level, and overlapping predicted 3-dimensional structures .We found that filarial infection increased the serological prevalence IgE directed against house dust mite and cockroach, but not against timothy grass that appeared to be related to the presence of structural similarity between the allergens and the helminth proteins. IgE ELISA confirmed that infected individuals had higher IgE prevalences to those recombinant allergens that had homologues in helminths. Mice infected with helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologues in the parasite. We have extended these findings to the level of the T cell. Using cells from individuals with filarial infection (with or without allergic disease) and those from uninfected individuals (with or without allergic disease), we have shown that parasite antigen (and their aero-allergen orthologues) drives a CD4+ IL-4/IL-13 dominated response in filarial infection that is augmented when the subject is also allergic when measured using multiparameter flow cytometry or multiplexed cytokine measurements.