IMMEDIATE HYPERSENSITIVITY RESPONSES--CONTROL IN PARASITIC HELMINTH INFECTIONS

虽然血液和组织嗜酸性粒细胞增多是大多数侵袭性疾病的特征 蠕虫感染、嗜酸性粒细胞在炎症中的全面作用 对寄生虫的反应或保护性反应尚不清楚。 不断积累的证据表明，嗜酸性粒细胞，在一个 在进化的基础上，已被选择为具有细胞毒性的能力 对寄生虫来说是一种主要的防御措施 针对这些生物的保护性免疫反应，尽管 嗜酸性粒细胞相关的病理常见于特应症和 蠕虫感染。然而，无论他们扮演什么角色，理解 嗜酸性粒细胞反应是如何被调节的，被招募到 炎症并在丝虫感染和其他疾病中激活 病理状态是这个项目的一个具体目标。 人类蠕虫感染的一个显著和共同的特征是 外源性IgE和IgG4抗体的优势升高 抗原。而IgE的优先升高则被认为是 负责调解即刻超敏反应 与嗜碱性粒细胞和肥大细胞上的高亲和力FcER结合，平行 IgG4和IgE的升高被认为是一种 免疫球蛋白E介导的即刻超敏反应的控制元件 通过阻断可溶变应原对包被IgE的肥大的访问 细胞。基于此观察到的优先和平行的 IgE和IgG4亚型的反应，可以预测 这两种同工型的调节可能类似和不同于 其他免疫球蛋白亚类。因此，该项目这一部分的目的是， 是为了了解这两种同工型的调控。

While blood and tissue eosinophilia is a hallmark of most invasive helminth infections, the full role of the eosinophil in the inflammatory reaction or the protective responses to parasites is not understood. Evidence continues to accumulate showing that the eosinophil, on an evolutionary basis, has been selected for its capacity to be cytotoxic for helminth parasites and is thereby a major defense in the host's protective immune response against these organisms, although eosinophil-associated pathology is found frequently in both atopy and helminth infections. Whatever their role, however, an understanding of how eosinophil responses are regulated, recruited to sites on inflammation and activated in filarial infections and other pathological states is one specific aim of this project. A remarkable and common feature of human helminth infections is the predominant elevations of IgE and IgG4 antibodies directed to exogenous antigens. While the preferential elevation of IgE is felt to be responsible for mediating immediate hypersensitivity reactions through binding to high affinity FcER on basophils and mast cells, the parallel increase of IgG4 with that of IgE has been postulated to act as a control element for the IgE-mediated immediate hypersensitivity reaction by blocking the access of the soluble allergens to the IgE coated mast cells. Based on this observation of a preferential and parallel response by IgE and IgG4 isotypes, it might be predicted that regulation of these two isotypes may be similar and distinct from the other IgG subclasses. The purpose of this part of the project, thus, is to understand the regulation of these two isotypes.