IMMEDIATE HYPERSENSITIVITY RESPONSES--CONTROL IN PARASITIC HELMINTH INFECTIONS

立即超敏反应——控制寄生虫感染

• 批准号: 6160796
• 负责人: T B NUTMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160796
• 关键词: cytokine; enzyme linked immunosorbent assay; eosinophil; flow cytometry; helminthiasis; helminthic antigen; host organism interaction; human tissue; immediate hypersensitivity; immunoglobulin E; immunoglobulin G; immunoregulation; inflammation

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.

虽然血液和组织嗜酸性粒细胞增多是大多数侵袭性 蠕虫感染，嗜酸性粒细胞在炎症中的充分作用， 对寄生虫的反应或保护性反应尚不清楚。 越来越多的证据表明，嗜酸性粒细胞，在一个 进化的基础上，已被选定的能力，是细胞毒性 寄生虫，因此是一个主要的防御在主机的 针对这些生物体的保护性免疫反应，尽管 嗜酸性粒细胞相关的病理常见于特应性和 蠕虫感染 无论他们的角色是什么， 嗜酸性粒细胞的反应是如何调节的， 炎症和激活丝虫感染和其他 病理状态是该项目的一个具体目标。 人类蠕虫感染的一个显著和共同特征是 IgE和IgG4抗体主要升高，针对外源性 抗原 虽然IgE的优先升高被认为是 负责介导速发型超敏反应， 与嗜碱性粒细胞和肥大细胞上的高亲和力FcER结合， 据推测，IgG4随着IgE的增加而增加，起到了 IgE介导的速发型超敏反应的控制元件 通过阻断可溶性过敏原接近IgE包被的柱 细胞 基于对一个优先和平行的 通过IgE和IgG4同种型的反应，可以预测， 这两种同种型的调节可能相似，也可能不同于 其他IgG亚类。 因此，这部分项目的目的是， 就是了解这两种同种型的调节。