IMMUNOREGULATION AND IMMUNE RECOGNITION IN FILARIASIS AND NONFILARIAL DISEASES

丝虫病和非丝虫病的免疫调节和免疫识别

• 批准号: 2566718
• 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/2566718
• 关键词: CD antigens; MHC class II antigen; anergy; clinical research; disease /disorder proneness /risk; eosinophil; filariasis; genetic polymorphism; genotype; helminthiasis; helminthic antigen; helper T lymphocyte; histocompatibility typing; human subject; immunity; immunogenetics; immunoregulation; interleukin 10; interleukin 5; leukocyte activation /transformation; onchocerciasis; racial /ethnic difference

The purpose of this project is to delineate the mechanisms involved in regulating immune responses in filarial and nonfilarial disease states. New models for examining in vitro the early immune response to parasite antigens have been developed; so that naive (CD45 RA+) cells can be primed for the production of cytokines in response preferentially to parasite antigen upon restimulation. The data indicate that helminth antigens are capable of driving the immune response toward the production of IL-4, IL-5 and IL-10. Using selected recombinant filarial antigens, the role the antigens themselves play in the induction of a Th2 response and the B-cell response it subsequently influences (IgE/IgG4) has also been studied. Similarly, new ways of assessing eosinophil activation have also been developed. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of the production of the antiproliferative cytokine, IL-10. This IL-10 is preferentially induced by stage-specifiic (microfilarial) antigens; the effect of IL-10 is, in part, mediated by the modulation of the costimulatory molecules, CD80/CD86 and its ligand, CD28. The genetics underlying susceptibility and resistance to filarial infection has been studied by HLA Class II typing along with allotyping. A particular KM allotype has been shown to be associated with resistance to onchocerciasis in Afro-Ecuadorian populations, and an HLA Class II haplotype, DRB1*08042-DQA1*0401-DQB1*0402, is associated with resistance in the Amerindian population. Further, a new TNF-alpha promoter polymorphism (TNFAp4) has also been identified and studied at the population level.

本项目的目的是阐明 调节丝虫病和非丝虫病状态下的免疫反应。 体外检测寄生虫早期免疫应答的新模型 已经开发了抗原;因此可以将幼稚（CD 45 RA+）细胞 为细胞因子的产生做好了准备， 寄生虫抗原。 数据显示蠕虫 抗原能够驱动免疫应答， IL-4、IL-5和IL-10。使用选定的重组丝虫抗原， 抗原本身在诱导Th 2应答中的作用 它随后影响的B细胞反应（IgE/IgG 4）也 本文研究了 同样，评估嗜酸性粒细胞活化的新方法 也得到了发展。 免疫调节研究已经检查了抗原特异性免疫应答的现象。 微丝蚴血症患者的无反应性，通过显示这种无反应性是 抗增殖细胞因子IL-10的产生。 这架IL-10 优先由阶段特异性（微丝蚴）抗原诱导; IL-10的作用部分是通过调节 共刺激分子，CD 80/CD 86及其配体，CD 28。 丝虫易感性和抗性的遗传学基础 通过HLA II类分型沿着同种异型分型研究了感染。 一种特殊的KM同种异型已被证明与耐药性有关 非裔厄瓜多尔人群中的盘尾丝虫病，以及HLA II类 单倍型DRB 1 *08042-DQA 1 *0401-DQB 1 *0402与耐药相关 在美洲印第安人中。 此外，新的TNF-α启动子 多态性（TNFAp 4）也已确定和研究， 人口水平。