IMMUNOREGULATION AND IMMUNE RECOGNITION IN FILARIASIS AND NON-FILARIAL DISEASES

丝虫病和非丝虫病的免疫调节和免疫识别

• 批准号: 5200411
• 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/5200411
• 关键词: CD antigens; Filarioidae; MHC class II antigen; adolescence (12-20); anergy; child (0-11); cytokine; eosinophil; filariasis; helminthiasis; helminthic antigen; helper T lymphocyte; human subject; human tissue; interferon gamma; interleukin 5; leukocyte activation /transformation; microorganism immunology; onchocerciasis; phosphoprotein phosphatase; plaque assay; stainings

The purpose of this project is to delineate the mechanisms involved in regulating immune responses in filarial and nonfilarial disease states. 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, made by both monocytes and CD4+ cells (of the Th2 type). The phenotypic characterization of these Th2 CD4+ cells has shown them to be CD45RO+CD27-; a novel method for intracellular staining for cytokines has shown that IL-5 and interferon gamma are the best discriminators of Th2 and Th1 T-cell subsets. 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 been studied. Similarly, new ways of assessing eosinophil activation have also been developed. Clinical epidemiological and parasitological assessment of individuals who are "putatively immune" to either onchocerciasis or lymphatic filariasis have been identified. These individuals very clearly mount augmented cellular responses to parasite antigens and, for those immune to onchocerciasis, responses to a recombinant antigen (OV20/11) have been associated with resistance, and suggests a mechanism for protection. 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 identified as correlating with resistance to infection. Also, a number of novel DQ and DP alleles have been identified.

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。 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， 单核细胞和CD 4+细胞（Th 2型）。表型 对这些Th 2 CD 4+细胞的表征表明它们是 CD 45 RO + CD 27-;细胞内细胞因子染色的新方法， 显示IL-5和干扰素γ是Th 2的最佳鉴别剂 和Th 1 T细胞亚群。 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 及其随后影响的B细胞反应（IgE/IgG 4） 本文研究了 同样，评估嗜酸性粒细胞活化的新方法 也已经开发了。 对个人的临床流行病学和寄生虫学评估 对盘尾丝虫病或淋巴结炎具有“脓性免疫”的人 丝虫病已被发现。 这些人显然 增强对寄生虫抗原的细胞应答， 对于盘尾丝虫病，对重组抗原（OV 20/11）的应答已经被证实是 与耐药性有关，并提出了一种保护机制。 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。 一种特定的KM同种异型已被鉴定为与 抵抗感染。 此外，一些新的DQ和DP等位基因具有 被识别。