IMMUNOPATHOGENESIS OF LYMPHATIC FILARIASIS

淋巴丝虫病的免疫发病机制

• 批准号: 2855990
• 负责人: DAVID O FREEDMAN
• 金额: $ 23.37万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2855990
• 关键词: T cell receptor; T lymphocyte; Wuchereria; antigen receptors; cell adhesion; cell cell interaction; clinical research; cytokine; enzyme linked immunosorbent assay; filariasis; helminthic antigen; histocompatibility antigens; histopathology; human subject; human tissue; immunopathology; leukocyte activation /transformation; lymphatic disorder; pathologic process; polymerase chain reaction; receptor expression; surface antigens; tissue /cell culture

The current immunological paradigms surrounding filarial inflammation have evolved almost exclusively from studies of peripheral immune responses. In humans, examination of tissue at the actual site of disease activity, such as we now shown to be feasible for the study of filariasis, provides an unusual opportunity to examine pathogenetic mechanisms of the immune response to a human helminthic pathogen. Because there is no adequate animal model of bancroftian filariasis, biopsy tissue and peripheral blood from infected humans in a W. bancrofti endemic area of Brazil will be simultaneously studied. Patients will be initially classified into 3 groups based on clinical and current infections in order to carry out the following 3 specific experimental aims: 1) Determine the T-cell Receptor (TCR) repertoire at the site of disease by comparing TCR Vb repertoires in infected tissue and in blood of the same individual; 2) Determine the cytokines relevent to local disease by comparing levels of cytokines relevent to local disease by comparing levels of cytokine mRNA from biopsies in the different clinical groups; and 3) Examine the effect of total body worm burden from study subject with a clearing dose of macrofilaricide. Based on our substanstial published preliminary data, we believe that all W. bancrofti infected patients have disease irrespective of the presence of any overt clinical manifestations. Thus, the current polar polar classification of filariasis patients according to clinical or microfilaria status may not be appropriate for understanding local immunopathologic events in tissue. We hope, as a result of the proposed work, to be able to provide a relevent framework for staging and classifying disease in order to be able to develop targetted strategies for immunotherapeutic intervention. Moreover, the findings may be broadly applicable to local tissue reactions in other human helminths.

当前围绕丝虫炎症的免疫学范式 几乎完全是从外周免疫反应的研究中进化而来的。 在人类中，检查疾病活动实际部位的组织， 例如我们现在证明对于丝虫病的研究是可行的，提供 这是检查免疫致病机制的一个不寻常的机会 对人类蠕虫病原体的反应。 因为没有足够的 班氏丝虫病动物模型、活检组织和外周血 来自巴西班克罗夫蒂流行区的受感染人群将 同时学习。 患者最初将被分为 3 类 根据临床和当前感染情况进行分组，以便进行 以下 3 个具体实验目的： 1) 确定 T 细胞受体 通过比较疾病部位的 TCR Vb 指令集来确定疾病部位的 (TCR) 指令集 同一个体的受感染组织和血液； 2）确定 通过比较细胞因子水平来确定与局部疾病相关的细胞因子 通过比较细胞因子 mRNA 水平与局部疾病相关 不同临床组的活检； 3) 检查效果 研究对象的全身蠕虫负荷，清除剂量为 杀大丝虫剂。根据我们已发布的大量初步数据，我们 相信所有班克罗夫氏菌感染的患者都患有疾病，无论 是否存在任何明显的临床表现。 因此，当前 丝虫病患者根据临床或极地分类 微丝蚴状况可能不适合了解当地情况 组织中的免疫病理事件。 我们希望，由于提议的结果 工作，能够为分期和提供相关框架 对疾病进行分类，以便能够制定有针对性的策略 免疫治疗干预。 此外，研究结果可能广泛 适用于其他人类蠕虫的局部组织反应。