IMMUNOPATHOGENESIS OF LYMPHATIC FILARIASIS

目前围绕丝虫性炎症的免疫学范式 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， 如我们现在证明的丝虫病的研究是可行的， 一个不寻常的机会来研究免疫系统的致病机制， 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、活组织和外周血 从感染的人身上分离出来。巴西班氏病流行区将成为 同时研究。 患者最初将被分为3组 根据临床和当前感染情况， 以下3个具体的实验目的：1）确定T细胞受体 (TCR)通过比较TCRVb库， 感染组织和血液中的同一个人; 2）确定 通过比较细胞因子水平， 与局部疾病相关的细胞因子mRNA水平， 在不同的临床组活检;和3）检查的效果 清除剂量为 杀大型丝虫剂根据我们公布的大量初步数据，我们 相信所有W。bancrofti感染的病人有疾病， 任何明显的临床表现 因此电流 丝虫病患者根据临床或 微丝蚴状态可能不适合了解当地 免疫病理学事件。 我们希望，由于拟议的 工作，能够提供一个相关的框架， 对疾病进行分类，以便能够制定有针对性的战略， 免疫干预 此外，调查结果可能广泛 适用于其他人体蠕虫的局部组织反应。

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.