STUDIES IN PROGRESSIVE IMMUNE KIDNEY DISEASE

进行性免疫性肾病的研究

• 批准号: 3152500
• 负责人: CURTIS B WILSON
• 金额: $ 12.19万
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152500
• 关键词: antibody formation; autoimmune disorder; basement membrane; clone cells; complement; complement fixation tests; delayed hypersensitivity; disease /disorder model; electron microscopy; glomerulonephritis; helper T lymphocyte; humoral immunity; immune complex; immunization; immunofluorescence technique; immunopathology; interleukin 2; interstitial nephritis; lymphocyte; macrophage; model design /development; monoclonal antibody; neutrophil; renal failure; suppressor T lymphocyte

Considerable information is available about the antibody mechanisms that initiate experimental and human renal injury. Despite this knowledge and the use of aggressive therapeutic maneuvers to modulate nephritogenic antibody responses, renal damage often progresses relentlessly to renal failure, necessitating costly and only partially satisfactory measures such as dialysis. Studies herein will examine the humoral and cellular processes leading to progression of immunologically-induced tubulointerstitial nephritis in the rat. This model has an apparent antibody-associated first stage, with sequential stages in which lymphocytes predominate and subsequently monocytes/macrophages, with fibrosis, become prominent. Studies are outlined to determine the major immunopathogenesis of these three stages and to understand how one stage influences the sequential evolution of the next. These include quantitative serum transfer experiments and complement depletion (also polymorphonuclear leukocyte depletion, if needed) to evaluate the first stage. A central question is whether the lymphocytes (predominately T helper cells) in the second stage may be sensitized by the initial injury so that the lesion becomes self-perpetuating. To answer this, selective cell proliferation assays in response to both immunizing and autologous tubular antigens will be done. In addition, subrenal capsule transfer using cells extracted from the active lesions (total cells or populations depleted of T cell subsets or B cells) will be used with or without in vitro antigen-specific propagation and the addition of specific antibody or tubular antigens. These studies coupled with modulation (by specific antisera) of the lymphocyte and macrophage stages will provide an overview of the interrelated facets in the evolution of this model of progressive immune renal injury. The production of the lymphocyte factor, interleukin-2, by the infiltrating cells will be studied since, in association with antigen and accessory cells, it could stimulate local propagation of T cells. Macrophage-produced interleukin-1 will be studied at it may relate to the fibrosis of the later stages of the lesion. An understanding of the elements responsible for the sequential evolution of this lesion and the steps necessary for their interruption will provide a basis for understanding progression and its manipulation in human immune renal injury.

有关抗体机制的大量信息 启动实验和人类肾脏损伤。 尽管知识和 使用侵略性治疗动作来调节肾脏源 抗体反应，肾脏损伤通常会无情地发展为肾脏 失败，需要成本高昂，只有部分令人满意的措施 作为透析。 这里的研究将检查体液和细胞 导致免疫学诱导的进展 大鼠的肾小管间质肾炎。 该模型有一个明显的 抗体相关的第一阶段，有顺序的阶段 淋巴细胞占主导地位，随后是单核细胞/巨噬细胞，具有 纤维化，变得突出。 概述了研究以确定主要 这三个阶段的免疫发病发生，并了解一个阶段 影响下一个的顺序演变。 这些包括 定量血清转移实验和补体耗竭（也是 如果需要的话，多形核白细胞耗竭）评估第一个 阶段。 一个核心问题是淋巴细胞是否（主要t） 在第二阶段的辅助细胞可能会因初始损伤而受到敏感 使病变变得自我延续。 要回答这个问题 响应免疫和自体的细胞增殖测定 将进行管状抗原。 另外，下肾上腺囊转移 使用从活性病变中提取的细胞（总细胞或种群 T细胞子集或B细胞的耗尽）将使用或不使用 体外抗原特异性繁殖以及添加特定抗体或 管状抗原。 这些研究与调节结合（通过 淋巴细胞和巨噬细胞阶段的抗血清将提供概述 在这种进步模型的演变中相互关联的方面的 免疫肾脏损伤。 淋巴细胞因子的产生， 介绍浸润细胞的白介素-2将被研究 它与抗原和辅助细胞相关联，它可以刺激局部 T细胞的传播。 将研究巨噬细胞生产的白介素-1 它可能与病变后期的纤维化有关。 一个 理解负责顺序演变的要素 这种病变和中断所需的步骤将提供 理解进展及其在人类免疫中的操纵的基础 肾脏受伤。