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THE INFLAMMATORY RESPONSE OF ALLOGRAFT REJECTION

同种异体移植排斥的炎症反应

基本信息

批准号：
3151681
负责人：
PEKKA J HAYRY
金额：
$ 8.09万
依托单位：
UNIVERSITY OF HELSINKI
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-06-01 至 1986-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3151681
关键词：
B lymphocyte T lymphocyte cell mediated cytotoxicity chemotherapy histocompatibility antigens homologous transplantation human subject human tissue hybridomas immunochemistry immunotoxicity inflammation kidney transplantation macrophage monocyte tissue /cell culture

项目摘要

The aim of this investigation is to analyze the inflammatory pathways of allograft rejection. Rat experiments will guideline subsequent human studies. We will define (a) which cellular components in different allografts are antigenic, i.e., express transplantation antigens, and (b) which of them are immunogenic, i.e., elicit an immune response, (c) analyze the cellular activation cascade of renal allograft rejection at the site of inflammation and relate the in situ events to changes in the central lymphatic system of the host, (d) investigate how does the host immune response regulate the in situ inflammatory events, (e) define the different cellular and humoral effector mechanisms operative in situ during allograft rejection and (f) investigate how is the inflammation modified by tolerogenic schedules and by drugs with known site(s) of action. These findings will be applied to man by using fine needle aspiration biopsy, transplant aspiration cytology and related cytological methods. We will (g) analyze how is the antigenic anatomy of an allograft modified as a consequence of transplantation, relate these alterations to the immunosuppressive treatment, define how is the inflammatory response modified as a consequence of immuno-suppression, which are the different cellular inflammatory patterns leading to allograft rejection in man and what are the histological correlates of these cytological patterns. Finally, preliminary experiments are made to explore the cellular effector systems operative in human renal transplant rejection. Once the structure of inflammation and the mechanisms regulating the inflammatory response are known it is possible to develop a right strategy to counteract the inflammatory response.

这项调查的目的是分析炎症反应的途径同种异体排斥反应。大鼠实验将指导后续的人类学习。我们将定义(A)在不同的同种异体移植物是抗原性的，即表达移植抗原，以及(B) 其中哪些是免疫原性的，即引起免疫反应，(C)分析同种异体肾移植排斥反应的细胞活化级联反应炎症并将原位事件与中央动脉的变化联系起来宿主的淋巴系统，(D)调查宿主如何免疫反应调节原位炎症事件，(E)定义不同的同种异体移植中原位操作的细胞和体液效应机制排斥反应和(F)研究炎症是如何通过耐受表和用药部位已知(S)的作用。这些结果将通过使用细针抽吸活组织检查应用于人类，移植抽吸细胞学及相关细胞学方法。我们会 (G)分析如何将同种异体移植物的抗原性解剖修改为移植的后果，将这些变化与免疫抑制治疗，定义炎症反应是如何的作为免疫抑制的结果进行修改，这是不同的导致同种异体移植排斥反应的细胞炎性模式这些细胞学模式的组织学相关性是什么？最后对细胞效应器进行了初步的实验研究。人体肾移植排斥反应系统的研究。一旦这个结构炎症和调节炎症反应的机制是我们知道有可能制定一个正确的战略来抵消炎症反应。