本文關(guān)鍵詞： 供體脾淋巴細胞 凋亡 受體 肝臟 肝臟抗原遞呈細胞 吞噬作用 細胞因子　出處：《第一軍醫(yī)大學》2006年博士論文　論文類型：學位論文

【摘要】：免疫耐受是解決移植排斥反應(yīng)的根本方法之一。目前采用的耐受誘導方法多以中央和外周耐受理論為基礎(chǔ)形成，但由于各種原因尚未取得預(yù)想的結(jié)果。凋亡是生物體內(nèi)的基本生理現(xiàn)象之一，對于維持機體內(nèi)在平衡非常關(guān)鍵。研究已發(fā)現(xiàn)，，凋亡是機體維持免疫系統(tǒng)穩(wěn)定的重要作用機制，而且凋亡細胞對炎性反應(yīng)的抑制性調(diào)節(jié)作用是一種主動的過程：凋亡細胞通過分泌趨化因子、變換細胞膜表面特征“eat-me”分子，誘導吞噬細胞對其進行清除，同時在清除過程中通過巨噬細胞等分泌炎癥抑制性因子，如TGFβ、IL-10、PGE_2等造成一個特殊的免疫微環(huán)境。正常生理狀態(tài)下，此過程可以促使相關(guān)淋巴細胞對其特征性抗原識別激活后產(chǎn)生免疫耐受，而不是引起炎性免疫應(yīng)答。根據(jù)凋亡細胞能夠主動引起免疫耐受這一現(xiàn)象，孫爾維等首次提出利用供體凋亡細胞輸注受體誘導供體特異性免疫耐受的理論設(shè)想。由此，本課題組前期研究開展了供體凋亡脾淋巴細胞對大鼠心臟、肝臟移植模型誘導耐受的實驗研究，發(fā)現(xiàn)一定數(shù)量的供體凋亡脾淋巴細胞預(yù)輸注可以誘導大鼠心、肝臟移植模型產(chǎn)生特異性免疫耐受，延長移植存活時間。該發(fā)現(xiàn)初步驗證了孫爾維等的理論設(shè)想，但對于供體凋亡細胞輸注如何誘導機體產(chǎn)生非特異性免疫耐受，其內(nèi)在作用的關(guān)鍵環(huán)節(jié)和機制是什么，都尚未可知。同時，類似的相關(guān)機制研究，國內(nèi)外都未有報道可以用來參照和解釋，而了解供體凋亡細胞誘導移植耐受的內(nèi)在機制對于深入掌握該理論的中心環(huán)節(jié)、進一步完善該理論設(shè)想，進而指導更有效地實現(xiàn)耐受誘導有
[Abstract]:Immune tolerance is one of the fundamental methods to solve the allograft rejection. Most of the current tolerance induction methods are based on the central and peripheral tolerance theory. However, due to various reasons, the expected results have not been obtained. Apoptosis is one of the basic physiological phenomena in organisms, which is very important to maintain the balance in the body. It has been found that apoptosis is an important mechanism for maintaining the stability of the immune system. Moreover, the inhibitory effect of apoptotic cells on inflammatory response is an active process: apoptotic cells induce phagocytes to clear them by secreting chemokines, transforming "eat-me" molecules on the surface of cell membranes, and inducing phagocytes to clear them. At the same time, during the process of clearance, inflammatory inhibitory factors such as TGF 尾 -IL-10 and PGE-2 were secreted by macrophages, which resulted in a special immune microenvironment. This process can induce the associated lymphocytes to develop immune tolerance after activation of their characteristic antigen recognition rather than inflammatory immune response, according to the phenomenon that apoptotic cells can actively induce immune tolerance. Sun Erwei et al proposed for the first time a theoretical idea of donor-specific immune tolerance induced by donor apoptotic cell infusion. Experimental study on tolerance induced by liver transplantation model showed that a certain number of donor apoptotic splenic lymphocytes preinfused could induce rat heart and liver transplantation model could produce specific immune tolerance. The findings preliminarily verify Sun Erwei's theory, but what is the key link and mechanism of the intrinsic role of donor apoptotic cell infusion in inducing nonspecific immune tolerance. At the same time, there is no domestic and foreign report on similar mechanisms that can be used for reference and explanation, and understanding the intrinsic mechanism of donor apoptosis induced transplantation tolerance is central to a deeper understanding of this theory. Further improve the theoretical assumption, and then guide the more effective implementation of tolerance induction.
【學位授予單位】：第一軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R392.4

【引證文獻】

相關(guān)碩士學位論文 前1條

1 丘昶儒;預(yù)輸注5-Fu處理的同種異基因淋巴細胞誘導大鼠肝移植免疫耐受的初步研究[D];廣州醫(yī)學院;2010年

本文編號：1496661