NOD鼠外周免疫耐受机制异常的研究

发布时间：2018-01-05 15:14

本文关键词：NOD鼠外周免疫耐受机制异常的研究　出处：《吉林大学》2007年硕士论文　论文类型：学位论文

【摘要】： 1型糖尿病(T1DM)是一种病因尚待阐明的自身免疫病。其发病机制虽然不完全清楚,但已经证明与自身免疫反应密切相关。自身免疫病是由于机体免疫系统丧失了对自身抗原成分的免疫耐受而导致的。自身耐受可分为中枢耐受和外周耐受。由于中枢耐受机制并不能保证所有自身反应性淋巴细胞的完全清除,因此需要外周免疫耐受机制的存在以保证免疫系统对自身成分不发生免疫应答。本实验以10周龄NOD小鼠为研究对象,通过对其外周免疫耐受状态的研究来探索T1DM的发病机制。主要从以下几方面进行研究:1.检测T1DM发生情况:血糖、尿糖的检测,血清中胰岛素自身抗体(IAA)水平,胰腺的组织学观察。2.外周耐受异常机制的研究:脾脏细胞体外增殖能力,脾脏细胞因子分泌水平,脾脏内CD4+CD25+调节性T细胞(Treg)水平,脾细胞Foxp3 mRNA的表达情况。结果表明:10周龄NOD小鼠尚没有出现典型的糖尿病症状,但胰岛内有大量炎细胞浸润,处于前糖尿病阶段。NOD小鼠存在外周耐受的异常:脾脏淋巴细胞增殖缺陷,Th1/Th2失衡;CD4+CD25+Treg对效应T细胞水平的相对升高,可能抑制了T细胞功能,致使NOD鼠没有发生糖尿病。
[Abstract]:Type 1 diabetes mellitus ( T1DM ) is an autoimmune disease which has yet to be clarified . Its pathogenesis is not completely clear , but it has been shown to be closely related to autoimmune response . Self - tolerance can be divided into central tolerance and peripheral tolerance because of the loss of immune tolerance to its own antigen components . Self - tolerance can be divided into central tolerance and peripheral tolerance . Since the central tolerance mechanism does not guarantee the complete elimination of all self - reactive lymphocytes , the presence of peripheral immune tolerance mechanism is required to ensure that the immune system does not immune response to its own components . In this study , the pathogenesis of T1DM was studied by the study of peripheral immune tolerance of 10 - week - old female mice . The results were as follows : 1 . Detection of T1DM : Blood sugar , urine sugar , serum insulin self - antibody ( IAA ) level and pancreas histological observation . The results showed that there were no typical diabetic symptoms in the 10 - week - old diabetic mice , but there was a large number of inflammatory cell infiltration in the islets of the islets in the pre - diabetes stage . There was an abnormal peripheral tolerance : the proliferation of splenic lymphocytes , the imbalance of Th1 / Th2 , the relative elevation of CD4 + CD25 + Treg on effector T cell levels , and the possible inhibition of T cell function , which resulted in the absence of diabetes .

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R392

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