【作者】 王少敏；

【导师】 台桂香；

【作者基本信息】 吉林大学 ， 免疫学， 2004， 硕士

【摘要】 自身免疫性疾病是机体在内因、外因共同作用下，机体的自身免疫应答失控、反应过度，直接或间接的破坏自身组织，并引起相应器官病变或临床症状的一类疾病。系统性红斑狼疮（SLE）和原发性胆汁性肝硬化（PBC）是自身免疫性疾病的两种不同类型，是由于T细胞亚群比例失调，体内Th1/Th2细胞之间比例失衡。自身反应性T细胞增殖，导致B细胞活化产生大量自身抗体，形成免疫复合物，对机体免疫系统产生损伤，导致机体细胞免疫功能和体液免疫功能失调，引起自身免疫性疾病。 本实验通过测定吉林大学第一医院及地矿医院收治的30名SLE患者和30名PBC患者的血清中自身抗体水平和免疫荧光模式，血清循环免疫复合物（CIC）、C反应蛋白（CRP）、免疫球蛋白（IgG、IgA、IgM）、补体（C3、C4）含量及其部分患者外周血单个核细胞分泌的细胞因子（IL-2、TNF-α、IFN-γ、IL-4）的水平，与正常对照组相比较，说明自身免疫病的发病是由于免疫系统在内因、外因作用下，机体免疫调节失衡而导致的免疫系统损伤。 SLE患者是以多克隆B细胞活化和产生多种自身抗体为特征的全身性免疫性疾病，本组实验中SLE患者中血清含有多种自身抗体，其中dsDNA抗体与疾病的活动性明显相关，是SLE的特异性抗体。血清中高浓度的C反应蛋白显示SLE患者免疫功能紊乱，易并发感染，且与疾病的活动性相关。文献中报道的免疫球蛋白升高在本文中未能体现，而补体含量的下降证实SLE患者体内存在补体系统的激活，免疫功能损伤。SLE患者外周血单个细胞分泌的细胞因子检测IL-2，TNF-α，IFN-γ，明显低于正常对照组，而IL-4水平显著高于正常对照组，这些研究结果表明SLE患者体内存在細胞免疫异常，体内Th亚群平衡偏离，Th1/Th2功能失调，Th2功能亢进，而Th1功能不足，从而导致体内细胞因子比例失衡，B细胞过度活化，产生多种自身抗体，导致机体免疫功能损伤。 PBC患者是自身免疫介导的一种慢性胆管炎症性肝病，是以肝内小及中等大小胆管损伤为主的器官特异性自身免疫病，本研究显示PBC病人体内存<WP=44>在高滴度的抗线粒抗体是诊断PBC的主要指标，与国内、外的报导相一致，而PBC外周血单个核细胞分泌的细胞因子水平则显示，PBC患者体内存在两种不同的T细胞亚群，与正常对照相比，PBC患者体内分泌不同细胞因子，也存在细胞因子比例失衡。TNF-α分泌增高激活T细胞导致IL-2、IFN-γ等细胞因子产生，并且始终参与免疫调节炎症过程。而高浓度的免疫球蛋白含量也证实，PBC患者体内存在细胞免疫异常的同时也存在明显的体液免疫异常，两者的共同作用是构成PBC免疫发病的基础。 综上所述自身免疫性疾病是活化T细胞及其细胞因子介导的不正常的免疫应答引起，其免疫系统的主要异常是依赖T细胞的B细胞功能亢进，产生大量自身抗体和免疫复合物，其发病中明显存在细胞因子比例失调，细胞因子谱偏移，但由于自身免疫病的发病机制比较复杂，对于各细胞因子在发病机制中的确切作用机制，尚无统一认识，普遍认为，SLE的发病与Th2占优势有关，导致B细胞过度克隆化，产生大量自身抗体，导致机体免疫系统损伤；但也有相反的观点，认为SLE是Th2占优势。本实验研究结论与第一种结论相符合。而PBC的发病过程中也存在细胞因子网络失衡，所以我们认为IL-4、IL-2、INF-γ、TNF-α可作为上述自身免疫性疾病病情活动的良好监测指标，并可作为疗效判断指标之一。同时测定自身抗体水平及其它免疫功能指标，对于探讨自身免疫病的发病机制，寻找有效方法调节患者体内上述细胞因子水平，从而调节体内Th1/Th2平衡状态，以达到治疗自身免疫病的目的。但自身免疫病的发病机制十分复杂，同一个病人可以同时存在多种细胞因子的异常，因而孤立的看待某一种细胞因子的异常，不能简单的认为降低的细胞因子即具有保护作用，升高的细胞因子具有致病作用，多种细胞因子相互作用可能更为重要。可能的机制是有遗传/或环境因素引起的一种或几种细胞因子的异常表达，引发细胞因子网络的失衡，从而最终导致发病。因此，对于自身免疫性疾病发病机制的进一步研究将成为免疫学领域的一个比较有前景的领域。更多还原

【Abstract】 The autoimmune disease is a kind of diseases that the organism autoimmune responses lose control and or overreacte, destroy self-tissue directly or indirectly, and arose pathological change of relevant organs or clinical symptoms, by intrinsic and extrinsic factors acting together. Systemic Lupus Erythematosus (SLE) and Primary Biliary Cirrhosis (PBC) are two different types of autoimmune diseases. Because of the disproportion of the T-cell subgroup, and Th1/Th2 cells disproportion in vivo, auto response T-cell proliferate, induce the B-cell activation, produce a great deal of autoantibody, form immune complex, injure the organism autoimmune system and lead to cellular immunity and humoral immunity dysfunction, and then cause the autoimmune diseases. This experiment determinate the autoantibody level in the serum and immunofluorescent patterns, circulating immunocomplex (CIC), serum C reactive protein (CRP), immunoglobulin (IgG, IgA, IgM) Complement (C3, C4) of 30 SLE patients and 30 PBC patients in our hospital and Dikuang Hospital, and the level of cytokine (IL-2, IL-4, TNF-α, IFN-γ) secreted by monocyte in the venous blood of part of the patients. And compared with the normal control group, it indicates that by the intrinsic and extrinsic factors act ing together, the organism autoimmune responses lose control, lead to the immunologic function injury, and then cause the autoimmune diseases. SLE is a kind of systemic immune disease, whose characteristic are polyclonal B cells activation and produced sorts of autoantibody. The serums of SLE patients contain several kinds of autoantibody in this experiment, thereinto the dsDNA antibody that has the obvious correlation with the activation of the disease, is the specific antibody. High concentration of CRP in serum indicates that the SLE patients immunologic function is the SLE patients disorder, and they <WP=46>are easily infected and have the correlation with the activation of the disease. The raise of immunoglobulin reported in literature doesn’t exist in the experiment. The decreases of the complement content confirm that the activation of the complement system and immunologic function injury does exist in SLE patients. The level of cytokine (IL-2, TNF-α, IFN-γ) secreted by monocyte in the venous blood are obviously lower than the normal control group, but the level of IL-4 is apparent higher than the control. Those research shows that there are many kinds of dysimmunity, disequilibrium of Th subgroup, Th1/Th2 dysfunction (Th2 hyperfunction and Th1 hypofunction), result in the cytokine meshwork dysfunction, B-cell over activation, produce sorts of autoantibody and immunologic dysfunction in SLE. PBC is a kind of chronic intrahepatic cholangitis caused by autoimmunity, whose characteristics are the injury of middle and small intrahepatic duct. It is an organ specific autoimmunity disease. The research indicates that the main diagnosis standard of PBC is the high concentration of anti-mitochondrial antibody in the serum of the patients, and it is the same with the reports from native or abroad. The level of cytokine (IL-2, IL-4, TNF-α, IFN-γ) secreted by monocyte in the venous blood of PBC patients shows that there are two different types of T-cell subgroup. And compared with the normal control group, there are different kinds of cytokines secreted in PBC, and the cytokines unbalance also exists. The increase of TNF-αactivate the T-cell to secrete the IL-2, IFN-γand other cytokines, and participate in the inflammatory process of immunoloregulation all the time. The high concentration of immunoglobulin also confirmed that there are the cellular dysimmunity and the humoral dysimmunity at the same time. Those two dysimmunity synchronously action becomes the basis of the PBC occurring. Above all, the autoimmunity disease is from the abnormal immune response caused by the activated T-cell and its cytokine. The main abnormity of immune <WP=47>system is the T depended B-cell hyperfunction, and secretes a great deal of autoantibody and immu更多还原