天然免疫分子人可溶性CD14、TLR4与肾脏移植免疫关系的临床研究

发布时间：2018-03-21 02:17

本文选题：可溶性CD14　切入点：Toll样受体4　出处：《第一军医大学》2006年博士论文　论文类型：学位论文

【摘要】：在移植免疫中，T淋巴细胞在双信号刺激下才能被激活和发生增殖，从而启动由淋巴细胞、细胞因子、补体等参予的错综复杂的移植排斥反应。如果抗原提呈细胞(antigen present cell，APC)只提供MHC-抗原肽复合物而不提供CD80、CD86等共刺激信号，将使淋巴细胞无能，诱导免疫耐受。目前，国内、外关于移植免疫的研究主要集中在以T／B淋巴细胞及其下游细胞因子为中心的免疫过程，由于T／B淋巴细胞活化后移植免疫网络的复杂性，以该免疫网络某一个环节为靶点的治疗措施往往事倍功半。显然，针对淋巴细胞活化的上游信号传导者APC的研究将具有显而易见的优势。APC表面共刺激分子的表达是决定T细胞异基因免疫反应性的关键因素。APC表面CD80、CD86等共刺激分子的下调可以使APC转变为致耐受性细胞，使T细胞失去发生异基因反应的能力。但问题是，CD80、CD86的表达是由谁调控的?如何调控的?1997年，人类天然免疫模式识别受体TOLL样受体(Toll like receptor，TLR)的发现使得以APC为主要对象的移植免疫研究成为可能。早期关于TLR的研究主要集中在抗感染免疫方面，TLR是天然免疫用以识别各种致病微生物共有结构的“工具”，TLR与各种致病微生物共有的保守结构也即病原相关分子模式结合后，激活相应的信号传导通路，促进单核／巨噬细胞、树突状细胞等抗原提呈细胞的成熟与活化，上调CD80、CD86等共刺激分子的表达，启动天然免疫，消灭入侵的病原体。随着研究的进一步深入，发现TLR还在移植免疫、动脉粥样硬化形成中起重要作用。其中，TLR4与移植免疫关系的研究显示出极具诱人的前景。在可溶性CD14(soluble CD14，sCD14)帮助下，APC上的TLR4与革兰氏阴性菌内毒素脂多糖LPS结合并活化，通过一系列信号传导，，引起NF-κB活化，
[Abstract]:In transplant immunity, T lymphocytes can only be activated and proliferated under the stimulation of double signals, and thus activated by lymphocytes, cytokines, If antigen presenting cell antigen present cell (APC) provides only MHC-antigen peptide complex but not costimulatory signal such as CD80 or CD86, it will cause lymphocyte anergy and induce immune tolerance. At present, domestic and foreign researches on transplantation immunity mainly focus on the immune process centered on T / B lymphocytes and their downstream cytokines. Because of the complexity of the transplantation immune network after T / B lymphocytes are activated, Therapeutic measures targeted at one link of the immune network are often half-effective. Obviously, The study on upstream signal transducers of lymphocyte activation will have obvious advantages. The expression of costimulatory molecules on APC surface is the key factor to determine the allogeneic immunoreactivity of T cells. CD80 CD86 and other costimulatory molecules on the surface of APC are the key factors to determine the allogenic immunoreactivity of T cells. The down-regulation of APC can transform APC into tolerant cells. Make T cells lose the ability to produce allogenic reactions. But the question is, who regulates the expression of CD80? How? 1997, The discovery of human innate immune pattern recognition receptor TOLL-like receptor Toll like receptor makes it possible to study transplantation immunity with APC as the main object. Early studies on TLR mainly focused on anti-infection immunity. In order to identify the common structures of various pathogenic microorganisms, the TLR binds to the conserved structure shared by various pathogenic microorganisms, that is, pathogen-related molecular patterns. Activating the corresponding signal transduction pathway, promoting the maturation and activation of antigen-presenting cells such as monocytes / macrophages and dendritic cells, upregulating the expression of costimulatory molecules such as CD80, CD86, and initiating innate immunity. With the further development of research, it is found that TLR still plays an important role in the pathogenesis of atherosclerosis, and the relationship between TLR4 and transplantation immunity is very attractive. Under the help of soluble CD14(soluble CD14s CD14, TLR4 on APC binds and activates lipopolysaccharide (LPS) from gram-negative bacteria, which activates NF- 魏 B through a series of signal transduction.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R699.2;R392.4

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