【作者】 黄秀艳；

【导师】 曾耀英；

【作者基本信息】 暨南大学 ， 免疫学， 2006， 硕士

【摘要】 本研究旨在探讨肠免疫系统有别于系统免疫系统的特征，在此基础上探讨肠相关淋巴组织中淋巴细胞对HIV感染的容许性和HIV复制的支持性，最后，探讨AT-2灭活HIV病毒颗粒在HIV感染时所引起的免疫过度活化的分子基础，为艾滋病以肠道为靶向的新治疗策略的制定奠定免疫学基础。也就是说，通过此研究初步验证我们所提出的“HIV感染肠道免疫系统过度活化论”工作假说。我们的假说认为：在正常情况下，肠道免疫系统处于生理性活化状态和生理性低反应性状态，其生理性活化状态为HIV感染提供了大量的易感细胞。而在HIV感染时，由于危险信号的释放，病毒子模拟APc的作用，调节性T细胞优先被删除等原因导致生理性低反应性状态被打破，而出现免疫过度活化，从而产生更多的HIV易感细胞，通过直接感染以及活化诱导细胞凋亡，使肠道T细胞在短期内大量丢失，从而导致免疫缺陷。为此，我们进行了三个方面的研究：小鼠肠粘膜免疫系统特点分析；人肠道HIV感染容许性和HIV复制支持性分析；HIV感染免疫过度活化机理体外实验分析。 论文的第一部分，通过对小鼠派氏集合淋巴结(PPs)、肠系膜淋巴结(MLNs)和腹股沟淋巴结(ILNs)的比较性研究，以分析小鼠肠道免疫系统的特点。以往的研究表明，由于肠道是机体营养吸收和共生菌繁殖的主要场所，精确区分入侵病原微生物和无害的食物和共生菌抗原成为肠粘膜免疫系统的结构和功能进化的原动力。在功能上，肠道免疫系统能十分清楚地区分哪些是有害的抗原(例如入侵微生物)，哪些是无害的抗原(例如食物抗原和肠道共生菌)，以便作出合适的免疫应答，以清除有害的抗原而对无害的抗原形成耐受，以保护机体免受病理性损伤；在结构上，分为免疫应答“诱导”部位(“inductive”sites)和免疫应答“效应者”部位(“effector”sites)，前者与免疫应答的启动和免疫耐受的诱导有关，后者参与实施免疫应答的效应者机制。本部分我们采取了以下的研究方法：无菌分离小鼠PPs、更多还原

【Abstract】 The aim of this study is to investigate characteristics of the intestinal mucosal immune system which are different from those of systemic immune system. On the basis of this study, further investigation will be made into the permissiveness of HIV infection and the supportiveness of HIV replication of lymphocytes within gut-associated lymphoid tissues (GALT). Finally, analysis will be undertaken on the molecular basis of hyper-activation of immune system caused by HIV infection through AT-2 inactivated HIV particles. The findings of the studies will lay the foundations of establishing new strategy for HIV therapy targeting to intestine. In other words, we prove our working hypothesis related to immune hyper-activation within intestinal mucose during HIV infection by the studies. The hypothesis postulates that intestinal immune system is in the state of physiological activation and physiological hypo-responsiveness in health; whereas it is that physiological hyper-activation provides large number of susceptible cells for HIV infection. In the case of HIV infection, transposition occurs from hypo-responsiveness to hyper-activation due to release of danger signals, mimicry of APC by HIV particles, and preferential depletion of regulatory T cells. As a result of hyper-activation, more and more cells are susceptible to HIV infection. And then plenty of CD4~+ T lymphocytes are deleted through infection and activation induced cell death (AICD). Therefore, our study is divided into three parts: characterizations of murine intestinal immune system; the permissiveness of HIV infection and the supportiveness of HIV replication of lymphocytes within human gut-associated lymphoid tissues; analysis of molecular basis of hyper-activation of immune system caused by HIV infection through AT-2 inactivated HIV particles.更多还原