猴免疫缺陷病毒感染的免疫病理机制及中医药的干预作用

发布时间：2018-06-06 18:31

本文选题：猴免疫缺陷病毒 + 发病机制　；参考：《广州中医药大学》2005年博士论文

【摘要】：从感染HIV到发展为艾滋病的过程是长期的、缓慢的,在此期间,HIV与机体免疫系统之间的相互作用是持续的、复杂的。人们试图从多方面,以各种不同的原因来解释其病理机制,其中包括HIV对免疫细胞的直接杀伤作用。各类病原,包括真菌、病毒、细菌感染对HIV繁殖的激活作用,CD4与gpl20的相互作用,产生负信号,导致CD4~+细胞功能受损,由于HIV膜蛋白与MHCⅡ型抗原有同源序列,导致抗MHCⅡ型抗原的自身抗体,从而抑制了CD4~+细胞的免疫功能,基因型和抗基因型自身免疫反应的发生等。近年来,人们又提出细胞自溶,细胞因子从Th1类到Th2类的变化,以及呈递gp120抗原给已经活化的CD4~+细胞导致能量诱导并产生CD4~+细胞毒性细胞,引起自身免疫病变等。 HIV感染的发病机制存在多种假说,可能在HIV感染的病理变化,病程发展中都具有重要作用。但又似乎难以使人确信是导致最终发展为艾滋病的主要因素,纵观全局,以上各类假说可能都是一种表面现象,而根源所在可能应该归结于免疫活化。一经HIV感染,机体免疫系统从未能将其彻底清除。它的持续存在导致了免疫系统各类不同的效应细胞的慢性活化。这种持续不断的免疫活化在某些情况下,抑制了HIV的繁殖,阻止了HIV的扩散,产生有益作用。但在另外一些情况下,可引起免疫系统的过度活化,破坏了正常的免疫调节,导致免疫衰竭,对机体产生有害作用而促进疾病发展。从这一点上来看,各类免疫活化无论是发生在急性原发性感染时,或慢性潜伏性感染时,都具有双重作用。对机体既有保护作用,又有损害作用。例如,起初把HIV固定在淋巴组织中,对产生特异性的免疫反应是十分重要的,然而由于HIV可以直接感染免疫细胞,所以淋巴组织又成为最初建立HIV感染的一个良好的场所。和原发性特异性免疫反应相关的免疫活化是整个免疫反应中的一个正常环节,但活化了的免疫细胞又利于HIV的繁殖,从而引起HIV的进一步扩散。在原发性感染中产生的补体结合抗体有助于淋巴结生发中心内的树突状细胞捕获HIV,从而清除病毒,然而这种被捕获的病毒又可以造成新的感染。HIV感染引起细胞因子分泌的变化,有些细胞因子,如IFN-α能够抑制HIV的繁殖,增强免疫反应。而也有一些却促进了HIV的繁殖,或抑制机体的免疫反应。病毒的持续存在可以刺激机体不断产生保护性免疫反应。但有些病毒抗原,如go120却可能对CD4~+细胞发放负信号,导致“无反应”,诱发同种抗原反应或产生抗MHCⅡ型抗原的身体抗体,从而抑制T细胞功能.细胞自溶,在正常情况下可以限制活化的效应细胞。在HIV感染时,活化的效应细胞过多,出现大量细胞自溶,反而损害了免疫系统。HIV特异性的细胞毒性T细胞在抑制、消除HIV中有着重要的作用,但它也会耗竭抗原表达细胞,产生免疫病理反应。适当地诱导免疫活化,合理地控制免疫活化,尽量发挥免疫活化的益处,设法避免免疫活化的负作
[Abstract]:The process from infection with HIV to developing AIDS is long-term and slow. During this period, the interaction between HIV and the immune system is continuous and complex. People try to explain their pathological mechanism in many different ways, including the direct killing effect of HIV on the immune cells. All kinds of pathogens, including fungi, The interaction of HIV and gpl20, the interaction between CD4 and gpl20, causing negative signals, causing the function of CD4~+ cells to be damaged. Because the HIV membrane protein has the homologous sequence with the MHC type II antigen, it causes the autoantibodies against the MHC type II antigen and thus inhibits the immune function of CD4~+ cells, the genotype and the anti genotypic autoimmune reaction. In recent years, people have proposed cell autolysis, changes in cytokines from class Th1 to Th2, and the presentation of gp120 antigen to the activated CD4~+ cells resulting in energy induction and production of CD4~+ cytotoxic cells, causing autoimmune diseases.
There are many hypotheses about the pathogenesis of HIV infection, which may play an important role in the pathological changes of HIV infection and the development of the course of disease. However, it seems that it is difficult to make sure that it is the main factor leading to the final development of AIDS. All the hypotheses may be a surface phenomenon, and the root cause may be attributed to immunity. Activation. As soon as HIV infection, the body's immune system has never been completely removed. Its persistence leads to chronic activation of various effector cells in the immune system. This continuous immune activation, in some cases, inhibits the propagation of HIV, prevents the proliferation of HIV, and produces beneficial effects. In other cases, The excessive activation of the immune system, which destroys the normal immune regulation, causes the immune failure and causes the harmful effects of the body to promote the development of the disease. From this point of view, all kinds of immune activation have double effects both in acute primary infection, or in chronic latent infection. It is damaging. For example, it is important to fix HIV in the lymphoid tissue at first, which is very important to produce a specific immune response. However, because HIV can infect immune cells directly, the lymphoid tissue is a good place for the initial establishment of HIV infection. A normal link in a pestilence reaction, but the activated immune cells are also beneficial to the proliferation of HIV, which causes further diffusion of HIV. The complement binding antibody produced in the primary infection helps to capture the HIV in the dendritic cells in the lymph node germinal center, thus eliminating the virus, but this captured virus can cause a new sense of the virus. .HIV infection causes changes in cytokine secretion, and some cytokines, such as IFN- alpha, can inhibit the reproduction of HIV and enhance the immune response. Some also promote the reproduction of the HIV or inhibit the immune response of the body. The persistent presence of the virus can stimulate the body to produce a protective immune response. However, some viral antigens, such as go120, can be used. Negative signals can be distributed to CD4~+ cells, causing "no reaction", inducing the homoantigen reaction or producing anti MHC type II antigen of the body antibody, which inhibits the function of T cells. Cell autolysis can restrict activated effector cells under normal conditions. In HIV infection, the activated effector cells are too much, and a large number of cells are autolysis, but are impaired instead. .HIV specific cytotoxic T cells in the immune system have an important role in inhibiting and eliminating HIV, but it also depleted the antigen expressing cells and produced immune pathological reactions. Appropriate induction of immune activation, rational control of immune activation, the benefits of immune activation as far as possible, and the avoidance of negative activities of immune activation.
【学位授予单位】：广州中医药大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392;R259

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