卡介苗embC基因敲除株的构建和免疫调节功能研究

发布时间：2018-04-13 04:17

本文选题：BCG + embC基因　；参考：《四川大学》2006年硕士论文

【摘要】：近年来，结核的发病率逐年上升，在全球范围对人类健康造成危害。通过BCG接种免疫是预防结核的一个主要的可行性手段，具有可靠方便和安全的特点。但BCG的免疫性不能达到完全控制结核的效果，有研究表明，不同地区、不同年龄的人群接种了BCG后的有效率在0％到80％，因此提高BCG的免疫性成为迫切的需要。脂阿拉伯甘露聚糖(1ipoarabinamannan，LAM)被认为是结核分支杆菌的毒力因子之一，通过与巨噬细胞上的甘露糖受体作用而调节宿主的免疫反应，它以复杂的脂多糖形式限制性的分布在分支杆菌类群的细胞膜上。纯化后的ManLAM参与了结核杆菌体内感染时抑制某些细胞因子分泌的作用如IL-12、TNF-α、IL-8，使诱发的巨噬细胞凋亡减少并调节树突状细胞的抗原呈递过程，对结核杆菌的毒力和免疫逃避作用可能有大的影响。而通过分离纯化得到了BCG细胞壁上的ManLAM，在体外攻击巨噬细胞实验中，发现抑制了巨噬细胞分泌的IL-8和TNF-α。对M．tuberculosis，M．leprae，M．bovis BCG，M．kansassi，，M．avium，M．smegmatis以及M．chelonae等分支杆菌胞壁的LAM结构进行分析，它包含了三个结构区，两个同聚多糖D-甘露糖苷和D-阿拉伯糖苷连接在磷脂酰肌醇(PI)上，并通过PI锚定于胞膜上。不同的分支杆菌中通过区分识别结合到D-阿拉伯糖末端的不同的糖苷而把LAM主要分为三类，主
[Abstract]:In recent years, the incidence of tuberculosis has been increasing year by year, which is harmful to human health worldwide.Immunization through BCG is a main feasible method to prevent tuberculosis, which has the characteristics of reliability, convenience and safety.However, the immunogenicity of BCG can not achieve the effect of complete control of tuberculosis. Some studies have shown that the effective rate of BCG inoculated in different regions and different ages is between 0% and 80%, so it is urgent to improve the immunity of BCG.Lipoarabinamannan (Lam) is considered to be one of the virulence factors of Mycobacterium tuberculosis, which regulates the host's immune response by acting with mannose receptors on macrophages.It is restricted in the form of complex lipopolysaccharide to the cell membrane of mycobacteria.Purified ManLAM is involved in inhibiting the secretion of some cytokines by Mycobacterium tuberculosis in vivo, such as IL-12, TNF- 伪, IL-8, which reduces the apoptosis of macrophages and regulates the antigen presentation of dendritic cells.It may have a great effect on the virulence and immune evasion of Mycobacterium tuberculosis.ManLAM on the cell wall of BCG was isolated and purified, and IL-8 and TNF- 伪, which inhibited the secretion of macrophages, were found in the experiment of attacking macrophages in vitro.The LAM structure of M. tuberculosisus M. bovis BCGK, M. aviumus M. smegmatis and M. M.chelonae were analyzed. It consists of three structural regions, two isopolysaccharide D-mannoside and D-arabinoside linked to phosphatidylinositol (Pi), and anchored on the cell membrane by Pi.In different mycobacteria, LAM is divided into three types by distinguishing the different glycosides that bind to the end of D-arabinose.
【学位授予单位】：四川大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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