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首页> 外文会议>Advances in biomedical research >IMMUNOPROPHYLACTIC MECHANISMS OF GLYCOLIPID ANTIGENS IN TUBERCULOSIS
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IMMUNOPROPHYLACTIC MECHANISMS OF GLYCOLIPID ANTIGENS IN TUBERCULOSIS

机译：结核病中糖脂抗原的免疫促生机制

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Mycobacterium tuberculosis is one of the most dangerous human pathogens evolved on the Planet that poses big challenge to the scientists working on diagnostics and therapeutics. There is an urgent requirement for the development of a novel candidate as an immunoprophylactic agent (vaccine). The complete genome sequencing of M. tuberculosis H37 Rv had paved way for the identification of candidate antigens of prophylactic significance. Numerous proteins especially membrane proteins acting as immunogens or subunit vaccines are profiled and investigated for immunoprophylactic activity. The protein of 71 kDa, which elicits the response of both B cell/T cell has been used for the development of candidate vaccine. However the use ofproteinaceious antigens in immunoprophylaxis is not encouraging for various reasons. The lipid based immunogenic antigens find to be more promising in this regard, since lipids escape the coventional antigen processing and are routed through CD1 system by a different pathway. The lipid antigens are endocytosed through a pathway involving protease resistant proteins such as saposin. Saposin molecules help CD1 molecules to present the antigen to the T Cell and NKT cells. The NKT cells play a larger regulatory role and have immunomodulatory properties and hence NKT cells are attractive targets for the development of immunotherapies. Another advantage of lipid Ag induced immune response is its specificity, which is attributed by 8,y region of the variable chain of the TCR. This region of TCR are not diverse in it function. Hence the rate of elimination of mycobacterium will be rapid if the lipid Ag is challenged. The other advantages of priming with lipid moieties include, i. rate of mutation of CD1 molecules is not rapid, limited polymorphism of CD1 etc. The use ofliposome technology in enhancing the immune response is under active invesitgation. Mycobacterial mannophosphoinositides (PIMs) encapsulated in liposomes made of egg phosphatidylcholine (EPC) and cholesterol (CH) (2:1.5 molar ratio) were able to induce humoral and delayed type hypersensitivity (DTH, foot-pad swelling reaction) responses in mice without the help of any carrier protein. Animals immunized with this liposome glycophospholipid antigen demonstrated enhanced percent survival on intravenous challenge with virulent M. tuberculosis. The paper deals with the immunoprophylactic studies carried out with M. tuberculosis derived lipid based antigens.
机译：结核分枝杆菌是地球上进化的最危险的人类病原体之一，这给从事诊断和治疗工作的科学家提出了巨大的挑战。迫切需要开发一种新型候选物作为免疫预防剂（疫苗）。结核分枝杆菌H37 Rv的完整基因组测序为鉴定具有预防意义的候选抗原铺平了道路。对用作免疫原或亚单位疫苗的多种蛋白质，特别是膜蛋白质进行了分析，并研究了其免疫预防活性。引起B细胞/ T细胞应答的71kDa蛋白已被用于候选疫苗的开发。但是，出于各种原因，不鼓励在免疫预防中使用蛋白质抗原。在这方面，基于脂质的免疫原性抗原被认为更有前景，因为脂质逃脱了常规抗原的加工，并通过不同的途径通过CD1系统。脂质抗原通过涉及蛋白酶抗性蛋白如鞘脂蛋白酶的途径被内吞。 Saposin分子帮助CD1分子将抗原呈递给T细胞和NKT细胞。 NKT细胞发挥更大的调节作用，并具有免疫调节特性，因此NKT细胞是免疫疗法发展的有吸引力的靶标。脂质Ag诱导的免疫应答的另一个优点是其特异性，这归因于TCR可变链的8，y区。 TCR的这一区域在功能上并不多样化。因此，如果挑战脂质Ag，分枝杆菌的消除速度将很快。用脂质部分引发的其他优点包括，即。 CD1分子的突变率不是很快，CD1的多态性有限等。在积极研究中使用脂质体技术增强免疫反应。卵磷脂磷脂酰胆碱（EPC）和胆固醇（CH）（2：1.5摩尔比）制成的脂质体中包埋的分枝杆菌甘露糖苷（PIM）能够在小鼠体内诱发体液和迟发型超敏反应（DTH，足垫肿胀反应）。任何载体蛋白的帮助。用这种脂质体糖磷脂抗原免疫的动物表现出在毒性结核分枝杆菌的静脉内攻击后存活百分比提高。该论文涉及对结核分枝杆菌衍生的基于脂质的抗原进行的免疫预防研究。

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