疟原虫代谢分泌物在增强蛋白抗原免疫保护力中的作用

发布时间：2018-07-15 17:37

【摘要】：疟疾是由疟原虫引起的,是最严重的传染病之一,每年导致100万人死亡,目前109个国家正遭受疟疾感染的危险。疟疾是由按蚊传播,随着叮咬人体而将疟原虫注入人体血液循环中,它可以导致低血糖症、发热、贫血等临床症状。目前有四种人疟和四种鼠疟,其中夏氏疟原虫是研究恶性疟原虫最佳的小鼠模型。目前研发的用于抵抗疟疾的疫苗种类有很多,亚单位疫苗是研究最多的。它可以引起很强的体液免疫,但细胞免疫较弱,不能引起持久的免疫保护力。亚单位疫苗需要佐剂的辅助来增强免疫反应。MSP1是最重要的亚单位候选疫苗,可以引起一定的保护力。它经一系列切割最后只剩C端19kDa经GPI连接在虫表面并进入红细胞中。有前人报道发现从疟原虫体外培养的上清中有某些物质可以与疟疾感染的病人的阳性血清发生作用。因此本实验我们想研究MSP1和疟原虫培养上清共同免疫的效果。首先利用大肠杆菌表达系统获得夏氏疟原虫AS株MSP1蛋白C端11kDa;其次体外短期培养夏氏疟原虫获得代谢分泌物(ES)。将MSP1与代谢分泌物共同免疫小鼠,检测感染率、ELISA检测抗体滴度;免疫小鼠的脾细胞培养,研究细胞因子的分泌和细胞激活状态。实验发现:(a)MSP1以ES为佐剂免疫可以有效抑制血虫水平;产生较高的抗体水平,主要有IgG1、IgG2c和IgG2b;(b)激活了树突状细胞,使CD40、CD86分子表达升高,MHC-II表达下降;(c)激活了CD4+T细胞,使其表面分子CD62L表达下降;(d)诱导淋巴细胞的增殖,产生较高的IFN-γ、IL-12和IL-10。本研究第一次将代谢分泌物作为新型佐剂。我们的研究结果揭示了抗疟疾免疫诱导的复杂机制,并可能对疟疾疫苗的研发具有重要意义。
[Abstract]:Malaria is caused by malaria parasites, one of the most serious infectious diseases, which causes 1 million people to die each year, and 109 countries are currently in danger of malaria infection. Malaria is transmitted by Anopheles. It can lead to clinical symptoms such as hypoglycemia, fever, anemia as the bite of the human body inject the Plasmodium into the blood circulation of the human body. There are four kinds of symptoms at present. Plasmodium falciparum is the best mouse model for studying Plasmodium falciparum and four kinds of rat malaria.
There are many kinds of vaccines used to resist malaria at present. Subunit vaccines are the most studied. It can cause very strong humoral immunity, but the cell immunity is weak and can not cause persistent immune protection. Subunit vaccine needs adjuvant to enhance immune response.MSP1 is the most important subunit candidate vaccine and can be caused by the subunit vaccine. Certain protective power. It has been cut through a series of C end 19kDa and connected to the insect's surface and into the red cells by GPI. Some of the previous reports have found that some of the substances in the supernatant from the Plasmodium in vitro may be able to play a role in the positive sera of the patients infected with malaria.
Therefore, we want to study the effect of the co immunization of MSP1 and Plasmodium culture supernatant. First, we use the Escherichia coli expression system to obtain the C terminal 11kDa of the Plasmodium chariera AS strain MSP1 protein; secondly, to obtain the metabolic secretions (ES) in the short term culture of Plasmodium charium (ES). The infection rate and ELISA detection are detected by the co immunization of MSP1 and metabolic secretory substances in mice. The antibody titer, immunized mice spleen cell culture, study the secretion of cytokine and cell activation state. The experiment showed that (a) MSP1 with ES as adjuvant immunization could effectively inhibit the blood worm level; high antibody level, mainly IgG1, IgG2c and IgG2b; (b) activated dendritic cells, the expression of CD40, CD86 molecules increased, MHC-II expression decreased; C) activation of CD4+T cells, reducing the expression of CD62L on its surface molecules; (d) inducing lymphocyte proliferation, producing higher IFN- gamma, IL-12 and IL-10. as a new adjuvant for the first time. Our results reveal the complex mechanism of anti malaria immunity induction and may be of great significance to the development of malaria vaccine.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392

【相似文献】