协同刺激分子B7对日本血吸虫感染小鼠肝虫卵肉芽肿病变的调控作用及其分子机制的研究

发布时间：2018-04-12 12:27

本文选题：日本血吸虫 + 虫卵肉芽肿　；参考：《苏州大学》2006年硕士论文

【摘要】： 本研究首先观察了日本血吸虫感染小鼠肝脏虫卵肉芽肿病变与Th1/Th2免疫偏移的相关性,并结合体内外实验进一步探讨用B7-1激发型mAb干预B7:CD28协同刺激信号途径介导感染小鼠Th1/Th2免疫偏移及其对肝虫卵肉芽肿病变的调节作用,并深入阐明其免疫病理的分子机制。结果进一步证明,日本血吸虫感染小鼠肝脏虫卵肉芽肿病变与Th1/Th2免疫偏移密切相关,由急性期Th1优势应答向慢性期Th2优势应答的转变介导着肉芽肿病变的慢性进展及纤维化的形成。B7-1激发型mAb体内外干预协同刺激信号均能显著上调感染小鼠脾淋巴细胞Th1细胞因子IFN-γ的表达水平(p0.05),对Th2细胞因子IL-4的表达则无明显影响。对反映Th1/Th2免疫偏移的IgG2a/IgG1及Th2分化指数分析表明,B7-1激发型mAb可介导感染小鼠的免疫应答向Th1方向偏移。同时,实验组感染小鼠肝脏虫卵肉芽肿的体积显著减小(P0.05)。免疫组化结果显示,实验组肝虫卵肉芽肿细胞B7-1分子的表达增强、B7-2分子的表达减弱。感染小鼠脾淋巴细胞培养上清NO的表达与IFN-γ的表达呈显著正相关,与IL-4的表达从感染6w后呈负相关,表明NO在肉芽肿病变过程中可能是一种与Th1/Th2细胞因子同样重要的免疫调节因子。研究结果表明,应用B7-1激发型mAb干预协同刺激信号途径可介导血吸虫特异性Th1/Th2免疫偏移调控虫卵肉芽肿病变,从而为探索虫卵肉芽肿病变新的免疫治疗途径提供理论依据,并可为血吸虫病疫苗的研制策略提供新的思路。
[Abstract]:This study first observed the correlation between liver egg granuloma and Th1/Th2 immune deviation of Schistosoma japonicum infection, combined with in vivo experiments to further explore the B7:CD28 with the B7-1 agonist mAb intervention of costimulatory signal pathway mediated infection of Th1/Th2 mice and their immune deviation on hepatic egg granuloma regulation, and further elucidate the molecular mechanism of immune pathology. The results further demonstrate that the liver of mice infected with Schistosoma japonicum egg granuloma with Th1/Th2 immune deviation is closely related by acute Th1 response and transition to chronic phase Th2 mediated response leads to the formation of.B7-1 advantage of agonist mAb in the progression of chronic granulomatous lesion and fibrosis of the intervention of costimulatory signal can increase expression level of gamma infection Th1 cell factor IFN- of mouse splenic lymphocytes (P0.05), on the expression of Th2 cytokines of IL-4 No obvious effect. To reflect the IgG2a/IgG1 and differentiation index Th1/Th2 immunodeviation Th2 analysis showed that B7-1 agonist mAb could mediate immune response of infected mice to Th1 shift. At the same time, the experimental group of mice infected with hepatic granuloma volume decreased significantly (P0.05). Immunohistochemistry showed that the expression of experimental group liver egg granuloma cells of the B7-1 molecule, the decreased expression of B7-2 molecule. The positive correlation between the expression of NO and IFN- in the culture supernatant of spleen lymphocytes of mice infected with gamma, and the expression of IL-4 from 6W infection was negatively correlated, suggest that NO may be an immune and Th1/Th2 cell factor as important regulatory factors in granuloma lesions in the process. The results show that the application of B7-1 agonist mAb intervention of costimulatory signal pathway can mediate the schistosome specific Th1/Th2 immune deviation regulation of egg granuloma, so as to explore the eggs It provides a theoretical basis for the new immunotherapy of granulomatosis and provides a new way of thinking for the development strategy of schistosomiasis vaccine.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R383

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