CpG诱导Th1型免疫应答及其对血吸虫肝虫卵肉芽肿病变调节作用的研究

发布时间：2018-05-03 23:09

  本文选题：日本血吸虫 + 虫卵肉芽肿　； 参考：《苏州大学》2005年硕士论文

【摘要】：近年来研究表明,血吸虫卵肉芽肿病变主要是由虫卵可溶性抗原诱导的以Th2型免疫优势应答介导的,以嗜酸性粒细胞等多种炎症细胞浸润为主的免疫病理反应。控制血吸虫卵肉芽肿病变对防止晚期血吸虫病肝纤维化的发生发展具有重要作用。利用Th1和Th2亚群的相互拮抗作用来调节虫卵肉芽肿反应,可改善纤维化病变。含非甲基化CpG序列的寡脱氧核苷酸(免疫刺激序列),经体外和大量的动物实验证实它能激活哺乳动物的天然免疫系统,刺激巨噬细胞、单核细胞等产生IFN-γ、IL-12等细胞因子,激发强烈的Th1型免疫应答反应,或调节免疫应答向Th1型转换,抑制Th2型免疫应答。小鼠动物实验表明CpG亦能够调节曼氏血吸虫虫卵诱导的Th2型免疫应答,减轻虫卵肉芽肿反应。本研究通过观察CpG在体内、外对Th1/Th2免疫偏移的调控作用,探讨其对日本血吸虫卵肉芽肿及纤维化发生、发展的影响。结果表明:在体外实验中,CpG可协同SEA或ConA显著上调体外培养小鼠脾淋巴细胞Th1型细胞因子IFN-γ的表达水平,下调Th2型细胞因子IL-4的表达水平,特别是促进IFN-γ的表达作用强烈,并结合Th2分化指数进一步说明CpG主要介导Th1型免疫应答;在体内实验中,CpG免疫鼠产生肝脏虫卵肉芽肿的密度与生理盐水对照组相比较低,单卵肉芽肿形成的肉芽肿体积与生理盐水对照组有较明显差异。血清抗体IgG及抗体亚类IgG_1、IgG_(2a)检测表明:6、8w时CpG组血清抗体IgG较N-CpG组以及NS对照组水平低,6w时CpG组IgG_(2a)/IgG_1的比值较对照组高,提示CpG主要诱导Th1型免疫应答。本研究表明CpG作为一个新型的免疫调节剂及其作为潜在的疫苗佐剂具有重要的理论和应用价值,研究结果为探索控制日本血吸虫虫卵肉芽肿病变的新途径提供了实验依据。
[Abstract]:Recent studies have shown that schistosomiasis oocyte granulomatosis is mainly induced by egg soluble antigen mediated by Th2 immune dominant response and mainly by eosinophilic granulocyte infiltration. The control of schistosomiasis oocyte granuloma plays an important role in preventing the occurrence and development of liver fibrosis in advanced schistosomiasis. Using the antagonism of Th1 and Th2 subsets to regulate the egg granuloma reaction can improve the fibrosis lesion. Oligodeoxynucleotides (oligodeoxynucleotides) containing non-methylated CpG sequences (immunostimulatory sequences) have been shown to activate mammalian innate immune system, stimulate macrophages and monocytes to produce cytokines such as IFN- 纬 IL-12. To stimulate a strong Th1 type immune response, or to regulate the transition from immune response to Th1 type, and to inhibit Th2 type immune response. Animal experiments in mice showed that CpG could also modulate the Th2 type immune response induced by Schistosoma mansoni eggs and alleviate the egg granuloma response. The aim of this study was to investigate the effects of CpG on the development and development of schistosomiasis japonicum oocyte granuloma and fibrosis by observing the effect of CpG on Th1/Th2 immune shift in vivo and in vitro. The results showed that CpG could significantly upregulate the expression of Th1 type cytokine IFN- 纬 and down-regulate the expression of Th2 type cytokine IL-4, especially the expression of IFN- 纬, in combination with SEA or ConA. Combined with the differentiation index of Th2, CpG mainly mediated the Th1 type immune response, and the density of liver egg granuloma in CpG immunized mice was lower than that in normal saline control group. The volume of granuloma formed by single egg granuloma was significantly different from that of normal saline control group. The detection of serum antibody IgG and antibody subclass IgG tip2a showed that the ratio of serum antibody IgG in CpG group was higher than that in N-CpG group and CpG group at 6w / 6w, suggesting that CpG mainly induces Th1 type immune response. This study shows that CpG as a new immunomodulator and as a potential vaccine adjuvant has important theoretical and practical value. The results provide experimental basis for exploring a new approach to control schistosome egg granuloma in Schistosoma japonicum.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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