【作者】 田芳；

【导师】 夏超明；

【作者基本信息】 苏州大学 ， 病原生物学， 2004， 硕士

【摘要】 研究表明血吸虫虫卵肉芽肿病变与Th1／Th2免疫偏移密切相关，提示调控Th1／Th2免疫偏移是控制肉芽肿病变的有效途径。T细胞活化需要双信号，第二信号即协同刺激信号对Th细胞极化及细胞因子分泌起重要的调节作用。B7和CD40是T细胞活化的两种主要的协同刺激分子，本研究通过观察干预协同刺激信号对Th1／Th2免疫偏移的调控作用，探讨其对血吸虫虫卵肉芽肿发生、发展的影响。结果表明抗B7-1(CD80)mAb和抗B7-2(CD86)mAb能部分抑制IFN-γ的产生，但其作用均不明显，而对IL-4的抑制作用较强(P＜0.01)，特别是抗B7-2mAb能显著抑制IL-4的表达，抗CD40mAb和抗CD40LmAb对IL-4也有显著抑制作用(P＜0.01)，并结合NO水平检测进一步证明上述机制。同时应用免疫组化分析不同感染时期虫卵肉芽肿细胞上B7-1、B7-2、CD40、CD40L的表达强度与虫卵肉芽肿病变的相关性。进一步探讨协同刺激分子对日本血吸虫特异性Th1／Th2免疫偏移的影响及其免疫病理机制。实验结果显示，4种协同刺激分子均参与虫卵肉芽肿的形成，尤其是B7-2和CD40分子的作用更为显著。其机制可能为该两种协同刺激分子介导Th2优势应答所致。研究结果深入阐明了血吸虫病免疫病理的分子机制，对寻找控制血吸虫虫卵肉芽肿病变的新途径，防止晚期血吸虫病的发生、发展具有重要的理论意义和应用价值。更多还原

【Abstract】 Recent studies showed that regulating Th1/Th2 immunodeviation is a effective method to control granulomatous formation. The activation of T cells required two signals. The second signal is co-stimulatory which can regulates Th cell polarization and cytokine secretion. B7-1/2:CD28 and CD40:CD40L are two kinds of important co-stimulatory signals of T cell activation. In this paper, through observing the regulating effects on Thl/Th2 immunodeviation to interfere with the two kinds of co-stimulatory signals, we probed the effect on eggs granulomatous formation. The results showed that the Anti-B7-lmAb and Anti-B7-2mAb could not significantly inhibit the IFN- Y expression (P>0.01). But they could significantly inhibit the expression of IL-4 (P<0. 01), and the effect of Anti-B7-2mAb is stronger than that of Anti-B7-lmAb. Anti-CD40mAb and Anti-CD40LmAb could also significantly inhibit the levels of IL-4 but not that of IFN-Y . The measure of NO levels further demonstrated above the mechanism. The same time we analyzed the correlation of the expression of B7-1/2 and CD40/CD40L on liver egg granulomatous cells and the granuloma during different infection phases. We further probed the effects of co-stimulatory molecules on the specific Thl/Th2 immunodeviation of Schistosoma japanicum and its immunopathologic mechanism. The results show that the four co-stimulatory molecules anticipate the egg granuloma formation. Especially the effect of B7-2 and CD40 molecules are more significant. Its mechanism is probably the two kinds of molecules mediating Th2 predominant reaction. These results have important theoretic and practical value for finding the new pathway to control eggs granuloma and preventing advanced schistosomiasis.更多还原