日本血吸虫成虫与虫卵抗原刺激小鼠免疫细胞增殖、分化与免疫抑制功能的研究

发布时间：2018-02-22 03:47

  本文关键词： 日本血吸虫 成虫抗原 虫卵抗原 免疫效应 免疫调控　出处：《南京医科大学》2010年硕士论文　论文类型：学位论文

【摘要】：在我国,血吸虫病仍然是当今主要公共卫生问题之一。血吸虫病是一种典型的慢性感染性、免疫性疾病,在血吸虫感染过程的不同时期机体免疫系统针对血吸虫各发育阶段的不同抗原产生不同的优势免疫应答。成虫抗原(SWA)、虫卵抗原(SEA)是血吸虫感染过程中最主要的两种抗原成分。自然感染过程中,这两类抗原共同存在、作用相互叠加相互影响,结果更为复杂。因此,为研究这两种抗原在血吸虫感染后的宿主的免疫效应和免疫负调控中的异同作用,我们首先通过体内外实验观测SWA和SEA对小鼠脾细胞、CD4~+T淋巴细胞的增殖、分化等免疫效应发生发展中的重要因素的不同影响;其次,通过体内外实验观测SWA和SEA刺激小鼠CD4~+T淋巴细胞凋亡和诱导CD4~+CD25~+Treg细胞并产生免疫抑制因子等免疫负调控中的重要因素的不同作用。结果发现:与SWA相比,SEA更易刺激脾细胞增殖(p0.01),且SEA也更易刺激CD4~+T淋巴细胞增殖(p0.05)。同时,流式细胞术结果检测显示,与SWA相比,SEA能更好地刺激脾细胞及其中的CD4~+T淋巴细胞亚群产生IL-4和IL-17(p0.05),但SEA刺激产生IFN-γ的能力显著较SWA低(p0.05)。凋亡检测结果显示,SWA、SEA均能刺激CD4~+T淋巴细胞的凋亡,但二者差异无统计学意义(p0.05);进一步观测两种抗原诱导CD4~+CD25~+FOXP3~+Treg细胞的比例变化时发现,SEA能比SWA诱导更高比例的CD4~+CD25~+FOXP3~+Treg细胞(p0.05),且SEA比SWA刺激CD4~+CD25~+Treg细胞免疫抑制功能的能力可能也更强(p0.05);SWA、SEA免疫小鼠后,SEA显示其刺激CD4~+CD25~+Treg细胞产生IL-10、TGF-β的能力更高(p0.001)。上述结果提示,SEA比SWA更易刺激脾细胞和CD4~+T淋巴细胞的增殖、更能优势诱导Th2和Th17细胞的分化以发挥免疫效应作用、并能更好地活化诱导CD4~+CD25~+Treg细胞发挥免疫抑制作用。但是,SWA比SEA更能优势诱导Th1细胞的分化。 总之,我们的研究提示SEA较SWA更易诱导宿主产生免疫反应,从而通过刺激免疫效应与免疫调节(免疫抑制)两方面在血吸虫病发展为慢性感染性疾病中发挥重要作用,我们的研究结果为血吸虫病的防控(疫苗研究)和治疗(免疫病理控制)提供了理论依据,同时,也为建立以血吸虫及其SWA、SEA抗原为工具的免疫研究模型、并在其它免疫相关疾病领域中的广泛应用提供了更深入的理论依据。
[Abstract]:Schistosomiasis is still one of the major public health problems in China. Schistosomiasis is a typical chronic infectious, immune disease. In different stages of schistosomiasis infection, the immune system produces different dominant immune responses to different antigens of Schistosoma japonicum at different stages of development. The adult worm antigen SWAA (egg antigen SEAA) is the most important one in the process of schistosomiasis infection. Antigenic components. In the process of natural infection, These two kinds of antigens exist together and interact with each other, and the results are more complicated. Therefore, in order to study the immune effects and negative immune regulation of the host infected by Schistosoma japonicum, At first, we observed the different effects of SWA and SEA on the proliferation and differentiation of CD4T lymphocytes in mouse splenocytes by in vitro and in vivo experiments. The effects of SWA and SEA on the apoptosis of CD4T lymphocytes and the production of immunosuppressive factors such as CD4- CD25- Treg cells were observed in vivo and in vitro. The results showed that sea was more important than SWA. It is easy to stimulate the proliferation of spleen cells, and SEA is more likely to stimulate the proliferation of CD4 ~ T lymphocytes. The results of flow cytometry showed that, Compared with SWA, sea could stimulate spleen cells and CD4 ~ T lymphocyte subsets to produce IL-4 and IL-17 p0.05, but the ability of SEA to produce IFN- 纬 was significantly lower than that of SWA. Apoptosis assay showed that SWASEA could stimulate apoptosis of CD4T lymphocytes. However, there was no significant difference between the two antigen-induced CD4 ~ CD25 ~ FOXP3 ~ Treg cells, and it was found that sea could induce a higher proportion of CD4 ~ CD25 ~ FOXP3- Treg cells than SWA, and that SEA stimulated CD4 ~ CD25 ~ Treg cell immunosuppression more than SWA. The functional ability of SWA-sea immunized mice may also be stronger. After immunizing mice, sea showed a higher ability to stimulate the production of IL-10 TGF- 尾 by CD4 ~ CD25- Treg cells. These results suggest that sea is more likely than SWA to stimulate the proliferation of spleen cells and CD4T lymphocytes. SWA could induce the differentiation of Th2 and Th17 cells in order to play an immune effect, and could activate and induce CD4 ~ CD25 ~ Treg cells to play an immunosuppressive effect, but SWA could induce the differentiation of Th1 cells more advantageously than SEA. In conclusion, our study suggests that SEA is more likely than SWA to induce host immune responses, thus playing an important role in the development of schistosomiasis into chronic infectious diseases by stimulating immune effects and immune regulation (immunosuppression). Our results provide a theoretical basis for the prevention and control of schistosomiasis (vaccine research) and treatment (immunopathologic control), and also for the establishment of an immune research model using Schistosoma japonicum and its SWASEA antigen as a tool. And the extensive application in other immune-related diseases provides a more in-depth theoretical basis.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R392

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