本文關(guān)鍵詞： 日本血吸蟲 成蟲抗原 蟲卵抗原 免疫效應(yīng) 免疫調(diào)控　出處：《南京醫(yī)科大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】：在我國,血吸蟲病仍然是當(dāng)今主要公共衛(wèi)生問題之一。血吸蟲病是一種典型的慢性感染性、免疫性疾病,在血吸蟲感染過程的不同時期機體免疫系統(tǒng)針對血吸蟲各發(fā)育階段的不同抗原產(chǎn)生不同的優(yōu)勢免疫應(yīng)答。成蟲抗原(SWA)、蟲卵抗原(SEA)是血吸蟲感染過程中最主要的兩種抗原成分。自然感染過程中,這兩類抗原共同存在、作用相互疊加相互影響,結(jié)果更為復(fù)雜。因此,為研究這兩種抗原在血吸蟲感染后的宿主的免疫效應(yīng)和免疫負調(diào)控中的異同作用,我們首先通過體內(nèi)外實驗觀測SWA和SEA對小鼠脾細胞、CD4~+T淋巴細胞的增殖、分化等免疫效應(yīng)發(fā)生發(fā)展中的重要因素的不同影響;其次,通過體內(nèi)外實驗觀測SWA和SEA刺激小鼠CD4~+T淋巴細胞凋亡和誘導(dǎo)CD4~+CD25~+Treg細胞并產(chǎn)生免疫抑制因子等免疫負調(diào)控中的重要因素的不同作用。結(jié)果發(fā)現(xiàn):與SWA相比,SEA更易刺激脾細胞增殖(p0.01),且SEA也更易刺激CD4~+T淋巴細胞增殖(p0.05)。同時,流式細胞術(shù)結(jié)果檢測顯示,與SWA相比,SEA能更好地刺激脾細胞及其中的CD4~+T淋巴細胞亞群產(chǎn)生IL-4和IL-17(p0.05),但SEA刺激產(chǎn)生IFN-γ的能力顯著較SWA低(p0.05)。凋亡檢測結(jié)果顯示,SWA、SEA均能刺激CD4~+T淋巴細胞的凋亡,但二者差異無統(tǒng)計學(xué)意義(p0.05);進一步觀測兩種抗原誘導(dǎo)CD4~+CD25~+FOXP3~+Treg細胞的比例變化時發(fā)現(xiàn),SEA能比SWA誘導(dǎo)更高比例的CD4~+CD25~+FOXP3~+Treg細胞(p0.05),且SEA比SWA刺激CD4~+CD25~+Treg細胞免疫抑制功能的能力可能也更強(p0.05);SWA、SEA免疫小鼠后,SEA顯示其刺激CD4~+CD25~+Treg細胞產(chǎn)生IL-10、TGF-β的能力更高(p0.001)。上述結(jié)果提示,SEA比SWA更易刺激脾細胞和CD4~+T淋巴細胞的增殖、更能優(yōu)勢誘導(dǎo)Th2和Th17細胞的分化以發(fā)揮免疫效應(yīng)作用、并能更好地活化誘導(dǎo)CD4~+CD25~+Treg細胞發(fā)揮免疫抑制作用。但是,SWA比SEA更能優(yōu)勢誘導(dǎo)Th1細胞的分化。 總之,我們的研究提示SEA較SWA更易誘導(dǎo)宿主產(chǎn)生免疫反應(yīng),從而通過刺激免疫效應(yīng)與免疫調(diào)節(jié)(免疫抑制)兩方面在血吸蟲病發(fā)展為慢性感染性疾病中發(fā)揮重要作用,我們的研究結(jié)果為血吸蟲病的防控(疫苗研究)和治療(免疫病理控制)提供了理論依據(jù),同時,也為建立以血吸蟲及其SWA、SEA抗原為工具的免疫研究模型、并在其它免疫相關(guān)疾病領(lǐng)域中的廣泛應(yīng)用提供了更深入的理論依據(jù)。
[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- 緯 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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R392

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本文編號：1523564