结核分枝杆菌肝素结合血凝素的免疫作用研究

发布时间：2018-04-30 01:14

本文选题：结核分枝杆菌 + 肝素结合血凝素　；参考：《北京市结核病胸部肿瘤研究所》2008年硕士论文

【摘要】： 肝素结合血凝素(Heparin-binding hemagglutinin adhesin, HBHA)是结核分枝杆菌的一种菌体蛋白,是黏附素的一种,分子量约28kDa,其C末端富含赖氨酸,并在翻译后进行甲基化修饰,甲基化修饰对保证其免于蛋白酶的降解及保持其免疫特性有重要意义。HBHA是侵入呼吸道上皮细胞所需要的重要分子,其与上皮细胞的相互作用与肺外结核发病密切相关。国外的研究资料证明HBHA在不同结核感染状态的人群中,细胞免疫与体液免疫的反应不同,在潜伏感染者中可刺激外周血单个核细胞产生高水平的IFN-γ,提示有较好的免疫保护作用。本试验深入研究HBHA在不同结核感染状态人群中的免疫效应,探讨其免疫保护作用及在诊断方面的应用价值,实验用天然的HBHA、PPD等刺激不同结核感染状态人群的外周血单个核细胞,ELISA方法检测细胞培养上清液中的IFN-γ的浓度,用以判断细胞免疫反应的强度。用HBHA包被EIA平板,检测血清中的HBHA特异的IgG抗体水平,用以作为体液免疫反应的指标。结合细胞免疫及体液免疫来判断HBHA在不同感染状态人群中的免疫作用。实验结果显示,潜伏感染者中HBHA特异性的IFN-γ的浓度显著高于阴性对照组,略高于肺结核及肺外结核。肺结核及肺外结核患者间的HBHA、PPD刺激后的IFN-γ的浓度无显著差异。而血清抗体检测发现,肺结核患者的HBHA IgG抗体高于阴性对照及健康感染者,略高于肺外结核。即在潜伏感染者中是细胞免疫占优势而在结核病患者是体液免疫反应突出。实验证明HBHA有较好的免疫原性,其刺激潜伏感染者产生高水平的IFN-γ,提示潜伏感染者没有发病的原因可能与其免疫保护作用有关,同时也表明是HBHA相关的细胞免疫而非体液免疫可能对机体起保护作用。结合细胞免疫及体液免疫,有助于鉴别健康人群中的潜伏感染者,以进一步控制结核病。虽然HBHA对上皮细胞的黏附与肺外结核发病相关,但其相关的免疫反应在肺结核与肺外结核的鉴别上无显著差异。
[Abstract]:Heparin-binding hemagglutinin adhesin, HBHA) is a bacterial protein of Mycobacterium tuberculosis and a adhesion protein with molecular weight of about 28kDa.The C-terminal of heparin-binding hemagglutinin adhesin, HBHA) is rich in lysine and methylated after translation. Methylation modification plays an important role in protecting them from protease degradation and maintaining their immune properties. HBHA is an important molecule necessary for the invasion of respiratory epithelial cells and its interaction with epithelial cells is closely related to the pathogenesis of extrapulmonary tuberculosis. The results of foreign studies have proved that the response of cellular immunity to humoral immunity is different in different TB infected population. In latent infection group, HBHA can stimulate the production of high level IFN- 纬 in peripheral blood mononuclear cells, which suggests that HBHA has a better immune protective effect. In this study, we studied the immune effect of HBHA in different TB infected population, and discussed its protective effect and its application value in diagnosis. The concentration of IFN- 纬 in the supernatant of cell culture was detected by Elisa method in peripheral blood mononuclear cells (PBMC) stimulated by natural HBHAP PPD in order to judge the intensity of cellular immune response. EIA plate coated with HBHA was used to detect the level of HBHA specific IgG antibody in serum as an indicator of humoral immune reaction. Cellular immunity and humoral immunity were combined to evaluate the immune function of HBHA in different infected population. The results showed that the concentration of HBHA specific IFN- 纬 in latent infection was significantly higher than that in negative control group and slightly higher than that in pulmonary tuberculosis and extrapulmonary tuberculosis. There was no significant difference in IFN- 纬 between pulmonary tuberculosis and extrapulmonary tuberculosis after HBHAN PPD stimulation. Serum antibody test showed that HBHA IgG antibody in pulmonary tuberculosis patients was higher than that in negative controls and healthy individuals, and was slightly higher than that in extrapulmonary tuberculosis patients. In other words, cellular immunity is dominant in latent infection and humoral immune response is prominent in tuberculosis patients. The results show that HBHA has good immunogenicity, and it stimulates latent infection to produce high level of IFN- 纬, suggesting that the reason why latent infection does not develop may be related to its immune protection. It also suggests that HBHA-related cellular immunity rather than humoral immunity may protect the body. The combination of cellular immunity and humoral immunity can help to identify latent infections in healthy people and further control tuberculosis. Although the adhesion of HBHA to epithelial cells is related to the pathogenesis of extrapulmonary tuberculosis, there is no significant difference in the immunological response between pulmonary tuberculosis and extrapulmonary tuberculosis.
【学位授予单位】：北京市结核病胸部肿瘤研究所
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R392

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