肝素诱导性血小板减少症的免疫学研究

发布时间：2018-09-07 08:54

【摘要】：肝素诱导性血小板减少症(HIT)是由于机体产生了针对血小板因子4(PF4)/肝素复合物的特异性抗体而诱发的免疫性疾病。由PF4,肝素,以及PF4/肝素复合物特异性抗体所组成的免疫复合物是HIT发病机制的关键因素。目前对于HIT的发病机制尚未完全清楚,本课题将在免疫学角度对HIT进行深入探讨,希望能进一步加深对HIT发病机理的理解。通过建立小鼠的HIT免疫模型,成功诱导小鼠产生出针对PF4/肝素复合物的特异性抗体。在此小鼠模型的基础上,我们发现小鼠脾脏边缘区B淋巴细胞在PF4/肝素复合物特异性抗体的生成过程中起着关键性作用。在缺少边缘区B淋巴细胞的小鼠体内,免疫过后所产生的PF4/肝素复合物特异性抗体水平明显低于对照组小鼠。此外,我们还发现HIT的发病受机体的免疫耐受所调控。在健康人群以及野生型小鼠体内存在抗原耐受的PF4/肝素复合物特异性B淋巴细胞,此类细胞在受到刺激的情况下能转化为合成抗体的浆细胞合成并分泌致病性抗体。最后,我们还发现作为体液免疫的协助者-辅助性T淋巴细胞,参与了PF4/肝素复合物特异性抗体合成的过程。若将小鼠体内的T淋巴细胞通过免疫学方法剔除,将影响PF4/肝素复合物特异性抗体的合成。综上所述,本课题在免疫学的角度通过多个不同的层面对HIT进行深入剖析,希望以此进一步加深对HIT发病机制的理解。
[Abstract]:Heparin-induced thrombocytopenia (HIT) is an immune disease induced by the production of specific antibodies against platelet factor 4 (PF4) / heparin complex. The immune complex composed of PF4, heparin and PF4/ heparin complex is a key factor in the pathogenesis of HIT. At present, the pathogenesis of HIT has not been fully understood, this topic will be in the immunological perspective of HIT in-depth study, hoping to further understand the pathogenesis of HIT. The HIT immune model of mice was established and the specific antibody against PF4/ heparin complex was successfully induced. On the basis of this mouse model, we found that B lymphocytes in the marginal region of mouse spleen play a key role in the formation of specific antibodies against PF4/ heparin complex. In mice lacking borderline B lymphocytes, the specific antibody level of PF4/ heparin complex produced after immunization was significantly lower than that of control mice. In addition, we also found that the pathogenesis of HIT is regulated by immune tolerance. There are antigen-tolerant PF4/ heparin complex specific B lymphocytes in healthy population and wild-type mice, which can be transformed into plasmacyte to synthesize and secrete pathogenic antibody under stimulation. Finally, we also found that, as a helper of humoral immunity, helper T lymphocytes were involved in the synthesis of specific antibodies against PF4/ heparin complex. If T lymphocytes in mice were removed by immunological method, the synthesis of specific antibodies against PF4/ heparin complex would be affected. To sum up, in the immunological point of view, the topic through a number of different levels of in-depth analysis of HIT, hoping to further understand the pathogenesis of HIT.
【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R558.2

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