田鼠巴贝斯虫隐性感染小鼠试验及其对其他原虫共感染的影响

发布时间：2018-03-22 14:16

本文选题：田鼠巴贝斯虫　切入点：免疫系统　出处：《甘肃农业大学》2015年硕士论文　论文类型：学位论文

【摘要】：田鼠巴贝斯虫(Babesia microti)是引发人与啮齿动物巴贝斯虫病最主要的病原体,它是顶复门、梨形虫目、巴贝斯科、巴贝斯属的一种寄生于宿主红细胞内的血液原虫,主要经过硬蜱叮咬、输血或者血液制品等途径感染及传播,免疫力低的人或动物感染后表现出严重的临床症状,甚至导致死亡,一般宿主则多为隐性感染,成为传播来源。目前主要在美洲流行,近年来发病病例激增,同时在欧洲、亚洲等地方不断发现感染病例,在我国,已有人感染田鼠巴贝斯虫的报道,这一新发人兽共患病已经给畜牧业和人类健康带来了威胁。田鼠巴贝斯虫感染宿主后多数处于隐性感染状态,在宿主体内的增殖、分布和致病能力均研究较少,宿主的免疫反应以及是否会对其它病原体的再感染造成影响等方面都没有一个明确的研究结论。为此,本研究通过小鼠人工感染田鼠巴贝斯虫模型,调查隐性感染过程中虫体在宿主体内的增殖、组织器官分布和对宿主血液凝固的影响,同时对宿主的免疫反应以及与其他原虫共感染关系进行研究。通过对田鼠巴贝斯虫感染宿主后的荧光定量检测,结果表明田鼠巴贝斯虫可以在宿主体内长期存在且感染后期依然保持较高数量的虫体,同时在宿主的主要脏器组织均有分布。对感染后宿主凝血系统的研究表明田鼠巴贝斯虫可以通过影响内源性凝血系统使凝血时间缩短,这很容易引起一些血栓性疾病。抗体水平检测结果显示,在田鼠巴贝斯虫感染宿主后,抗体持续存在且处于一个较高的水平。通过流式细胞术对田鼠巴贝斯虫不同感染阶段T淋巴细胞亚群分化情况以及免疫细胞因子分泌水平做以研究,结果表明CD4+T细胞在控制田鼠巴贝斯虫的感染过程中发挥了重要作用,并且在感染前期,由Th1型免疫细胞介导的细胞免疫发挥了主导作用,感染后期则以体液免疫为主。通过对正常小鼠和脾脏摘除小鼠在田鼠巴贝斯虫感染后虫体增殖规律、血液生理指标、血清细胞因子分泌水平等多方面做了比较研究,结果表明对于脾脏摘除小鼠,田鼠巴贝斯虫可以引起更严重的感染,并且对其免疫系统和凝血系统产生更严重的影响,验证了免疫缺陷宿主的感染严重性。分别选取弓形虫(Toxoplasma gondii)和伊氏锥虫(Trypanosoma evansi)与田鼠巴贝斯虫构建人工共感染模型,结果表明田鼠巴贝斯虫感染后,可以显著的加重弓形虫的再感染,而对伊氏锥虫的再感染没有明显的影响。本研究对田鼠巴贝斯虫隐性感染和共感染的研究,将为其感染、传播、免疫以及致病机制等方面的研究开辟新的思路,为这一新发传染病的防控提供基础。
[Abstract]:The most common pathogen causing human and rodent Babes's disease is a haemoprotozoa of the genus Pheloptera, Pyriformes, Babesco, Babes, which is parasitic on the red blood cells of the host, mainly by ticks. Blood transfusions or blood products are transmitted by other means. People or animals with low immunity show serious clinical symptoms after infection, and even cause death. Most hosts are recessive infections and become sources of transmission. At present, they are mainly prevalent in the Americas. In recent years, there has been a sharp increase in the number of cases, and infections have been continuously found in Europe, Asia and other places. In China, there have been reports of people infected with Babes's vole. This new zoonosis has posed a threat to animal husbandry and human health. There is no clear conclusion about the host's immune response and whether it will affect the reinfection of other pathogens. To investigate the effects of insect body proliferation, tissue and organ distribution and blood coagulation on the host during recessive infection. At the same time, the immune response and co-infection with other protozoa were studied. The results showed that Babes could exist in the host for a long time and still maintain a high number of parasites in the later stage of infection. At the same time, the main organs of the host were all distributed. Studies on the coagulation system of the host after infection showed that Babes could shorten the coagulation time by affecting the endogenous coagulation system. It is easy to cause some thrombotic diseases. Antibody levels test results show that after the vole Babes infection host, The differentiation of T lymphocyte subsets and the secretion of immune cytokines were studied by flow cytometry in different infection stages of Babes's worm in voles. The results showed that CD4 T cells played an important role in the control of Babes's infection in voles, and the cellular immunity mediated by Th1 type immune cells played a leading role in the early stage of infection. In the later stage of infection, humoral immunity was the main factor. The rules of body proliferation, blood physiological index, serum cytokine secretion level and so on were compared between normal mice and spleen excised mice after the infection of Babes worm in voles. The results showed that Babes of vole could cause more serious infection and had a more serious effect on immune system and blood coagulation system in splenectomy mice. The infection severity of the immunodeficient host was verified. Toxoplasma gondii and Trypanosoma evansii) were selected to construct an artificial co-infection model with Babes's vole. The results showed that the infected mice were infected with Babes, and the results showed that the infected mice were infected with Toxoplasma gondii and Trypanosoma evansii. Toxoplasma gondii reinfection can be significantly aggravated, but there is no obvious effect on the reinfection of Trypanosoma evansi. In this study, the recessive infection and coinfection of Babes parasite in voles will be infected and transmitted. The study of immune and pathogenic mechanism provides a basis for the prevention and control of this new infectious disease.
【学位授予单位】：甘肃农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S855.9

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