Basic Research on Protective Immunity against Experimental Hemoprotozoan Infections

本研究利用小鼠模型研究了细胞免疫在巴贝斯虫感染中的作用。在致死性罗氏巴贝斯虫感染中，药物治愈的小鼠对罗氏巴贝斯虫攻击感染的保护率为75%，体液免疫似乎在免疫的效应期发挥了主要作用。一次感染巴贝斯虫药物治愈的小鼠在攻击感染后存活，对拉氏念珠菌感染表现出100%的保护作用，Lyt1^+和Lyt2^+T细胞可能有助于控制二次感染。在B.microti感染中，虽然小鼠有较高的寄生虫血症，但从初次感染中自然恢复，nu/nu小鼠和SCID小鼠的寄生虫血症峰值较高，未能清除感染。这些结果表明，T淋巴细胞是解决微小巴氏杆菌感染所必需的。用单抗去除CD_4~+T细胞的小鼠的寄生虫血症较高，感染控制失败，而CD_8~+T细胞耗尽的小鼠出现…。对感染病程无明显影响。对照组和CD8^+细胞耗竭的脾细胞培养上清液显示高浓度的干扰素-γ，而不是CD4^+耗竭小鼠的脾细胞培养上清液。用抗干扰素-γ单抗治疗感染的小鼠，其寄生虫血症明显高于对照组。这些结果提示，小鼠感染微小杆菌后产生的干扰素-γ至少在一定程度上起到了控制微小杆菌急性感染的作用。识别微小杆菌70、30 kDa抗原的单抗是用罗氏杆菌攻击小鼠产生的。给予单抗可延缓小鼠寄生虫病的发病。暴露于猫等孢子虫卵囊的小鼠在暴露卵囊后第28天对微小芽孢杆菌感染表现出绝对抵抗力。费氏巴贝斯虫感染诱导的CD4~+T细胞对小鼠具有保护作用。观察了两种巴贝斯虫病小鼠肾脏和肝脏的病理变化。罗德海尼杆菌感染对肾脏和肝脏的损害比微小杆菌感染严重。肾小球系膜基质和肾小球基底膜均有电子致密沉积，免疫组织化学显示这些沉积为免疫复合体。较少

Role of cell-mediated immunity in Babesia infection was investigated using mouse models in the present study. In lethal Babesia rodhaini infection, drug-cured mice showed 75% protection against challenge infection with B.rodhaini and a humoral immunity appears to be major role in the effector phase of immunity. Mice which were cured first infection with anti-Babesia durg and survived with challenge infection, showed 100% protection against B.radhaini infection, Lyt1^+ and Lyt2^+ T cells may contribute in controlling secondary infection.In B.microti infection, while mice sufferd high parasitemia, but recovered naturally from their primary infection, nu/nu mice and SCID had a higher peak parasitemia and failed to clear the infection. These results demonstrated that T lymphocytes are necessary for the resolution of B.microti infection. Mice depleted of CD4^+ T cells with monoclonal antibody (mAb) had high parasitemia and failed to control the infection, while depletion of CD8^+ cells had … More no effect on the course of infection. Culture supernatants of spleen cells from control and CD8^+ cells depleted, but not from CD4^+ depleted mice, showed high concentration of IFN-gamma. Treatment of infected mice with anti-IFN-gamma mAb showed higher parasitemia than that of the control group. These results suggest that IFN-gamma produce by CD4^+ T cells, at least in part, is responsible for the control of acute infection with B.microti in mice.Mab, recognizing 70,30 kDa antigens of B.microti and challenged with B.rodhaini, was produced from mice infected with B.microti and challenged with B.rodhaini. Administration of the mAb gave the delay of onset of parasitemias in mice. Mice which were exposed to oocysts of Isospora felis, showed absolute resistance against B.microti infection on 28th day post-exposure of oocysts. CD4^+ T cells induced by I.felis infection provides mice protection against B.microti.Pathological changes were examined in the kidneys and liver of mice of two babesioses. Severe damages to kidneys and liver were observed in B.rodhaini infection rather than in B.microti infection. Electron-dense deposits were demonstrated in the mesangial matrix and along the glomerular basement membrane and these deposits were suggested as immune complexes by immunohistochemistry. Less