Basic Research on Protective Immunity against Experimental Hemoprotozoan Infections

实验性血液原虫感染的保护性免疫基础研究

• 批准号: 03660318
• 负责人: IGARASHI Ikuo
• 金额: $ 1.47万
• 依托单位: The Research Center for Protozoan Molecular Immunology, Obihiro University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03660318/
• 关键词: Murine Babesia; Protective immunity; CD4^+ T cells; Gamma interferon; Cross-reactive antigen; Renal pathology; Immunopathology; Nonspecific immunity; バベシア原虫; 感染防御; CD_4陽性細胞; ガンア-インターフェロン; 赤血球内寄生原虫; 感染防抑; CD4^+細胞; 感染防御免疫

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

在本研究中，使用小鼠模型研究了细胞介导的免疫学在Babesia感染中的作用。在致命的巴贝西亚·罗德尼（Babesia Rodhaini）感染中，药物固定小鼠显示75％的防御性侵害性感染，而体液中的免疫学似乎是免疫学效应阶段的主要作用。首次用抗巴贝斯Durg治愈并在挑战感染中幸存下来的小鼠显示100％防止b.radhaini感染，Lyt1^+和Lyt2^+ T细胞可能有助于控制继发性感染。Microtib.microti感染，而小鼠却遭受了高寄生虫的峰值，而自然而然地恢复了原发性和NU的NU，NOU和SCID均为NUIMICE，并恢复了MIC。未能清除感染。这些结果表明，T淋巴细胞对于分辨率链球菌感染是必需的。用单克隆抗体（MAB）加深了CD4^+ T细胞加深的小鼠患有高寄生虫血症，无法控制感染，而CD8^+细胞的耗竭对感染过程没有影响。来自对照和CD8^+细胞的卵形细胞的培养上清液耗尽，但没有从CD4^+耗尽的小鼠中培养，显示出高浓度的IFN-GAMMA。用抗IFN-gamma mAb治疗感染的小鼠的寄生虫比对照组更高。这些结果表明，CD4^+ T细胞产生的IFN-gamma至少部分是为了控制小鼠中用b.microti的急性感染。MAB，识别70,30 kDa抗原b.microti的抗原，并挑战了B.rodihaini的挑战，并由B.rodihaini产生了由B.microti和B. miciroti和B.Rodihihihih b. rodihih的小鼠产生的。 MAB的给药延迟了小鼠寄生虫的发作。暴露于等孢子的卵囊的小鼠在卵囊暴露后第28天对米卡特氏菌感染具有绝对抗性。由i.felis感染诱导的CD4^+ T细胞可提供针对b.microti的小鼠保护。在rodhaini感染中观察到肾脏和肝脏的严重损害，而不是在麦克罗氏芽孢杆菌感染中。电子致密的沉积物在肾小球基质和肾小球基底膜中被证明，并通过免疫组织化学建议这些沉积物作为免疫复合物。较少的

项目成果

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K.Miyahara：“弓形虫裂解物抗原对甲基胆蒽诱导的荷瘤大鼠的抗肿瘤活性。”

Shimada, T., Igarashi, I., Maki, Y., Claveria, F.G., Saito, A.and Suzuki, N.: "Cellular subsets involved in protective immunity to Babesia rodhaini infection in BLAB/c mice." J.Protozool.Res.1. 35-44 (1991)

Shimada, T.、Igarashi, I.、Maki, Y.、Claveria, F.G.、Saito, A. 和 Suzuki, N.：“参与 BLAB/c 小鼠对巴贝虫感染的保护性免疫的细胞亚群。”

Igarashi, I., Hosomi, T., Kaidoh, T., Omata, Y., Saito, A.Suzuki, N.and Aikawa, M.: "Comparison of damage to kidneys and liver caused by lethal Babesia rodhaini infection and non-lethal Babesia microti infection in mice." J.Protozool.Res.3. 144-155 (1993)

Igarashi, I.、Hosomi, T.、Kaidoh, T.、Omata, Y.、Saito, A.Suzuki, N. 和 Aikawa, M.：“致死性巴贝虫罗德海尼感染和非致命性巴贝虫感染对肾脏和肝脏造成的损害的比较

A.Saito: "Effects of reactive oxygen intermediate scavengers on the antitoxoplasmic activity of activated macrophages" Parasitology Research. 78. 28-31 (1992)

A.Saito：“活性氧中间体清除剂对活化巨噬细胞抗弓形虫活性的影响”寄生虫学研究。

Inoue, N., Omata, Y., Igarashi, I., Saito, A., Claveria, F.G.and Suzuki, N.: "Babesia rodhaini and Babesia microti : Cross-Immunity and Cross-Antigens." J.Protozool.Res.4. 98-104 (1994)

Inoue, N.、Omata, Y.、Igarashi, I.、Saito, A.、Claveria, F.G. 和 Suzuki, N.：“罗德海尼巴贝虫和田鼠巴贝虫：交叉免疫和交叉抗原。”