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对经子孢子免疫的啮齿动物和人类志愿者体内重组恶性疟原虫环子孢子蛋白的细胞免疫和体液免疫反应。

Cellular and humoral immune responses to a recombinant P. falciparum CS protein in sporozoite-immunized rodents and human volunteers.

作者信息

Nardin E H, Nussenzweig R S, Altszuler R, Herrington D, Levine M, Murphy J, Davis J, Bathurst I, Barr P, Romero P

机构信息

Department of Medical and Molecular Parasitology, New York University School of Medicine, NY.

出版信息

Bull World Health Organ. 1990;68 Suppl(Suppl):85-7.

Abstract

The immune responses of sporozoite-immunized rodents and of human volunteers exposed to multiple bites of irradiated Plasmodium falciparum infected mosquitos have been investigated using a yeast-derived recombinant P. falciparum circumsporozoite (rPfCS) protein. The murine immune response to immunization with rPfCS was not genetically restricted. Nine different murine haplotypes, when immunized with rPfCS, developed high levels of antisporozoite antibodies detectable by IFA and RIA. In addition, injection of rPfCS induced a secondary antibody response in P. falciparum sporozoite-primed mice. Murine T-cell epitopes were mapped in the C terminus of the rPfCS protein using overlapping synthetic peptides. The human T-cell response was investigated using T-cell clones derived from peripheral blood lymphocytes (PBL) of a P. falciparum sporozoite-immunized volunteer. A total of 40 CD4+ T-cell clones were obtained. Stimulation indices ranged from 2.5 to 103.4 following challenge with rPfCS in the presence, but not in the absence, of antigen-presenting cells. The clones were specific for rPfCs and did not proliferate or secrete lymphokines when challenged with yeast-derived recombinant P. vivax or P. berghei CS protein or with a yeast-extract control. The clones also recognized the native CS protein in extracts of P. falciparum, but not P. berghei or P. cynomolgi, sporozoites.

摘要

利用酵母衍生的重组恶性疟原虫环子孢子蛋白(rPfCS),对经子孢子免疫的啮齿动物以及多次被辐照的感染恶性疟原虫的蚊子叮咬的人类志愿者的免疫反应进行了研究。小鼠对rPfCS免疫的免疫反应不受遗传限制。用rPfCS免疫的9种不同小鼠单倍型,产生了高水平的抗子孢子抗体,可通过免疫荧光法(IFA)和放射免疫分析法(RIA)检测到。此外,注射rPfCS可在经恶性疟原虫子孢子致敏的小鼠中诱导二次抗体反应。利用重叠合成肽在rPfCS蛋白的C末端定位了小鼠T细胞表位。使用源自经恶性疟原虫子孢子免疫的志愿者外周血淋巴细胞(PBL)的T细胞克隆研究了人类T细胞反应。共获得40个CD4 + T细胞克隆。在有抗原呈递细胞存在的情况下,用rPfCS刺激后,刺激指数范围为2.5至103.4,而在无抗原呈递细胞时则无此反应。这些克隆对rPfCs具有特异性,当用酵母衍生的重组间日疟原虫或伯氏疟原虫CS蛋白或酵母提取物对照进行刺激时,它们不会增殖或分泌淋巴因子。这些克隆还识别恶性疟原虫提取物中的天然CS蛋白,但不识别伯氏疟原虫或食蟹猴疟原虫子孢子提取物中的天然CS蛋白。

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