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刚地弓形虫:对补体介导杀伤的抵抗机制

Toxoplasma gondii: mechanism of resistance to complement-mediated killing.

作者信息

Fuhrman S A, Joiner K A

机构信息

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

出版信息

J Immunol. 1989 Feb 1;142(3):940-7.

PMID:2643665
Abstract

Tachyzoites of the obligate intracellular protozoan Toxoplasma gondii are resistant to lysis in non-immune human serum. We have examined the mechanism of this serum resistance in RH and P strain organisms, which differ markedly in virulence, but are equally resistant to serum killing. Rapid, but limited, activation of the alternative complement pathway occurred in non-immune human serum, with deposition of equivalent amounts of C3 on the two strains. C component C3 bound covalently to parasite acceptor molecules via an ester linkage. The predominant form of C3 was iC3b which cannot participate in formation of a lytic C5b-9 complex. Multiple membrane constituents of the tachyzoite of T. gondii may serve as acceptors for the limited amount of C3 deposited during incubation in non-immune serum. When tachyzoites were presensitized with the lytic anti-p30 mAb 7B8, new amide-linked C3-acceptor complexes formed. Nearly equivalent C3 binding but a threefold enhancement of 125I-C9 binding occurred when mAb 7B8 pre-sensitized tachyzoites were compared to native organisms. These results indicate that tachyzoites of T. gondii are serum resistant because of failure to activate C efficiently. Presensitization with a lytic mAb alters the site of complement deposition and augments C5b-9 formation.

摘要

专性细胞内原生动物刚地弓形虫的速殖子对非免疫人血清中的溶解作用具有抗性。我们研究了RH和P株弓形虫血清抗性的机制,这两种菌株在毒力上有显著差异,但对血清杀伤同样具有抗性。在非免疫人血清中,替代补体途径迅速但有限地被激活,两种菌株上沉积的C3量相当。补体成分C3通过酯键与寄生虫受体分子共价结合。C3的主要形式是iC3b,它不能参与形成溶细胞性C5b-9复合物。刚地弓形虫速殖子的多种膜成分可能作为在非免疫血清中孵育期间沉积的有限量C3的受体。当速殖子用溶细胞性抗p30单克隆抗体7B8预致敏时,会形成新的酰胺连接的C3-受体复合物。与天然生物体相比,当用单克隆抗体7B8预致敏的速殖子进行比较时,C3结合量几乎相当,但125I-C9结合增强了三倍。这些结果表明,刚地弓形虫速殖子具有血清抗性是因为不能有效地激活补体。用溶细胞性单克隆抗体预致敏会改变补体沉积位点并增强C5b-9的形成。

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