Passive transfer of local immunity to influenza virus infection by IgA antibody.

Passive transfer of local immunity to influenza virus infection by IgA antibody.
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DOI:
10.4049/jimmunol.146.6.1972
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发表时间:
1991-03
影响因子:
4.4
通讯作者:
K. B. Renegar;P. Small
K. B. Renegar;P. Small
中科院分区:
医学2区
文献类型:
--
作者:
K. B. Renegar;P. Small

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许多研究表明,保护作用与分泌型 IgA 滴度之间存在相关性,因此推测分泌型 IgA 是粘膜免疫的介质;然而,因果关系尚未建立。传统上,抗体的被动转移已被用来证明因果关系,但之前尚未报道过生理运输的 IgA 带来的局部免疫的被动转移。在这项研究中,小鼠静脉注射了针对 PR8 流感病毒 H1 血凝素的聚合 IgA (pIgA)、单体 IgA (mIgA) 或 IgG1 mAb。与 mIg 相比,pIgA 被证明可以特异性转运至鼻腔分泌物中。所运输的 pIgA 具有功能性,其在 ELISA 测定中与病毒结合的能力以及保护非免疫小鼠免受 H1N1 而非 H3N2 流感病毒鼻内感染的能力证明了这一点。静脉注射类似病毒中和剂量的抗流感 IgG1 mAb 并不能预防鼻腔病毒攻击。 IgA 介导的保护可以通过鼻内施用抗 IgA α 链的抗血清来消除。这些数据证明了静脉注射局部免疫力的被动转移。给予pIgA抗体并显示分泌物中的IgA可以预防流感病毒感染。这种通用方法可以为评估局部 IgA 在宿主防御其他病原体中的作用提供模型。
Secretory IgA is presumed to be the mediator of mucosal immunity based on many studies that show a correlation between protection and secretory IgA titers; however, a causal relationship has not yet been established. Classically, passive transfer of antibody has been used to demonstrate causality, but the passive transfer of local immunity with physiologically transported IgA has not been previously reported. In this study mice were injected intravenously with polymeric IgA (pIgA), monomeric IgA (mIgA), or IgG1 mAb specific for the H1 hemaglutinin of PR8 influenza virus. pIgA was shown to be specifically transported into nasal secretions relative to the mIg. The transported pIgA was functional, as evidenced by its ability to bind to virus in an ELISA assay and to protect nonimmune mice against intranasal infection with H1N1 but not H3N2 influenza virus. Intravenous injection of similar virus-neutralizing doses of anti-influenza IgG1 mAb did not protect against nasal viral challenge. IgA-mediated protection could be abrogated by the intranasal administration of antiserum against the alpha chain of IgA. These data demonstrate the passive transfer of local immunity by the i.v. administration of pIgA antibody and show that the IgA in secretions can protect against influenza virus infection. This general approach could provide a model for the evaluation of the role of local IgA in host defense against other pathogens.