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共同黏膜免疫系统:从基本原理到与女性生殖道相关的肠道疫苗

The common mucosal immune system: from basic principles to enteric vaccines with relevance for the female reproductive tract.

作者信息

McGhee J R, Xu-Amano J, Miller C J, Jackson R J, Fujihashi K, Staats H F, Kiyono H

机构信息

Department of Microbiology, UAB Medical Center, Birmingham, Alabama 35294.

出版信息

Reprod Fertil Dev. 1994;6(3):369-79. doi: 10.1071/rd9940369.

DOI:10.1071/rd9940369
PMID:7831485
Abstract

The realization that induction of immune responses at mucosal surfaces may prevent colonization, invasion or dissemination of pathogenic microorganisms has spurred intensive efforts to develop vaccines which elicit effective mucosal immunity. In this paper, recent results are discussed for mice given cholera toxin as both an immunogen and as an adjuvant for inducing both humoral and gastrointestinal mucosal immune responses. Oral administration of cholera toxin alone or with a co-administered protein vaccine tetanus toxoid induces a strong T helper type 2 (TH2) cell response in both Peyer's patches and spleen. Both serum IgG and secretory IgA antibodies specific for cholera toxin or for the co-administered protein tetanus toxoid were induced. When administered parentally, however, no mucosal antibody responses were evident and a mixed TH1- and TH2-type CD4+ T cell response was noted in the spleen. Various vectors are being employed in an effort not only to induce mucosal immune responses but also to direct the response to a TH1-type response, thought to promote strong cell-mediated immune responses, or to a TH2-type response for maximum B cell antibody responses. The ability to manipulate the TH cell responses may provide a more rational approach for the design of vaccines. Although lymphoid tissues of the female reproductive tract differ from that of the gut, many of the strategies and evolving principles may be directly applicable to the development of vaccines designed to prevent sexually transmitted diseases.

摘要

认识到在黏膜表面诱导免疫反应可能预防致病微生物的定植、侵袭或播散,这促使人们大力研发能引发有效黏膜免疫的疫苗。本文讨论了给小鼠注射霍乱毒素作为免疫原和佐剂以诱导体液免疫和胃肠道黏膜免疫反应的最新结果。单独口服霍乱毒素或与共同给药的蛋白疫苗破伤风类毒素一起口服,均可在派尔集合淋巴结和脾脏中诱导强烈的2型辅助性T细胞(TH2)反应。诱导产生了针对霍乱毒素或共同给药的蛋白破伤风类毒素的血清IgG和分泌型IgA抗体。然而,经肠道外给药时,未出现明显的黏膜抗体反应,且在脾脏中观察到混合的TH1型和TH2型CD4 + T细胞反应。目前正在使用各种载体,不仅是为了诱导黏膜免疫反应,而且是为了将反应导向促进强烈细胞介导免疫反应的TH1型反应,或导向产生最大B细胞抗体反应的TH2型反应。操纵TH细胞反应的能力可能为疫苗设计提供更合理的方法。尽管女性生殖道的淋巴组织与肠道不同,但许多策略和不断发展的原则可能直接适用于预防性传播疾病疫苗的研发。

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Reprod Fertil Dev. 1994;6(3):369-79. doi: 10.1071/rd9940369.
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Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses.用重组沙门氏菌菌株或霍乱毒素对白细胞介素-4(IL-4)基因敲除小鼠进行口服免疫,结果显示,产生IL-6和IL-10的CD4 + Th2细胞与黏膜免疫球蛋白A反应相关。
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