Nedrud J G, Liang X P, Hague N, Lamm M E
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1987 Nov 15;139(10):3484-92.
Based on the concept of a common mucosal immune system wherein mucosal associated lymphocytes traffic among the various mucous membranes, the murine gastrointestinal tract was immunized with Sendai virus antigens in order to elicit a virus-specific immune response in the respiratory tract. Multiple intragastric (oral) administration of live or killed Sendai virus induced IgA and IgG antiviral antibodies in both gastrointestinal secretions and serum. When cholera toxin as an adjuvant was included along with virus, gut IgA and IgG as well as serum IgA responses were enhanced. Antiviral antibodies induced in respiratory secretions by oral killed virus plus cholera toxin, however, were variable and protection from virus challenge was not demonstrated. Significantly higher levels of respiratory antiviral antibodies were induced if immunization with oral killed Sendai virus/cholera toxin was combined with intranasal administration of small amounts of killed virus. The combined immunization also resulted in protection of both the upper and lower respiratory tracts from virus infection. Protection of the upper respiratory tract was correlated with the presence of IgA antiviral antibodies in nasal washings. On the other hand, protection of the lower respiratory tract was correlated with IgG antiviral antibodies in bronchoalveolar lavage fluids. Immunization with intranasal killed virus alone conferred partial protection to the lower respiratory tract and no protection to the upper respiratory tract. Thus, oral immunization with killed virus antigen could prime for a protective immune response in the murine respiratory tract and this protective response included IgA antibodies.
基于共同黏膜免疫系统的概念，即黏膜相关淋巴细胞在不同黏膜之间循环，用仙台病毒抗原免疫小鼠胃肠道，以在呼吸道引发病毒特异性免疫反应。多次胃内（口服）给予活的或灭活的仙台病毒可在胃肠道分泌物和血清中诱导产生IgA和IgG抗病毒抗体。当霍乱毒素作为佐剂与病毒一起使用时，肠道IgA和IgG以及血清IgA反应增强。然而，口服灭活病毒加霍乱毒素在呼吸道分泌物中诱导产生的抗病毒抗体并不稳定，且未证明对病毒攻击有保护作用。如果将口服灭活仙台病毒/霍乱毒素免疫与鼻内给予少量灭活病毒相结合，则可诱导产生显著更高水平的呼吸道抗病毒抗体。联合免疫还可使上、下呼吸道免受病毒感染。上呼吸道的保护与鼻洗液中IgA抗病毒抗体的存在相关。另一方面，下呼吸道的保护与支气管肺泡灌洗液中的IgG抗病毒抗体相关。单独用鼻内灭活病毒免疫可对下呼吸道提供部分保护，但对上呼吸道无保护作用。因此，用灭活病毒抗原进行口服免疫可引发小鼠呼吸道的保护性免疫反应，且这种保护性反应包括IgA抗体。
