INFLUENZA PATHOGENESIS & IMMUNOLOGY RESEARCH CENTER (IPIRC)

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 流感发病和免疫研究中心(IPIRC)是由NIH/NIAID资助的六个国家流感卓越中心之一。该中心的目标是确定影响流感病毒进化、出现、传播和致病性的分子、生态和/或环境因素，包括对具有大流行潜力的动物流感病毒的研究；并确定流感疫苗接种的免疫反应特征，以加强对保护和交叉保护的免疫相关性的了解。 大多数免疫反应遵循伯内特规则，即抗原从一个大的谱系中招募特定的淋巴细胞，并诱导它们增殖和分化为效应细胞。然而，“原始性原罪”现象与伯内特的B细胞结合规则是矛盾的。人类一旦感染了一种新型流感病毒株，就会产生针对旧病毒株的抗体，代价是对新的保护性抗原决定簇的反应。这加剧了当前感染的严重性。我们访问这一问题是为了确定变异流感病毒在多大程度上诱导原始抗原性犯罪。使用两个相关的甲型流感病毒株，我们发现原始抗原性SIN导致对第二种病毒的保护性免疫和回忆反应的发展显著降低。 此外，我们已经能够证明，连续感染两种活的流感病毒株的小鼠可以导致对第一种病毒株的几乎唯一的抗体反应，这表明原始抗原性SIN可能是一种潜在的策略，通过这种策略，变异的流感病毒可以颠覆免疫系统。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Influenza Pathogenesis & Immunology Research Center (IPIRC) is one of six national Influenza Centers of Excellence funded by NIH/NIAID. The objectives of this Center are to determine the molecular, ecologic and/or environmental factors influencing the evolution, emergence, transmission and pathogenicity of influenza viruses, including studies on animal influenza viruses with pandemic potential; and to characterize the immune response to influenza vaccination to improve understanding of immune correlates of protection and cross-protection. Most immune responses follow Burnet's rule, that antigen recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce antibodies against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. We visited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we have shown that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we have been able to show that sequential infection of mice with two live influenza virus strains leads to almost exclusive antibody responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.