INFLUENZA PATHOGENESIS & IMMUNOLOGY RESEARCH CENTER (IPIRC)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 流感发病机制和免疫学研究中心（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;并描述流感疫苗接种的免疫反应，以提高对保护和交叉保护的免疫相关性的理解。 大多数免疫应答遵循伯内特法则，即抗原从大量库中募集特异性淋巴细胞，并诱导它们增殖和分化为效应细胞。然而，“原始抗原罪”的现象作为伯内特的B细胞接合规则的悖论而突出。人类在感染新型流感病毒株后，产生针对旧病毒株的抗体，代价是对新型保护性抗原决定簇的应答。这加剧了当前感染的严重性。免疫系统的这个盲点和对“原始抗原”而不是新表位的反应的重定向在50年前就被描述过。我们访问这个问题，以确定在何种程度上原始抗原罪是由变异流感病毒诱导。使用两个相关的甲型流感病毒株，我们表明，原始抗原罪孽导致显着减少保护性免疫和回忆反应的发展，第二个病毒。 此外，我们已经能够表明，连续感染两种活流感病毒株的小鼠几乎只对第一种病毒株产生抗体反应，这表明原始抗原性罪恶可能是变异流感病毒破坏免疫系统的潜在策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 have been to determine the molecular, ecologic and/or environmental factors that influence 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 the immune correlates of protection and cross-protection. Most immune responses follow Burnet's rule in 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. This blind spot of the immune system and the redirection of responses to the "original antigen" rather than to novel epitopes were described fifty years ago. 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 show 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.