INFLUENZA PATHOGENESIS & IMMUNOLOGY RESEARCH CENTER (IPIRC)

流感发病机制

• 批准号: 8172422
• 负责人: RICHARD W COMPANS
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172422
• 关键词: Animals; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; Computer Retrieval of Information on Scientific Projects Database; Development; Effector Cell; Environmental Risk Factor; Epitopes; Evolution; Funding; Grant; Human; Immune; Immune response; Immune system; Immunity; Immunology; Infection; Influenza; Influenza A virus; Influenza vaccination; Institution; Life; Lymphocyte; Molecular; Mus; Pathogenesis; Pathogenicity; Proliferating; Recruitment Activity; Research; Research Personnel; Resources; Retinal blind spot; Sanguisorba; Severities; Source; United States National Institutes of Health; Variant; Viral; Virus; Visit; improved; influenza virus strain; influenzavirus; novel; pandemic disease; response; transmission process

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 流感发病机制与免疫学研究中心 (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，包括研究具有大流行潜力的动物流感病毒；表征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。 大多数免疫反应遵循伯内特规则，即抗原从大量的细胞库中招募特定的淋巴细胞，并诱导它们增殖并分化为效应细胞。然而，“原始抗原原罪”现象与 Burnet 的 B 细胞参与规则相矛盾。人类在感染新型流感病毒株后，会产生针对较旧病毒株的抗体，但会损害对新型保护性抗原决定簇的反应。这加剧了当前感染的严重性。五十年前就描述了免疫系统的盲点以及对“原始抗原”而不是对新表位的反应的重定向。我们研究这个问题是为了确定变异流感病毒诱导原始抗原罪的程度。使用甲型流感病毒的两种相关毒株，我们发现原始抗原原罪导致保护性免疫的发展和对第二种病毒的回忆反应显着下降。 此外，我们已经能够证明，用两种活流感病毒株连续感染小鼠会导致对第一种病毒株几乎唯一的抗体反应，这表明原始抗原原罪可能是变异流感病毒颠覆免疫系统的潜在策略。