B CELL MEMORY AND ORIGINAL ANTIGENIC SIN

B 细胞记忆和原罪抗原

• 批准号: 8357483
• 负责人: JOSHY JACOB
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357483
• 关键词: Activated Lymphocyte; Antigens; B-Lymphocytes; Data Analyses; Funding; Grant; Human; Immune response; Immunology; Influenza; Life; Lymphocyte; Memory; Memory B-Lymphocyte; Mus; National Center for Research Resources; Primates; Principal Investigator; Proliferating; Research; Research Infrastructure; Resources; Sanguisorba; Scheme; Source; T-Lymphocyte; United States National Institutes of Health; Vaccinated; Vaccine Research; cohort; cost; influenza virus vaccine; influenzavirus; pandemic influenza; response; theories

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. Burnet's clonal selection theory, the reigning paradigm in immunology, dictates that antigen selects specific lymphocytes from a large repertoire of T and B cells and induces them to selectively proliferate. These activated lymphocytes facilitate rapid antigen clearance and, upon neutralization of the antigenic threat, they persist in the host as memory lymphocytes for a lifetime. Later in life, encounter with the same antigen induces massive proliferation of these memory lymphocytes and rapid clearance of the antigen. While this scheme holds true for most immune responses, the phenomenon of "original antigenic sin", first described in humans vaccinated against influenza virus, stands out as a paradox to Burnet's rules of B cell engagement (Fazekas de St and Webster, 1966a). This project seeks to understand B cell memory as it relates to original antigenic sin responses to both strains and subtypes of influenza virus. Since original antigenic sin can drastically dampen immune responses to newer strains of influenza it is critical to understand the fundamentals of this phenomenon as this has tremendous implications for influenza vaccine research particularly with pandemic influenza looming on the horizon. In order to investigate the mechanism of original antigenic sin we have immunized cohorts of mice with inactivated influenza viruses, and we continue to collect and analyze the data concerning their immune responses.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 伯内特的克隆选择理论是免疫学的主导范式，它规定抗原从大量T和B细胞中选择特异性淋巴细胞，并诱导它们选择性增殖。这些活化的淋巴细胞促进快速抗原清除，并且在中和抗原威胁后，它们在宿主中作为记忆淋巴细胞持续一生。在以后的生活中，遇到相同的抗原诱导这些记忆淋巴细胞的大量增殖和抗原的快速清除。虽然这一方案适用于大多数免疫应答，但首次在接种流感病毒疫苗的人类中描述的“原始抗原罪”现象突出为伯内特的B细胞接合规则的悖论（Fazekas de St和韦伯斯特，1966 a）。这个项目试图了解B细胞记忆，因为它涉及到原始抗原的sin反应，无论是株和亚型的流感病毒。由于抗原原罪可以大大抑制对新流感病毒株的免疫反应，因此了解这种现象的基本原理至关重要，因为这对流感疫苗研究具有巨大影响，特别是在大流行性流感即将来临的情况下。为了研究抗原原罪的机制，我们用灭活的流感病毒免疫小鼠队列，并继续收集和分析有关其免疫应答的数据。