T CELL MEMORY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在感染艾滋病毒等病毒后，抗原从大量的T和B细胞中选择特定的淋巴细胞，并诱导它们选择性地增殖。这些被激活的淋巴细胞有助于快速清除抗原，在中和致病威胁后，它们作为记忆淋巴细胞在宿主体内持续一生。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，与伯内特的B细胞结合规则相矛盾。以前接触过流感病毒的人，一旦感染了一种新的流感病毒株，就会产生主要针对旧病毒株的抗体，而不是对新的保护性抗原决定因素的反应，从而加剧了当前感染的严重性。免疫系统的这种盲点和对“原始抗原”的反应重定向，而不是对当前病毒中的新表位的反应，是最近的报告所质疑的现象。因此，我们重新讨论了这一问题，以确定变异流感病毒在多大程度上诱发OAS。使用两种相关的甲型流感病毒株，我们已经证明OAS可以导致免疫记忆和回忆反应的发展显著下降。此外，我们还表明，连续感染活流感病毒株的小鼠几乎对第一种病毒株产生中和抗体反应，这表明OAS的诱导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. 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. Following infection with viruses such as HIV, antigens select specific lymphocytes from a large repertoire of T and B cells and induce them to selectively proliferate. These activated lymphocytes facilitate rapid antigen clearance and, upon neutralization of the pathogenic threat, they persist in the host as memory lymphocytes for a lifetime. 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. Humans previously exposed to influenza virus, upon infection with a novel influenza strain, produce antibodies directed primarily against the older viral strains at the expense of responses to novel protective antigenic determinants thus exacerbating the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original antigen," but not to novel epitopes in the current virus is a phenomenon which recent reports have questioned. Hence, we revisited this issue to determine the extent to which OAS is induced by variant influenza viruses. Using two related strains of influenza A viruses, we have shown that OAS can lead to a significant decrease in the development of immune memory and recall responses. In addition, we have shown that sequential infection of mice with live influenza virus strains leads to almost exclusive neutralizing antibody responses to the first viral strain suggesting that the induction of OAS could be a potential strategy by which variant influenza viruses subvert the immune system.