CELL MEDIATED IMMUNITY IN INFLUENZA

汉坦病毒和抗药性的最新经验 结核病强调了我们对呼吸道病原体的脆弱性。 我们忘记了本世纪最大的病毒大流行是由 一种甲型流感病毒，这些病毒导致大量 每年都有人。豁免权是我们唯一的保护：没有多少 行为改变可以防止高度传染性疾病的传播 城市人口中的呼吸道病毒。尽管如此，为数不多的 可获得的疫苗是次优的，反映出我们基本缺乏 了解如何最好地促进有效的免疫反应 呼吸道粘膜。这一建议延续了系统的、量化的 小鼠肺和淋巴组织中细胞事件的解剖 感染了甲型流感病毒。大量的、新颖的信息具有 出现在前一个资助期。这在体内得到了严格的发展 事实证明，模型在显示微妙但重要的效果方面具有巨大价值 例如，在基因打乱的“基因敲除”小鼠身上。正在进行的 实验集中在对反应的进一步定义上 病毒特异性CD_4~+和CD_4~(2+)的特性和效应机制 CD8+α-βT细胞受体(TCR)+淋巴细胞的命运 细胞和各种细胞因子的作用。分析将不可避免地 提供对细胞免疫本质的进一步洞察 一般情况下，病毒清除的特点与病理相关 这种免疫反应，并提出了免疫力可能是 通过操纵正常的寄主抗性机制来增强。

Recent experience with the hantaviruses and with drug-resistant tuberculosis has emphasized our vulnerability to respiratory pathogens. We forget that the greatest virus pandemic in this century was caused any an influenza A virus, and that these viruses kill substantial numbers of people each year. Immunity is our only protection: no amount of behavioral modification can prevent the spread of a highly infectious respiratory virus within urban populations. Despite this, the few vaccines that are available are sub-optimal, reflecting our basic lack of understanding of how best to promote an effective immune response at the respiratory mucosa. This proposal continues the systematic, quantitative dissection of the cellular events in the lung and lymphoid tissue of mice infected with influenza A viruses. Substantial, novel information has emerged in the previous funding period. This rigorously developed in vivo model is proving of great value for showing subtle, but important, effects in (for instance) genetically disrupted "knock-out" mice. The on-going experiments concentrate on the further definition of the response characteristics and effector mechanisms used by virus-specific CD4+ and CD8+ alpha beta T cell receptor (TCR)+ lymphocytes, the fate of these T cells and the roles of various cytokines. The analysis will inevitably provide further insights into the nature of cell-mediated immunity in general, the characteristics of virus clearance and pathology associated with this immune response, and suggest ways that immunity might be enhanced by manipulating normal host resistance mechanisms.