Contribution of dendritic cell paralysis to the immunosuppression associated with systemic infections

免疫系统利用产生抗体的B细胞和杀伤性T细胞对抗病毒和其他感染。B细胞和杀伤T细胞是由免疫系统的特殊细胞树突状细胞（DC）吸收的。DC分布在全身，在那里它们扮演着免疫监视的角色：它们不断监测周围病原体的存在。当DC检测到这些病原体时，它们就会被激活。它们捕获病原体，将其分解成称为抗原的小块，并将这些抗原展示在它们的表面，在那里它们可以被辅助T细胞看到，从而动员B细胞和杀伤T细胞。这一连串的反应引发了免疫反应。DC在检测到病原体后发生了深刻的变化。它们停止对周围环境的监测，集中精力向T细胞展示触发它们最初激活的病原体的抗原。事实上，它们对新的病原体没有反应。在正常情况下，每次遇到病原体都会激活很少的DC，因此总是有足够的DC准备应对新的感染。然而，在某些情况下，几乎所有的DC会同时被激活。这可能发生在败血症（血液中的细菌感染）和疟疾期间。人们很早就认识到这两种情况会抑制免疫系统它们会关闭免疫系统。我们之前的工作已经证明，这部分是由于败血症或疟疾激活的DC数量过多，导致没有更多的DC能够对随后的感染做出反应。这项工作的重点是败血症或疟疾的直接影响——在最初的24小时左右；现在我们要研究这些条件对直流网络重构的影响。我们认为，这将有助于我们找到恢复免疫能力的治疗方法——在败血症或疟疾患者中恢复免疫系统的功能。

The immune system fights viruses and other infections mobilising antibody-producing B cells and killer T cells. The B cells and killer T cells are recruited by specialysed cell of the immune system called Dendritic Cells (DC). The DC are distributed all over the body, where they play an immunosurveillance role: they constantly monitor their sorroundings for the presence of pathogens. When DC detect these pathogens they become activated . They capture the pathogen, break it into small pieces called antigens, and display these antigens on their surface, where they can be seen by helper T cells, which in turn mobilise the B cells, and by killer T cells. This chain of reactions initiates an immune response. The DC undergo profound changes after they detect pathogens. They stop monitoring their sorroundings, and concentrate on displaying to T cells the antigens that belonged to the pathogen that triggered their initial activation. Indeed, they do not respond to new pathogen encounters. In normal conditions few DC are activated by each pathogen encounter, so there are always enough DC ready to respond to new infections. However, there are situation that activate nearly all the DC at the same time. This can happen during sepsis (bacterial infection of the blood) and malaria. It has been recognised for a long time that these two conditions can be immunosuppressive they shut-down the immune system. Our previous work has demonstrated that this is in part due to the excessive number of DC that sepsis or malaria activate, leaving no more DC capable of responding to subsequent infections. This work has focused on the immediate effects of sepsis or malaria -within the first 24 hours or so; now we want to investigate the efffect of these conditions on the reconstitution of the DC network. We think this will help us to find treatments to restore immunocompetence a functional immune system- in sepsis or malaria patients.