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

免疫系统通过动员产生抗体的B细胞和杀伤T细胞来对抗病毒和其他感染。B细胞和杀伤T细胞由免疫系统中被称为树突状细胞(DC)的特殊细胞招募。树突状细胞分布在全身各处，在那里它们扮演着免疫监视的角色：它们不断地监视它们周围的病原体的存在。当DC检测到这些病原体时，它们就会被激活。他们捕获病原体，将其分解成称为抗原的小片段，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，而辅助T细胞反过来又动员B细胞，并被杀手T细胞看到。这一连串的反应会引发免疫反应。DC在检测到病原体后会发生深刻的变化。他们停止监测他们的分选环境，专注于向T细胞展示属于触发它们最初激活的病原体的抗原。事实上，它们对新的病原体遭遇没有反应。在正常情况下，几乎没有DC被每次遇到的病原体激活，所以总是有足够的DC准备好应对新的感染。然而，也存在几乎同时激活所有DC的情况。这可能发生在败血症(血液细菌感染)和疟疾期间。很长一段时间以来，人们已经认识到这两种情况可能会产生免疫抑制作用，它们会关闭免疫系统。我们以前的工作已经证明，这在一定程度上是由于败血症或疟疾激活了过多的DC，没有更多的DC能够应对后续的感染。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；现在我们想要调查这些条件对DC网络重建的影响。我们认为，这将有助于我们找到治疗方法，以恢复败血症或疟疾患者的免疫功能和功能免疫系统。

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.