Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed phase, where 30% of patients die due to secondary infection. Deficits in the adaptive immune response may play a major role in sepsis patient mortality. The adaptive immune response involves a number of cell types including T cells, B cells and dendritic cells, all with immunoregulatory roles aimed at limiting damage and returning immune homeostasis after infection or insult. However, in sepsis, adaptive immune cells experience cell death or exhaustion, meaning that they have defective effector and memory responses ultimately resulting in an ineffective or suppressed immune defence. CD4+ T cells seem to be the most susceptible to cell death during sepsis and have ensuing defective secretory profiles and functions. Regulatory T cells seem to evade apoptosis and contribute to the immune suppression observed with sepsis. Preclinical studies have identified a number of new targets for therapy in sepsis including anti-apoptotic agents and monoclonal antibodies aimed at reducing cell death, exhaustion and maintaining/restoring adaptive immune cell functions. While early phase clinical trials have demonstrated safety and encouraging signals for biologic effect, larger scale clinical trial testing is required to determine whether these strategies will prove effective in improving outcomes from sepsis.

中文翻译：

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适应性免疫反应在脓毒症中的作用

脓毒症是一种多重要器官休克和功能障碍的综合征，由对感染的免疫反应不受控制引起，死亡率很高。脓毒症没有治疗方法，它已成为全球关注的问题。现在，患者护理和管理的进步意味着大多数患者在脓毒症的初始高炎症阶段存活下来，但会进展到后来的免疫抑制阶段，其中 30% 的患者因继发感染而死亡。适应性免疫反应的缺陷可能在脓毒症患者的死亡率中起主要作用。适应性免疫反应涉及多种细胞类型，包括 T 细胞、B 细胞和树突状细胞，所有这些细胞类型都具有免疫调节作用，旨在限制损伤并在感染或损伤后恢复免疫稳态。然而，在败血症中，适应性免疫细胞会经历细胞死亡或衰竭，这意味着它们的效应子和记忆反应有缺陷，最终导致免疫防御无效或受到抑制。CD4+ T 细胞似乎是脓毒症期间最容易发生细胞死亡的细胞，并且随后具有缺陷的分泌特征和功能。调节性 T 细胞似乎可以逃避细胞凋亡，并有助于在脓毒症中观察到的免疫抑制。临床前研究已经确定了许多治疗脓毒症的新靶点，包括旨在减少细胞死亡、衰竭和维持/恢复适应性免疫细胞功能的抗凋亡剂和单克隆抗体。虽然早期临床试验已经证明了生物效应的安全性和令人鼓舞的信号，