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TREATMENT

机译:治疗

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摘要

Due to their unique capacity to initiate and regulate adaptive immune responses, dendritic cells (DC) represent the most potent antigen-presenting cells of the immune system. Immature DC reside in peripheral tissues, where they sample and process antigens and efficiently sense a large variety of signals from the surrounding environment. Toll-like receptors (TLR) expressed by DC play a critical role in the detection of invading pathogens as well as in triggering the subsequent immune responses. The differential expression of TLR by different DC subsets may correlate with the induction of different patterns of adaptive immune responses. The rapidly expanding and fundamental knowledge of DC biology furthers promising perspectives for the development of vaccination strategies in different fields. For example, the immunotherapeutic potential of antigen-pulsed DC for the treatment of cancer has been confirmed in a number of experimental tumour models. Furthermore, DC have been shown to serve as natural adjuvants in different models of infectious diseases, mediating protection against various types of pathogens. Using murine leishmaniasis as an example, we have demonstrated that DC, once properly conditioned ex vivo, mediate complete and durable protection against infection. Critical parameters determining the efficiency of DC-based vaccination against microbial pathogens include the origin of DC, the choice of antigen to be used for DC loading, the route of immunization and the state of DC maturation and activation. In the present review, we discuss the necessity to define the mechanisms responsible for the immunostimulatory capacity of DC in vivo, in order to exploit their full potential as vaccination tools.
机译:由于树突状细胞(DC)具有启动和调节适应性免疫反应的独特能力,因此代表了免疫系统中最有效的抗原呈递细胞。未成熟的DC驻留在外周组织中,在那里它们对抗原进行采样和处理,并有效地感测来自周围环境的多种信号。 DC表达的Toll样受体(TLR)在检测入侵的病原体以及触发随后的免疫反应中起关键作用。不同DC子集的TLR的差异表达可能与适应性免疫反应的不同模式的诱导相关。 DC生物学的快速发展和基础知识为不同领域的疫苗接种策略的发展提供了广阔的前景。例如,在许多实验性肿瘤模型中已经证实了抗原脉冲DC治疗癌症的免疫治疗潜力。此外,DC已显示出在不同类型的传染病中充当天然佐剂,介导了针对各种病原体的保护作用。以鼠类利什曼病为例,我们证明了DC,一旦经过适当的离体条件处理,就可以介导完整而持久的感染防护。决定针对微生物病原体的基于DC的疫苗接种效率的关键参数包括DC的来源,用于DC加载的抗原的选择,免疫途径以及DC成熟和激活的状态。在本综述中,我们讨论了定义负责体内DC免疫刺激能力的机制的必要性,以便充分发挥其作为疫苗接种工具的潜力。

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