Multicellular organisms suffer injury and serve as hosts for microorganisms. Therefore, they require mechanisms to detect injury and to distinguish the self from the non-self and the harmless non-self (microbial mutualists and commensals) from the detrimental non-self (pathogens). Danger signals are “damage-associated molecular patterns” (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells. Seemingly ubiquitous DAMPs are extracellular ATP or extracellular DNA, fragmented cell walls or extracellular matrices, and many other types of delocalized molecules and fragments of macromolecules that are released when pre-existing precursors come into contact with enzymes from which they are separated in the intact cell. Any kind of these DAMPs enable damaged-self recognition, inform the host on tissue disruption, initiate processes aimed at restoring homeostasis, such as sealing the wound, and prepare the adjacent tissues for the perception of invaders. In mammals, antigen-processing and -presenting cells such as dendritic cells mature to immunostimulatory cells after the perception of DAMPs, prime naïve T-cells and elicit a specific adaptive T-/B-cell immune response. We discuss molecules that serve as DAMPs in multiple organisms and their perception by pattern recognition receptors (PRRs). Ca2+-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life. Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.
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机译:多细胞生物受到伤害并充当微生物的宿主。因此,他们需要机制来检测伤害,并将自我与非自我区别开来,并将无害的非自我(微生物共生主义和共鸣)与有害的非自我(病原体)区分开。危险信号是“破坏相关分子模式”(DAMP),它从破裂的宿主组织中释放出来或暴露在压力细胞上。似乎普遍存在的DAMP是细胞外ATP或细胞外DNA,片段化的细胞壁或细胞外基质,以及许多其他类型的离域分子和大分子片段,它们在预先存在的前体与完整细胞中分离出的酶接触时释放。这些DAMP中的任何一种都可以使受损的自我识别,通知宿主组织破裂,启动旨在恢复体内平衡的过程(例如密封伤口),并准备邻近组织以感知入侵者。在哺乳动物中,抗原处理和呈递细胞(例如树突状细胞)在感知到DAMPs,初次免疫的T细胞并引发特异性的适应性T- / B细胞免疫反应后成熟为免疫刺激细胞。我们讨论了在多种生物中充当DAMP的分子及其通过模式识别受体(PRR)的感知。 Ca 2 + sup>通量,膜去极化,活性氧的释放以及有丝分裂原激活的蛋白激酶(MAPK)信号级联反应是遍及全树的生物中PRR下游起作用的普遍分子机制。生活。受损自我识别包含同源和类似元素,并且可能在所有真核生物界都已经进化,因为所有生物都为同一问题找到了相同的解决方案:必须识别损害而不必依赖于敌人衍生的分子和对非人类分子的反应自我必须专门针对有害的入侵者。
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