New insights into the biology of the acute phase response
New insights into the biology of the acute phase response
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DOI：
10.1023/a:1020563913045
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发表时间：
1999-07-01
影响因子：
9.1
通讯作者：
O'Grady, NP
中科院分区：
文献类型：
--
作者：
Suffredini, AF;Fantuzzi, G;O'Grady, NP
天然免疫是一种高度保守的防御感染机制，存在于所有多细胞生物体中。急性时相反应是由模式识别分子启动的一组即时炎症反应。这些生殖细胞编码的蛋白质基于共同的分子结构识别微生物病原体，并诱导宿主反应，定位感染的传播，增强系统对感染的抵抗力。先天免疫还通过调节T细胞的共刺激活性和抗原提呈细胞的抗原提呈，影响介质的产生，从而影响淋巴细胞的功能和运输，从而影响获得性免疫反应的启动和类型。急性时相蛋白浓度在感染后迅速增加，其产生主要受IL-6和IL-L类细胞因子的控制。急性期蛋白提供对微生物的增强保护，并通过影响细胞运输和介质释放来改变炎症反应。例如，血清淀粉样蛋白A具有强大的白细胞激活功能，包括诱导趋化、增强白细胞与内皮细胞的黏附和增加吞噬功能。人体注射内毒素后出现的一系列炎症反应代表了急性时相反应的活体模型。对炎症修饰剂，如可溶性二聚体肿瘤坏死因子受体和IL-10的研究表明，这些反应不依赖于单一的介质，而是多条重叠的炎症途径的结果。了解启动和改变急性期反应的大小和持续时间的因素是发展传染病和炎症性疾病新疗法的重要一步。
Innate or natural immunity is a highly conserved defense mechanism against infection found in all multicellular organisms. The acute phase response is the set of immediate inflammatory responses initiated by pattern recognition molecules. These germ cell-encoded proteins recognize microbial pathogens based on shared molecular structures and induce host responses that localize the spread of infection and enhance systemic resistance to infection. Innate immunity also influences the initiation and type of adaptive immune response by regulating T cell costimulatory activity and antigen presentation by antigen presenting cells and by influencing mediator production, which affects lymphocyte function and trafficking. Acute phase protein concentrations rapidly increase after infection, and their production is controlled primarily by IL-6- and IL-l-type cytokines. The acute phase proteins provide enhanced protection against microorganisms and modify inflammatory responses by effects on cell trafficking and mediator release. For example, serum amyloid A has potent leukocyte activating functions including induction of chemotaxis, enhancement of leukocyte adhesion to endothelial cells, and increased phagocytosis. The constellation of inflammatory responses seen after endotoxin administration to humans represents an in vivo model of the acute phase response. Studies with inflammatory modifying agents, such as soluble dimeric TNF receptor and IL-10, show that these responses are not dependent on a single mediator but result from multiple overlapping inflammatory pathways. Understanding the factors that initiate and alter the magnitude and duration of the acute phase response represents an important step in the development of new therapies for infectious and inflammatory diseases.