Cytokines(细胞因子)Cytokines are proteins secreted by the cells of innate and adaptive immunity that mediat many of the functions of these cells. Cytokines are produced in response to microbes and other antigens. and different cytokines stimulate diverse responses of cells involved in imminity and inflammation. In the activation phase of adaptive immune responses, cytokines stimulate the growth and differentiation of lymphocytes, and in the effector phases of innate and adaptive immunity, they activate different effector cells to eliminate microbes and other antigens.Cytokincs also activate stimulate the development of hematopoictic cells. In clinical medicine cytokines are important as therapeutic agents and as targets for specific antagonists innumerous immune and inflammatory diseases,细胞因子是由多种细胞产生的,具有调节先天免疫与适应性免疫细胞功能作用的多肽分子。
细胞因子在有微生物和其他抗原作用细胞时产生,不同的细胞因子刺激反应细胞产生不同的反应,其中涉及免疫反应和炎症反应。
免疫反应的反应阶段,细胞因子刺激淋巴细胞的增长与分化;效应阶段,它们激活不同的效应细胞消除细菌和其它抗原。
细胞因子也刺激祖细胞的生长。
在临床医学方面,细胞因子很重要,因为可以作为治疗因子和作为特定免疫和炎性疾病的靶制剂。
The nomenclature of cytokines is often based on their cellular sources. Cytokines that are produced by mononuclear phageocytes were called monokines,and those produced by lymphocytes were called lymphokines.。
With the development of anticytokine antibodies and molecular probes, it became clear that the same protein may be synthesized by lymphocytes,,monocytes,and a variety of tissue cells,,including endothelial cells and some epithelial cells. Therefore, the generic term cytokines is the preferred name for this class of mediators细胞因子是根据其来源细胞而命名的。
由单核细胞产生的细胞因子称为单核因子;由淋巴细胞产生的因子称为淋巴因子。
随着抗细胞因子抗体和分子探针的发展,显然,同种蛋白质可能是由淋巴细胞、单核细胞以及各种组织细胞,包括内皮细胞和某些上皮细胞合成。
因此,通用术语细胞因子是这类介质的首选名字。
General properties of cytokines(细胞因子的一般特性)Cytokincs are polypcpeptides produced in response to microbes and other antigens that mediate and regulate immune and inflammatory reactions. Although cytokinesarc structurally diverse. they share several properties.细胞因子是微生物和其他抗原的刺激诱导细胞产生和调节免疫和炎症反应的可溶性蛋白。
虽然细胞因子的结构不同。
但是他们具有某些共性。
Cytokine secretion is a brief, self-limited event. Cytokines arc not usually stored as preformed molecules. and their synthesis is initiated by new gene transcription as a result of cellular activation. Such transcriptional activation is transient, and the messenger RNA encoding most cytokincs are unstable, so cytokine synthesis is also transient. The production of some cytokincs may additionally be controlled by RNA processing and by post transcriptional mechanisms, such as protcolytic release of an active product from an inactive precursor. Once synthesized, cytokines arc rapidly secreted, resulting in a burst of release as needed细胞因子的分泌是一个短暂的并自我控制的过程。
细胞内无细胞因子前体储存,接受刺激后从激活基因开始至合成、分泌,刺激结束后细胞因子的产生随即停止。
这种转录激活是短暂的,大多数翻译细胞因子的mRNA是不稳定的,因此细胞因子的合成也是短暂的。
某些细胞因子的生产还受翻译水平和转录水平后的调控机制控制,如一个无活性的前体蛋白质水解变成有活性的物质。
细胞因子一旦合成,就会迅速地分泌,根据需要,大量地释放。
The actions of cytokines are often pleiotropie and redundant. Pleiotropis m refers to the ability of one cytokine to act on different cell types.this is property allows a cytokine to mediate diverse biological effects,,but itgreatly limits the therapeutic use of cytokines because administration of a cytokine for a desired clinical effect may result in numerous unwanted side effects. Redundancy refers to the property of multiple cytokines having the same functional effects. Because of this redundancy, antagonists against a single cytokine or mutation of one cytokine gene may not have functional consequences, as other cytokines may compensate细胞因子的作用具有多效性和重叠性。
基因多效性是指一种细胞因子可以作用于不同的细胞类型的能力。
这种性质使一个细胞因子能够介导多样的生物效应,但它极大程度上限制利用细胞因子的治疗手段,因此为得到某种理想的临床效果而使用细胞因子可能导致很多有害的副作用。
重叠性是指多个细胞因子具有相同功能的性质。
正是因为这种性质,拮抗剂对单细胞或突变的细胞因子基因可能不具有作用,其他细胞因子可以弥补。
Cylokines often influence the synthesis and actions of other cytokines. The ability of cytokine to simulate production of others leads to cascades in which a second or third cytokine may mediate the hiological effects of the first. Two cytokines may antagonize each other’s action,-produce additive effects. or, in some cases. produce greater than anticipated.,or synergistic effects,细胞因子经常影响其他细胞因子的合成和作用。
一种细胞因子可以刺激其他细胞因子产生的这种作用,导致第二种或第三种细胞因子迅速合成,以此来调节第一种细胞因子的生物活性。
两个细胞因子之间可能具有拮抗作用,产生副效应,。
或者,在某些情况下。
产生比预期更大的作用,或协同效应, Cytokine actions may be local and systemic. Most cytokines act close to where they are produced either on the same cell that secretes the cytokine (autocrine action) or on a nearby cell (paracrine action). T cells often secrete cytokines at the site of contact with antigen presenting cells, the so-called immune synapse. This may be one reason that cytokines often act on cells in contact with the cytokines producers. When produced in large amounts. ,cytokines may enter the circulation and act at a distance from the site of production (cndocrinaction)细胞因子的作用可能具有局部性和网络性。