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细胞因子

时间:2012-11-24 16:07:46    下载该word文档

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. Pleiotropism 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。大多数细胞因子通常以旁分泌或自分泌形式作用于附近细胞或细胞因子产生细胞本身T细胞接触抗原呈现细胞会分泌细胞因子,即免疫突触。这可能是一个原因,细胞因子总是作用于生产细胞因子的细胞。当大规模生产,细胞因子可能进入这个循环并在远离产生处作用(内分泌作用)。

Cytokines initiate their actions by binding to specific membrane receptors on target cells. Receptors for cytokines often hind their ligands with high affinities, with dissociation constants (Kd values) in the range of 10-10 to 10-12mol/1.. (For comparison.,recall that antibodies typically hind antigens with a Kd of 10-1 to 10-11 mol/l, and that major histocompatibility complex (MHC) molecules bind peptides with a Kd of only about 10-6 mol/1..As a consequence. only small quantities of a cytokine are needed to occupy receptors and elicit biological effects. Most cells express low levels of cytokine receptors(on the order 100 to 1000 receptors per cell). but this is adequate for inducing responses.

细胞因子通过结合细胞表面相应的细胞因子受体而发挥生物学作用。细胞因子受体与他们的配体具有高亲和力,分离常数(Kd)范围在10-1to10-12mol/L. .(用于比较,,回想一下,抗体抗原Kd10-1 to 10-11mol/L,组织相溶性(MHC)复合物分子与多肽的Kd仅约为10 6mol/ 1 ) .结果,只有少量的一种细胞因子是需要占据受体和引起的生物效应。大多数细胞表达低水平的细胞因子受体(100年到1000年每个细胞受体)。但这有利于诱导反应。

External signals regulate the expression of cytokine receptors and thus the responsiveness of cells to cytokines. For instance, stimulation of T or B lymphocytes by antigens leads to increased expression of cytokine receptors. For this reason, during an immune response,antigen-specific lymphocytes are the preferential responders to secreted cytokines. This is mechanism for maintaining the specificity of immune responses, even though cytokincs themselves are not antigen specific. Receptor expression is also regulated by cytokines them selves. including the same cytokine that binds to the receptor, permitting positive amplification or negative feedback.

外部信号调节细胞因子受体的表达,以此来对细胞因子的反应。例如,抗原刺激TB淋巴细胞会导致细胞因子受体表达增加。由于这个原因,在免疫反应阶段,特异性淋巴细胞产生特异性细胞因子。这是为了维护特异性免疫反应的机制,即使细胞因子本身不具有抗原特异性。细胞因子受体的表达也调节它们自身的表达。包括相同的细胞因子受体结合,允许积极的放大

或负面的反馈。

The cellular responses to most cytokines consist of changes in gene expression in target cells , resulting in the expression of new functions and sometimes in the proliferation of the target cells. Many of the changes in gene expression induced by cytokines result in differentation of T and B lymphocytes and activation of effector cells such as macrophages. For instance. cytokines stimulate switching of antibody isotypes in B cells, differentiation of helper T cells into THI and TH2 subsets. and activation of microbicidal mechanisms in phagocytes. Exceptions to the rule that cytokines work by changing gene expression patterns are chemokines. which elicit rapid cell migration, and a cytokine called tumor necrosis (TNF). which induces apoptosis by activating cellular enzymes, without new gene scription or protein synthesis.

大多数细胞因子引起靶细胞的基因表达的变化,,导致新功能的表达,有时甚至引起靶细胞的增值。细胞因子引起细胞基因的表达的多种变化,导致B淋巴细胞和T淋巴细胞的分化和细胞受体的激活如巨噬细胞等效应。例如,在B细胞中,细胞因子刺激抗体型别的开关,使辅助性T细胞分化成TH1TH2以及激活巨噬细胞的杀菌机制。趋化因子是个细胞因子作用模式的一个例外,它是通过改变基因的表达。 这引起细胞快速迁移和一个名为肿瘤坏死的细胞因子(TNF)它通过激活细胞凋亡的酶,而没有新基因的转录或者蛋白质的合成。

Functional categories of cytokines细胞因子的功能性种类

cytokines were classified into three main functional categories based on their principal biological actions 细胞因子按照他们的生物活性不同分为三种功能性类别

1.Mediators and regulators of innate immunity are produced mainly by mononuclear phagocytes in response to infectious agents. Bacterial products. such as lipopolysaccharide (LPS). and viral products, such as double-stranded RNA. directly stimulate macrophages to secrete these cytokines as part of innate immunity. The same cytokines may also be secreted by macrophages that are activated by antigen-stimulated T cells (i. e.. as part of adaptive cell-mediated immunity) . Most members of this group of cytokines act on endothelial cells and leukocytes to stimulate the early inflammatory reactions to microbes, and some function to control these responses. NK (natural killer) cells also produce cytokines during innate immune reactions.

1当有侵染性病原体侵染时,单核吞噬细胞就会产生先天性免疫。细菌的产物,如脂多糖(LPS);病毒的产品,如双链RNA。直接刺激巨噬细胞分泌这些细胞因子作为先天免疫的一部分。同样的细胞因子也可能是由抗原刺激的T细胞激活的巨噬细胞产生的,(作为适应性细胞免疫的一部分),这一系列细胞因子中的大多数作用于上皮细胞和白细胞,刺激早期炎症反应来抵抗微生物,以及控制这些反应的一些功能。NK(自然杀手细胞在先天性免疫过程中也产生细胞因子。

2. Mediators and regulators of adaptive immunity are produced mainly by T lymphocytes in response to specific recognition of foreign antigensSome T cell cytokines function primarily to regulate the growth and differentiation of various lymphocyte populations and important roles in the activation phase of T cell-dependent immune responses. Other T cell-derived cytokines recruit,activate, and regulate specialized effector cells, such as mononuclear phagocytes, neutrophils, and eosinophils, to eliminate antigens in the effector phase of adaptive immune responses..

2。适应性免疫的是由T淋巴细胞产生,用来特异性识别外来抗原。一些T细胞产生的细胞因子最主要的作用是 调节不同淋巴细胞种群的增长和分化以及在T细胞免疫反应中具有重要的作用。其他T细胞衍生细胞因子招集、激活,调节特异的效应细胞,如单核吞噬细胞,中性粒细胞,嗜酸性粒细胞,在适应性免疫的效应阶段去消除抗原。

3.Stimulators of hematopoiesis are produced by bone marrow stromal cells, leukocytes and other cells, and stimulate the growth and differentiation of immature leukocytes.

In general, the cytokines of innate and adaptive immunity are produced by different cell populations and act on different target cells. However these distinctions are not absolute because the same cytokine may be produced during innate and adaptive immune reactions, and different cytokines produced during such reactions may have overlapping actions

3。造血细胞因子是由骨髓基质细胞,白细胞以及其他细胞产生,并刺激不成熟的白细胞的增长与分化。

一般来说,先天和后天免疫系统的细胞因子是由不同的细胞种群产生,并作用于不同的靶细胞。然而这些区别不是绝对的,因为相同的细胞因子可能在先天和适应性免疫反应中产生,在这些阶段产生的不同的细胞因子可能具有重叠效应。

Cytokine receptors and signalling细胞因子受体和信号

All cytokine receptors consist of one or more transmemhrane proteins whose extracellular portions are responsible for cytokine binding and whose cytolasmic portions are responsible for initiating intracellular signalling pathways. These signalling pathways are typically activated by ligand-induced receptor clustering, bringing together the cytoplasmic portions of two or more receptor molecules in a process analogous to signalling by T and B cell receptors for antigens.

全部的细胞因子受体都是由一个或多个跨膜蛋白组成,这些蛋白的胞外部分决定着细胞因子的结合而其胞质部分决定着包内信号途径的初始化。这些信号途径通常是由配位体诱导激活受体集群, 在一个过程汇集了胞质部分两个或两个以上的受体分子,这类似于抗原结合TB细胞受体的信号途径

The most widely used classification of cytokine receptors is based on structural homologies among the extracellular cytokine-binding domains. According to this classification. cytokine receptors are divided into five families.

最广泛使用的细胞因子受体的分类是基于细胞因子的胞外结合域的结构性同源性。根据这一分类标准,细胞因子受体分为五个家族。

Type I cytokine receptors, also called hemopoietim receptors, contain one or more copies of a domain with two conserved pairs of cysteine residues and membrane proximal sequence of tryptophan serine X tryptophan serine (WSXWS). where X is and aminoacid. These receptors typically bind cytokine that fold into four a helical strands. The conserved features of the receptors presumable form structure that bind four a helical cytokines,but the specific for individual cytokines is determined by amino acid residues that vary from one receptor to another. These receptors consist of unique ligand-binding chains and one or more signal-transducing chain which are often shared by receptors for different cytokines.

类型1——细胞因子感受器,也称作生血素受体,包含一个或者更多的拥有两对半胱氨酸残基和临近细胞膜的WSXWS序列的域,其中X是任意氨基酸。这些受体被代表性地折叠成4个α螺旋股。受体可能的保守结构特征是由4个α螺旋细胞因子捆绑而成,但是细胞因子的特殊识别信息却因为受体的不同而由氨基酸残基决定。这些受体是由独特的配体结合链和一个或多个被细胞因子受体一起共享的信号传导链组成。

Type lI cytokine receptors are similar to type receptors by virtue of two extracellular domains which conserved cysteines, but type 0 receptors do not contain the WSXWS motif. These receptors consist of one ligand-binding polypeptide chain and signal-transducing chain.

Some cytokine receptors contain cxtracellular immunoglobulin ( ig) domains and

are therefore classified as members'of the Ig superfamily. This group of receptors receptors bind diverse cytokines that signal by different mechanisms.

类型2——细胞因子感受器在功能方面和保存着半胱氨酸的两个细胞外域的模式受体相像。但是类型2受体不包含wsxws基序。这类受体由一个配体结合多肽链和信号转导连。

一些细胞因子受体包含胞外免疫结构域,这些结构域是免疫超家族的一员。这组受体连接不同的细胞因子,这些细胞因子通过不同的机制发送信号。

TNF receptors belong to a family of receptors (some of which are not cytokine recep-tors) with conserved cysteine-rich extracellular domains. On ligand binding., these receptors activate associated intracellular proteins that induce apoptosis or stimulate gene expression, or both

TNF受体属于一个受体家族(其中一些不是细胞因子受体),该家族含有保守的的富含半胱氨酸胞外结构域。在配体结合域,这些受体激活偶联胞内蛋白,引起凋亡或刺激基因表达或两者都有。

Seven-transmembrane a helical receptors are also called serpentine receptors,because their transmembrane domains appear to "snake" back and forth through the membrane, and G protein-coupled receptors, because their signalling pathways involve GTP-binding (G)-proteins. The mammalian genome encodes many such receptors involved in sensing environ-mental stimuli. In the immune system, members of this receptor class mediate rapid and transient responses to a family of cytokines called chemokines.

七次跨膜的α螺旋状受体也被称为蛇形受体,因为他们的跨膜结构域看来似乎像蛇一样穿行于膜内,还有G蛋白偶联受体是由于它们的信号途径涉及GTP-binding Gproteins。哺乳动物的基因组编码许多这样的受体,包括感知环境的刺激,在免疫系统,这类受体家族的成员快速而短暂地调停一个化学因子的细胞因子家族反应。

Cytokinc receptors can also be grouped according to signal transduction pathway theyactivate. Such a grouping will correspond to structural homologies in the cytoplasmic regionsof the signalling chains of the receptors. In many cases, members of a family defined by ex-tracellular domains engage similar signal transduction pathways.

细胞因子受体也可以根据他们激活的信号转导途径分组,这种分组与受体信号链的胞质同源结构域相一致。在许多类别中,被胞外结构域界定的家族成员启动相同的信号转导途径。

Roles of cylokines in innate immunity and inflammation

Different cytokines play key roles in innate immunity to different classes of microbes. In infections by pyogenic extracellular bacteria, macrophages respond to bacterial endotoxins and perhaps to other bacterial products by producing TNF, ll.-1. and chcmokines. TNFand 1L- I act on

vascular endothelium at the site of the infection,to sintroduce the expression of adhesion molecules that promote stable attachment of blood neutrophils and monocytes to the endothelium at this site. C hemokines produced by the macrophages and by endothelial cells stimulate the extravasation of the leukocytes to the infection. where the innate immune reaction is mounted to eliminate the infectious microbes.

细胞因子在先天免疫力和发炎中的作用。

不同的细胞因子在不同类别微生物的先天免疫力中起着关键作用。在被化脓的胞外细菌感染中,巨噬细胞通过产生TNFIL-1和化学因子来应答细菌内毒素或其他细菌产物。肿瘤坏死因子和白细胞介素-1作用于感染位点的的血管内皮组织从而诱导粘附分子的表达,而该表达可促进血液中嗜中性细胞和单核细胞稳定吸附于该位点。由巨噬细胞和内皮细胞产生的趋化因子刺激白血球在感染出溢出,先天免疫反应机制以此消除感染性微生物。

Macrophages also respond to many microbes. including intracellular bacteria and 1,M, producing bacteria. by secreting IL 12. which induces the local production of IFN-y fromNK cells and T lymphocytes. IFN-y then activates the macrophages to destroy phageocytosed microbes. I1: 12 also stimulates the subsequent adaptive immune response and directs it for-ward THI cells. which are the mediators of IL 12 are complemented by 11:12. Cytokine-mediated leukocyte recruitment and activation are responsible for the injury to normal tissues that often accompanies innate immune reactions to infections. These macrophage-derived cytokines. especially TNF. IL-1 . and IL-12. are also responsible for the systemic manifestations of infection. 巨噬细胞也通过分泌IL-12对许多微生物应答,包括胞外细菌和LPS产生的细胞。IL-12引起来自NK细胞和T淋巴细胞的IFN-r的局部分泌,接着IFN-r激活巨噬细胞吞噬被吞噬了的微生物。IL-12也刺激常规的免疫应答导致产生TH1细胞,这种机制也是IL-12的调停者同时也被IL-12补充。细胞因子介导的白血球补充和激活影响到受到创伤的通常组织伴随着先天免疫机制对感染进行应答。这些巨噬细胞引导出的细胞因子,特别是TNFIL-1IL-12也是引起感染系统机制症状的原因。

In viral infection. type I IFN arc secreted by infected cells and macrophages and func-tion to inhibit viral replication and infection. 11.-15 stimulates the expansion of NK cells, and IL 12 enhances the cytolytic activity of NK cells. NK cell-mediated killing of virus-infected cells eliminates the reservoir of infection. 在病毒感染中,1IFN被分泌由感染的细胞和巨噬细胞,它阻止病毒复制和感染,IL-15刺激NK细胞扩张,IL-12增加NK细胞的细胞因子活动,NK细胞杀死病毒感染细胞并减少宿主的感染。

The dominant cytokines produced in response to different microbes account for the nature of the innate immune reactions to these microbes. For instance. the early response to pyogenic bacteria consists mainly of ncutrophils, the response to intracellular bacteria is dominated by activated macrophages, and the response to viruses consists of NK cells in addition to other inflammatory cells. There may be considerable overlap, however. and there varied cellular reactions may be seen to different degrees in many infections. 起主要作用的细胞因子对不同种的使先天免疫系统产生应答反应的微生物应答。例如,对早其化脓细菌的反应主要由中性粒细胞作用,对细胞内的细菌的反应由巨噬细胞主导,而对病毒的作用除了其他的炎症性细胞外还有NK细胞参与。这些作用可能会有大量的重叠,不管怎样,多种应对感染的细胞反应机制可能在不同层级出现。

Roles of T cell cytokines in specialized adaptive immune responses T细胞因子在特定的适应性免疫反应中角色。

The cytokines of adaptive immunity are critical for the development of immune responses and for the activation of effector cell that serves to eliminate microbes and other antigens. Much of s pecialization of adaptive immunity is due to the actions of cytokines, which may be produced by sulipopulations of helper T cells. Different types of microbes stimulate naive CD4+ T cells to differentiate into effector cells that produce distinct sets of cytokines and perform distinct functions. The best defined of these subsets are the TH1 and TH2 cells. Many intracellular microbes ( bacteria and viruses) induce the development of THl cells, which produce IFN-γ, the cytokine that activates phageocytes to destroy intracellular microbes and stimulates the production of opsonizing antibodies that promote more phagocytosis. Hwlminthic parasites, in contrast, stimulate the development of TH2 cells, which produce II.-4 and IL-5. IL-4 enhances production of helminth-specific IgE antibodies, which coat the parasites. and IL-5 activates eosinphils, which hind to the IgE-coated parasites and destroy them. Thus, cytokines are essential for the development and effectiveness of adaptive immune responses.

适应免疫性的细胞因子对免疫反应的发展是关键性的,为了激活能除去微生物和其它抗体的效应细胞。许多适应性免疫的专一性都归功于细胞因子的行为,这可能是由其亚群的帮手T细胞中生产的。不同类型的微生物刺激初始CD4+T细胞区分于效应细胞产生不同种类的细胞因子并执行独特的功能。能充分证明这些子集的是TH1 TH2 细胞。许多胞内微生物(如细菌和病毒)诱导激活TH1细胞产生IFN-γ,这种细胞因子激活噬细胞去摧毁胞内微生物并刺激产生能分泌更多吞噬作用的促调理型抗体。相比之下,寄生虫感染,会刺激TH2细胞产生II.-4 IL-5II.-4提高产生专一抗虫性IgE抗体,并覆盖在寄生虫上,而IL-5激活嗜酸性细胞,与被IgE抗体完全覆盖的寄生虫捆绑式结合,然后消灭他们。因此,细胞因子是适应性免疫反应有效进行的必要。

Summary(总结)

Cytokines are a family of proteins that mediate many of the responses of innate and adaptive immunity. The same cytokines may be produced by many cell types, and individual cytokines often act on diverse cell types. Cytokines are synthesized in response to inflammatory or antigenic stimuli and usually act locally, in an autocrine or paracrine fashion, by binding to high-affinity receptors on target cells. Certain cytokines may be produced in sufficient quantity to circulate and exert endocrine actions. For many cell types, cytokines serve as growth factors.

细胞因子是调节众多先天性和适应性免疫反应的蛋白质中的一员。同一种细胞因子可能由许多种类型的细胞分泌产生,而胞内细胞因子时常扮演区分细胞类型的角色。综合来讲,细胞因子在响应煽动性或反基因的刺激通常是出于本能,按一种自分泌或旁分泌的方式,通过捆绑在目标细胞的高亲和性受体上。某些细胞因子可能产生足够的数量以满足循环与发挥内分泌行动。对于许多细胞类型,细胞因子作为生长因子。

Cytokines mediate their actions by binding with high affinity to receptors belonging to a limited number of structural families. Different cytokines use specialized signaling pathwayssuch as the JAK/STAT pathway.

细胞因子的调节行动通过与属于有限数量的家庭结构的受体进行高亲和力的绑定实现。不同的细胞因子使用专门的信号通路,比如JAK / STAT途径。

The cytokines that mediate innate immunity are produced mainly by activated macrophages and include the following:TNF and IL-1 are mediators of acute inflammatory reactions to microbes; chemokines recruit leukocytes to sites of inflammation; IL-12stimulates production of the macrophage-activating cytokine IFN- γ; type I IFN are antiviral cytokines; and IL-10 is an inhibitor of macrophages. These cytokines function in innate immune responses different classes of microbes.

细胞因子的调节先天免疫主要由激活巨噬细胞产生,包括以下几点: TNFIL-1是急性炎症反应介质的微生物;趋化因子招募白细胞的地点炎症;IL-12刺激生产的巨噬细胞活化细胞因子IFN -γ;IIFN是抗病毒因子;IL - 10是一种抑制剂的巨噬细胞。这些细胞因子在先天免疫反应中的作用取决于不同类型的微生物。

The cytokines that mediate and regulate adaptive immune responses are produced mainly by antigen-stimulated T lymphocytes, and they include the following: IL-2 is the principle T cell growth factor; IL-4 stimulates IgE production and the development of TH2 cells from naive helper T cells; IL-5 activates eosinophils; is an activator of macrophages; and TGFβ inhibits the proliferation of T lymphocytes and the activation of leukocytes.

细胞因子的调节和规范自适应免疫反应主要是通过抗原刺激产生T淋巴细胞,它们包括以下几点: IL-2T细胞生长因子的根源;IL-4刺激IgE从初始的辅助T细胞中生产和开发TH2细胞;IL-5激活嗜酸性粒细胞,IFN-γ是巨噬细胞的活化剂;TGFβ抑制T淋巴细胞的增殖和激活白细胞。

The colony-stimulating factors (CSF) consist of cytokines produced by bone marrow stromal cells, T lymphocytes, and other cells that stimulate the growth of bone marrow progenitors, thereby providing a source of additional inflammatory leukocytes. Several of these (e. g. , stem cell factor and II,-7) play important roles in lymphopoiesis.

由细胞因子构成的细胞集落刺激因子(CSF)由骨髓基质细胞产生,T淋巴细胞,和其他刺激增长的骨髓干细胞, ,从而提供一个额外的炎性白细胞来源。其中的一些(例如: 干细胞因子和IL-7) 在淋巴细胞增殖中扮演重要角色。

Cytokines serve many functions that are critical to host defense against pathogens and provide links between innate and adaptive immunity. Cytokines contribute to the specialization of immune responses by activating different types of effector cells. Cytokines also regulate the magnitude and nature of immune responses by influencing the growth and differentiation of lymphocytes. Finally, cytokines provide important amplification mechanisms that enable small numbers of lymphocytes specific for any one antigen to activate a variety of effector mechanisms to eliminate the antigen.

细胞因子的许多功能对宿主防御病原体和提供天然免疫与适应性免疫之间的联系都是至关重要的。通过激活效应细胞的不同类型的细胞因子有助于免疫反应的专业化。细胞因子也通过影响淋巴细胞的生长和分化来调整免疫反应的程度和性质。最后,细胞因子提供重要的放大机制, 使用少量的淋巴细胞就能对任何一个特定抗原做出反应,激活各种效应机制来消除抗原。

Excessive production or actions of cytokines can lead to pathologic consequences. the administration of cytokines or their inhibitors is a potential approach for modifying biological responses associated with immune and inflammatory diseases.

过度生产或行动的细胞因子可导致病理症状。对细胞因子或其抑制剂给药是一个用来处理相关免疫和炎性疾病类生物反应的潜在的方法。

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