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1、Chapter 5.cytokines(CK)Part I. IntroductionConceptCommon featuresI. concepta group of low molecule weight proteins secreted by activated immunocytes and some matrix cells which bear high activity and different functions.LymphokinesMonokinesColony stimulating factors (CSF)II.Common features of cytoki
2、nes1.Low molecule weight polypeptides or glucoprotein. (60KD) , Most of them are monomer2.One kind cytokine can be produced by different cells.One kind of cells can secrete different cytokinesTH1 IL3,GM-CSF,TNFa TH2 IL-2 IFNr,TNF IL4,6 IL5 TH1TH23.Most of cytokines are secreted by activated cells: a
3、ctivated immune cells,matrix cells and some tumor cells. 4.Cytokines act on target cells by the way of paracrine, autocrine or endocrine.自分泌 autocrine內(nèi)分泌 endocrine血液循環(huán)遠距離作用旁分泌 paracrine作用于比鄰細胞細 胞 因 子 發(fā) 揮 作 用 的 三 種 方 式作用于分泌細胞自身Cytokines can act on the cells that produce them (autocrine action), on ot
4、her cells in the immediate vicinity (paracrine action), or on cells at a distance (endocrine action) after being carried in blood or tissue fluids 5. Cytokines act on target cells by binding to cytokine receptors. 6.bear high activity , multi-effects and form a cytokine network.Cytokines can have ef
5、fect in spite of very low concentration.One kind of cytokine may have mutiplicate effects.(pleiotropy)Several kinds of cytokines may have the same or similar effect. 肥大細胞胸腺細胞BIL-4 多效性pleiotropy活化、增殖、分化增殖增殖IL-2、 IL-4、 IL-5IL-4 + IL-5B細胞IL-4IFN-g 拮抗性antagonism 重疊性redundancy協(xié)同性synergy均有刺激B細胞增殖的功能更有效地誘導
6、IgE類別轉換IL-4 阻斷IFN-g 誘導類別轉化的作用BBBTH1MjIL- 4 骨髓基質細胞IL-1 IL-6 IL-7 SCF 造血干細胞IL-1 IL-6 IL-11 TNF-a GM-CSF G-CMF M-CSF單核細胞TH2B中性粒細胞嗜酸性粒細胞IL-1 IL-8 TNF-aIL-1 TNF-aIL-10 IL- 4IL- 4 IL-6 IL-10 IL-13 IL-4 TGF-bIL-4 IL-5 IL-6 IL-13 IL-10 TGF-bIL-4IL-4內(nèi)皮細胞IL-4TcIL-4IL-2 IFN-gIL-10 IL-13 IL-4 NK1+T NK 細胞IFN-gIL
7、-2IL-2 IFN-gIL-2IL-2 IL-12G-CMF IFN-g GM-CSF IL-12IL-1 TNF-a TGF-b PDGF FGF M-CSF GM-CSF 內(nèi)皮細胞纖維母細胞下 丘 腦IL-1 TNF-aM-CSF GM-CSF IL-1 IL-6 TNF-aIL- 4IL- 6IL- 4Part II. Classification of cytokines and major activitiesI. classificationInterleukin,ILInterferon , IFNColony stimulating factor,CSFTumor necro
8、sis factor, TNFGrowth factorchemokine1.InterleukinesInterleukine, ILs: any membrane of herogeneous group of cytokines secreted by leokocytes that have the ability to act as signaling molecules between different population of leukocytes. IL-1IL-232. Interferons (IFNs): any members of a group of glyco
9、proteins that produced and liberated by human or animal cells following the infection of virus and exposure to a variety of inducing agentsInterferon are involved in defense against viral infection and in activation and modulation of immunity. Comparison of IFN-, IFN-, IFN-_Types produced cells indu
10、cing agents_ IFN- leukocyte virusIFN- fibroblast virus, poly I:CIFN-type II Th1,NK Ag, mitogen_Type IIFN-a 的 抗 病 毒 作 用病毒病毒復制抑制病 毒復制信號轉導IFN-aIFN-誘導蛋白誘導刺激胞核 胞核 3.colony-stimulating factors, CSFany cytokines that control the differentiation of hemopoietic stem cell , both in the bone marrow and in the
11、periphery.Multi-CSF (IL-3) Granulocyte/macrophage-CSF, GM-CSFgranulocyte-CSF, G-CSFmacrophage CSF, M-CSF4.Tumor necrosis factors, TNFs :TNF-, TNFN-TNFs were originally thought of as selective antitumour agents ,but are now known to have a multiplicity of actions.TNF- is produced mainly by monocytes
12、and macrophage .TNF- is produced by lymphoid cells 5. Growth-factor Growth-factor are cytokines which drive the growth of their target cells.6. Chemokine Chemokines are cytokines which direct cell migration and /or activate cells. II. Biological effects of cytokinesTake part in nonspecific immunity
13、-IFN and IFN 2. Take part in specific immunity3. Induce apoptosis4. Stimulate hematopoiesis Part III. CK receptor1. Membrane-binding cytokine receptors: The receptor consists of extra-cellular region, trans-membrane region and cytoplastic region. The cytokine receptors can be grouped by structure into five families :(1) Immunoglobulin family(2) Type I cytokine receptor family(3) Type II cytokine(IFN) receptor family(4) Type III cytokine(TNF) receptor family(5) Chemokine re
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