免疫学课件细胞因子

CytokinesCytokinesXiaojian WangInstitute of Immunology Zhejiang U Cytokines are small soluble proteins that mediate immune and inflammatory reactions and are responsible for communications between leukocytes or between leukocytes and other cells via binding the receptor.是除免疫球蛋白和补体的另一类特异性免疫效应物质 Introduction to cytokinesCytokines work by binding to a target cell.Therefore,for a cytokine to have an effect,two things have to occur:The cytokine needs to be present thereThe target cell needs to have a receptor on its surfaceTherefore,regulation can occur at either step.Nomenclaturen According to their source 1)Lymphokine 2)Monokinen According to their function 1)Colony stimulating factor 2)Interleukin 3)Interferon 4)Tumor necrosis factor 5)Growth factor 6)ChemokineManner of action 1)Autocrine:IL-2 Th Th 2)Paracrine:IL-12 DC Th 3)Endocrine:IL-1,TNF-Under certain circumstances(e.g.septic shock),large amounts of CKs(such as TNF-)are produced,they may be active distant from their site of secretion.Manner of action1.General Properties of Cytokines2.Functional Categories of cytokines3.Cytokine receptors4.Biologic function of Cytokines5.Cytokine related diseases6.Therapeutic Use of cytokinesCytokines1.1.The actions of cytokines are often pleiotropic and redundant;1.2.Cytokines often influence the synthesis and actions of other cytokines;1.General Properties1.3.Cytokine actions may be local and systemic;1.4.Cytokines initiate their actions by binding to specific membrane receptors on target cells;1.5.The cellular responses to most cytokines consist of changes in gene expression in target cells,resulting in the expression of new functional protein in the target cells.One cytokine can target different target cells1.1 The actions of cytokines are often pleiotropic and redundantDifferent cytokines can exert similar effect 1.1 The actions of cytokines are often pleiotropic and redundant Cytokine NetworkCytokines can work together or against each other1.2 Cytokines often influence the actions of and synthesis of other cytokines;One cytokine can induce another cytokine and so on.1.2 Cytokines often influence the actions and the synthesis of other cytokines(Cascade effect)1.3 Cytokine actions may be local and/or systemic 1.4 Cytokines initiate their actions by binding to specific membrane receptors on target cells.1.5 The cellular responses to most cytokines consist of changes in gene expression in target cells,resulting in the expression of new functional protein in the target cellsGeneral Properties1.Pleiotropism2.Redundancy3.Synergy4.Antagonism5.NetworkCKs are classified into 6 functional categories2.1 Interleukines2.2 Interferons2.3 Colony Stimulating Factors2.4 TNF family2.5 Chemokines2.6 Transforming Growth Factors2.Functional Categories of cytokines1.Cytokines produced by leukocytes and act on leukocytes The term interleukine,(inter-)as a means of communication,(-leukin)deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes.2.The interleukins are produced by a wide variety of body cells.The function of the immune system depends in a large part on interleukins,2.1 Interleukins(IL)The majority of interleukins are synthesized by helper CD4+T lymphocytes,as well as through monocytes,macrophages,and endothelial cells.They promote the development and differentiation of T,B,and hematopoietic cells.And rare deficiencies of a number of them have been described,all featuring autoimmune diseases or immune deficiency.Interleukin,ILIL 138 IL-2（T cell growth factor）IL-4（B cell growth factor,Th2 type）IL-6（Th2 type）IL-8（belongs to chemokine）IL-10（Th2 type）IL-11（stimulator of platelet）IL-12（Th2 type）IL-2IL-4Interferons(IFNs)are natural cell-signaling proteins produced by the cells of the immune system to challenges such as viruses,parasites and tumor cells.Groups Type I IFN:IFN-and IFN-The major source is leukocytes(PDC),fibroblasts and virus infected cells.Help prevent the spread of virus to uninfected cells.Type II IFN:IFN-IFN-is produced by activated T cells and NK cells.Its main function is immune regulation.2.2 Interferons(IFNs)IFN-的 抗 病 毒 作 用病毒病毒病毒复制病毒复制抑制病抑制病 毒复制毒复制信号信号转导IFN-IFN-诱导蛋白蛋白诱导刺激刺激胞核胞核 胞核胞核 2.3 Colony-stimulating factorColony-stimulating factors(CSFs)are secreted glycoproteins which bind to receptor proteins on the surfaces of hemopoietic stem cells and thereby activate intracellular signaling pathways which can cause the cells to proliferate and differentiate into a specific kind of blood cell(usually white blood cells）。The name“colony-stimulating factors”comes from the method by which they were discovered.Hemopoietic stem cells were cultured in semi solid matrix which prevents cells from moving around,so that if a single cell starts proliferating,all of the cells derived from it will remain clustered around the spot in the matrix where the first cell was originally located,and these are referred to as colonies.It was therefore possible to add various substances to cultures of