Presentation on theme: "Cytokines 1. Introduction of cytokines 2. Classification of cytokines"— Presentation transcript:
1Cytokines 1. Introduction of cytokines 2. Classification of cytokines 3. Cytokine receptors4. Biological activities of cytokines5. Biological products derived fromcytokines and their receptors
2Section 1 Introduction of Cytokines 1961 Bloom Lymphocytes could secrete some solublemolecules that are not immunoglobulins1969 Dumonde Lymphokine, LK; Monokine, MK1977 Cohen Cytokine, CK1979 IUIS Interleukine, IL
3CytokinesLow-molecular-weight proteins secreted by various types of cells and exerting biological activities through binding to cognate receptors on cell surfaceLow-molecular-weight peptides secreted by activated immune cells as well as stromal cells and possessing biological functions
4（1）Denomination of Cytokines monokinelymphokinecolony stimulating factor，CSFinterleukin，ILinterferon，IFNtumor necrosis factor, TNFgrowth factor，GFchemokine
5（2）The Action Mode and Characteristics of Cytokine Function ParacrineAutocrineEndocrine
8Characteristics of Cytokine Function PleiotropyRedundancyAntagonismSynergy
9Common Properties of Cytokines Physico-chemical property：low molecular weight,glycoprotein of secreting type，monomer form in the majority2. Secreting protein: autocrine，paracrine，endocrine3. Transient and self-restricted synthesis：signalling→transcription→expression→secretion4. Multiple sources：species and status of cells，types of CKs5. Network：display effects combined with other CKs6. High performance：mediated by receptors，high affinity7. Non-specificity：without specific binding of Ag, Ab or MHC
11（1）InterleukinThe term Inerleukin originally refers to cytokines that are produced by one leukocyte and act on another leukocyte.It can be produced by other cells, and act on cells of other types.31 kinds of interleukins have been found, denoted IL-1 ~ IL-31.
12（2）InterferonIt is the first discovered cytokine, designated as IFN based on its capability of interfering infection and replication of viruses.It is divided into three types, including , and .IFN- and IFN- together as type I IFN are mainly produced by plasmacytoid dendritic cells as well as cells with virus infection.IFN-, referred to as type II IFN, is principally secreted by activated T cells and NK cells.
13（3）Tumor Necrosis Factor TNF is a molecule found in 1975, which can lead to hemorrhage and necrosis in the tumor.Its family consists of 18 members, such as TNF-, CD40L and FasL.
14（4）Colony Stimulating Factor It is the factor that is able to stimulate the proliferation and differentiation of multipotent hemopoietic stem cells and hemopoietic progenitor cells in different development stages and form cell colony in semisolid culture.CSF includes GM-CSF, G-CSF, EPO, SCF, TPO and so on.
15（5）ChemokineChemokines constitute a protein family, whose molecular weight is generally between 8 and 10kDa.Their chief function are to recruit monocytes, neutrophils and lymphocytes from blood into infection sites.Based on the number and positioning of cysteine, chemokines are subclassified into 4 groups, CC, CXC, C and CX3C group.
21（1）Antimicrobial Effect IL-1：activate vascular endothelial cellsTNF-：increase permeability of blood vesselIL-6：activate lymphocytes, enhance production of antibodyIL-8：recruit neutrophils and T lymphocytes into sites of infectionIL-12: activate NK cells, promote differentiation of Th1 cells
23（2）Antiviral EffectIFN- and IFN-：make antiviral proteinase produced in cells, stimulate expression of MHC I molecule on the surface of cells with virus infectionIFN-： stimulate expression of MHC I molecule on the surface of cells with virus infection, promote virus-infected cell death mediated by CTL, enhance activity of NK cell
25（3）Regulate Specific Immune Response Recognition and activation stage: some cytokines can stimulate proliferation of immune cells.Effect stage: several cytokines are able to stimulate immune cells to eliminate antigenic material.Under certain conditions, a few cytokines exhibit suppressive activities in immune system.
34Section 5 Biological Products Derived From Cytokines and Their Receptors
35（1）Cytokines are related to pathogenesis of diseases 1.Cytokine and tumor：promote tumor growth (IL-1)kill tumor cells (TNF)2.Cytokine and infection：aggravate infection (IL-1,TNF)anti-infection (IFN)3.Cytokine and autoimmune disease: activate lymphocytes,proinflammation4.Cytokine and hypersensitivity：favor IgE production,5.Cytokine and graft rejection：TNF, IFN, IL-1/26.Cytokine and other disease: hypocytosis (IL-3),acute hepatic necrosis (TNF)
36（2）Cytokines are related to therapeutics of diseases Treatment of tumor and immunodeficiency,Fight against viral infection,Stimulation of hematogenesis
37（3）Cytokines are related to other responses Inhibit graft rejectionHypocytosisHypersensitivityAutoimmune disease
38Leukocyte Differentiation Antigen and Adhesion Molecule1. Functional molecule on immunocyte surface and human leukocyte differentiation antigen2. Adhesion molecule3. Clinical application of CD and adhesion molecule as well as their monoclonal antibody
39Section 1 Functional molecule on immunocyte surface and human leukocyte differentiation antigen Electronic microscope image of human T lymphocyte
40（1） Functional Molecule On Immunocyte Surface Specific antigen-recognition receptorPattern recognition receptorCytokine receptorComplement receptorNK cell receptorIg Fc receptorReceptorsMHC moleculeCo-stimulation moleculeAdhesion molecule
41（2）Definition of Human Leukocyte Differentiation Antigen (LDA) LDA are referred to as the former and present marker molecules on cell surface in the differentiation into different lineages, different stages and activation in blood cells.
42Expressed on leukocyte, erythroid lineage and megakaryocyte/thrombocyte lineage Other non-hematopoietic cellsTransmembrane protein or glycoproteinSome are anchored on plasma membrane with GPI conjuction
43Classification of LDA： Immunoglobulin superfamilyCytokine receptor familyType C lectin superfamilyIntegrin familyTNF superfamilyTNF receptor superfamily
44Cluster of Differentiation, CD： Identified mainly by monoclonal antibody (mAb), one LDA, which is recognized by mAb from different labs and whose coding gene and expression profile have been identified, can be designated CD.
47Section 2 Adhesion Molecule Cell Adhesion Molecule, CAMMolecules that mediate cell-cell or cell-matrix interaction and binding are transmembrane glycoproteins in the majority.
48The denomination of adhesion molecule and CD molecule is based on different aspects. Adhesion molecules are classified by adhesive function.Most adhesion molecules possess a CD number, however, some do not.
49Based on structural features integrin familyselectin familyimmnoglobulin superfamilymucin-like vascular addressincadherin family
50（1）Integrin Family Mediate adhesion of cell and extracellular matrix Elementary structure: heterodimer of , chain14 kinds of subunits, 8 kinds of subunitsExpressed extensively
51（2）Selectin FamilyMediate adhesion of leukocyte and endotheliocyte, occurance of inflammation and homing of lymphocyteElementary structure: transmembrane moleculeL-, P-, E-selectinLigands: oligosaccharyl
57Section 3 Clinical Application of CD and Adhesion Molecule as well as Their Monoclonal Antibody （1）elucidate pathogenesis（2）application in diagnosis（3）application in disease prevention and treatment
58Master the definition, classification, common properties and functions of cytokinesMaster the concept of LDA, CD and adhesion moleculeMaster CD molecules related to recognition and activationof T/B cellBe familiar with cytokines that regulate T/B cell functionComprehend the relationship of cytokines and diseasesComprehend Ig Fc receptor and its biological featuresComprehend classification, features and functionsof adhesion moleculesComprehend clinical applications of CD molecule, adhesionmolecule and their monoclonal antibody