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Cytokines 1. Introduction of cytokines 2. Classification of cytokines

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1 Cytokines 1. Introduction of cytokines 2. Classification of cytokines
3. Cytokine receptors 4. Biological activities of cytokines 5. Biological products derived from cytokines and their receptors

2 Section 1 Introduction of Cytokines
1961 Bloom Lymphocytes could secrete some soluble molecules that are not immunoglobulins 1969 Dumonde Lymphokine, LK; Monokine, MK 1977 Cohen Cytokine, CK 1979 IUIS Interleukine, IL

3 Cytokines Low-molecular-weight proteins secreted by various types of cells and exerting biological activities through binding to cognate receptors on cell surface Low-molecular-weight peptides secreted by activated immune cells as well as stromal cells and possessing biological functions

4 (1)Denomination of Cytokines
monokine lymphokine colony stimulating factor,CSF interleukin,IL interferon,IFN tumor necrosis factor, TNF growth factor,GF chemokine

5 (2)The Action Mode and Characteristics of Cytokine Function
Paracrine Autocrine Endocrine



8 Characteristics of Cytokine Function
Pleiotropy Redundancy Antagonism Synergy

9 Common Properties of Cytokines
Physico-chemical property:low molecular weight, glycoprotein of secreting type,monomer form in the majority 2. Secreting protein: autocrine,paracrine,endocrine 3. Transient and self-restricted synthesis: signalling→transcription→expression→secretion 4. Multiple sources:species and status of cells,types of CKs 5. Network:display effects combined with other CKs 6. High performance:mediated by receptors,high affinity 7. Non-specificity:without specific binding of Ag, Ab or MHC

10 Section 2 Classification of Cytokines
Interleukin,IL Interferon,IFN Tumor necrosis factor,TNF Colony stimulating factor,CSF Chemokine Growth factor,GF

11 (1)Interleukin The 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)Interferon It 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)Chemokine Chemokines 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.


17 (6)Growth Factor GF is able to stimulate cell growth, including members of TGF-, EGF, VEGF, FGF, NGF and PDGF.

18 Section 3 Cytokine Receptors
Classification of cytokine receptors: Type I cytokine receptor family Type II cytokine receptor family Tumor necrosis factor receptor superfamily Chemokine receptor family


20 Section 4 Biological Activities of Cytokines

21 (1)Antimicrobial Effect
IL-1:activate vascular endothelial cells TNF-:increase permeability of blood vessel IL-6:activate lymphocytes, enhance production of antibody IL-8:recruit neutrophils and T lymphocytes into sites of infection IL-12: activate NK cells, promote differentiation of Th1 cells


23 (2)Antiviral Effect IFN- and IFN-:make antiviral proteinase produced in cells, stimulate expression of MHC I molecule on the surface of cells with virus infection IFN-: 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.



28 (4)Stimulate Hematogenesis




32 (5)Promote Angiogenesis
Several CXC chemokine, IL-8 and FGF can stimulate vasculogenesis.


34 Section 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, proinflammation 4.Cytokine and hypersensitivity:favor IgE production, 5.Cytokine and graft rejection:TNF, IFN, IL-1/2 6.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 rejection Hypocytosis Hypersensitivity Autoimmune disease

38 Leukocyte Differentiation Antigen
and Adhesion Molecule 1. Functional molecule on immunocyte surface and human leukocyte differentiation antigen 2. Adhesion molecule 3. Clinical application of CD and adhesion molecule as well as their monoclonal antibody

39 Section 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 receptor Pattern recognition receptor Cytokine receptor Complement receptor NK cell receptor Ig Fc receptor Receptors MHC molecule Co-stimulation molecule Adhesion 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.

42 Expressed on leukocyte, erythroid lineage and megakaryocyte/thrombocyte lineage
Other non-hematopoietic cells Transmembrane protein or glycoprotein Some are anchored on plasma membrane with GPI conjuction

43 Classification of LDA:
Immunoglobulin superfamily Cytokine receptor family Type C lectin superfamily Integrin family TNF superfamily TNF receptor superfamily

44 Cluster 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.



47 Section 2 Adhesion Molecule
Cell Adhesion Molecule, CAM Molecules that mediate cell-cell or cell-matrix interaction and binding are transmembrane glycoproteins in the majority.

48 The 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.

49 Based on structural features
integrin family selectin family immnoglobulin superfamily mucin-like vascular addressin cadherin family

50 (1)Integrin Family Mediate adhesion of cell and extracellular matrix
Elementary structure: heterodimer of ,  chain 14 kinds of  subunits, 8 kinds of  subunits Expressed extensively

51 (2)Selectin Family Mediate adhesion of leukocyte and endotheliocyte, occurance of inflammation and homing of lymphocyte Elementary structure: transmembrane molecule L-, P-, E-selectin Ligands: oligosaccharyl


53 (3)Function of Adhesion Molecule
Co-receptor and co-stimulation signal in the recognition of immunocyte

54 Adhesion of leukocyte and vascular endothelial cell during the inflammation


56 Homing of Lymphocyte

57 Section 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

58 Master the definition, classification, common properties
and functions of cytokines Master the concept of LDA, CD and adhesion molecule Master CD molecules related to recognition and activation of T/B cell Be familiar with cytokines that regulate T/B cell function Comprehend the relationship of cytokines and diseases Comprehend Ig Fc receptor and its biological features Comprehend classification, features and functions of adhesion molecules Comprehend clinical applications of CD molecule, adhesion molecule and their monoclonal antibody

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