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

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

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

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

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

Characteristics of Cytokine Function Pleiotropy Redundancy Antagonism Synergy

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

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

（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.

（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.

（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.

（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.

（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.

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

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

Section 4 Biological Activities of Cytokines

（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

（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

（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.

（4）Stimulate Hematogenesis GM-CSF, M-CSF, G-CSF IL-7, EPO IL-6, IL-11, TPO

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

Section 5 Biological Products Derived From Cytokines and Their Receptors

（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)

（2）Cytokines are related to therapeutics of diseases Treatment of tumor and immunodeficiency, Fight against viral infection, Stimulation of hematogenesis

（3）Cytokines are related to other responses Inhibit graft rejection Hypocytosis Hypersensitivity Autoimmune disease

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

Section 1 Functional molecule on immunocyte surface and human leukocyte differentiation antigen Electronic microscope image of human T lymphocyte

（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

（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.

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

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

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.

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.

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.

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

（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

（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

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

Adhesion of leukocyte and vascular endothelial cell during the inflammation

Homing of Lymphocyte

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

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