医学免疫学课件：7 CD CAM

1、Leukocyte Differentiation Antigens Cell Adhesion Molecules,Contents,Concept of leukocyte differentiation antigens （白细胞分化抗原） Concept of cluster of differentiation （CD分子，分化群） Cell adhesion molecules,Leukocyte differentiation antigens,Leukocyte differentiation antigens: Cell surface molecules which may

2、 appear or disappear from the cell membrane of leukocytes in the different stages of differentiation and activation. （第6版p58） Leukocyte differentiation antigens are also found on cells other than leukocytes, such as erythrocytes, endothelial cells, epithelial cells.,Immunoglobulin superfamily Cytoki

3、ne receptor family C-Type lectin superfamily Integrin family TNF superfamily TNF receptor superfamily,Classification of LDA,Cluster of differentiation (CD): Cell surface molecules can be recognized by particular monoclonal antibodies. All of the monoclonal antibodies that react with a particular mem

4、brane molecule are grouped together as a cluster of differentiation (CD). Each new mAb that recognizes a cell surface molecule is analyzed for whether it falls into a recognized CD designation; if not, it is given a new CD designation that reflects a new membrane molecule. CD1CD363, up to 363 most r

5、ecently (as of 2010) in human,A Cluster of mAbs recognize one Molecule = 1 CD,CD3,BC3,JXT3,2GV6,UCHT1,OKT3 .,RIV7,SP35,C1805,CD4,OKT4,Cluster,Cluster,Clusters,Human CD,Groups CD（example） Adhesion molecules CD11a-CD11c、CD15、CD15s(sLx)、CD18 、 CD29 、CD49aCD49f、CD54(ICAM-1)、 CD62E、CD62L 、CD324(E-cadheri

6、n)、 CD325(N-cadherin)、CD326(EpCAM) Cytokine/ CD25(IL-2R)、CD95(Fas)、CD116-CDw137、CD178(FasL)、 Chemokine receptors CD183(CXCR3)、CD184(CXCR4)、CD195(CCR5)、 CD261CD264(TRAIL-R1TRAIL-R4) Endothelia CD105(TGF-RIII)、CD106(VCAM-1)、CD140(PDGFR)、 CD144、CD299(DCSIGN-related)、 CD309(VEGFR2)、JAM1(CD321)、JAM2(CD32

7、2) Carbohydrate structures CD15u、CD60aCD60c、CD75、CDw327CDw329 Dendritic cells CD80,CD86,CD85 Stem cells CD133、CD243 Erythrocytes CD233CD242 Stromal cells CD331-334 （FGFR1-FGFR4）,The CD system is commonly used as cell markers,CD8,cytotoxic,Cell types and subtypes defined by CDs,B cell T cell CD4+ T c

8、ell Tregs (CD4+CD25+),Rules for assigning a CD number,at least one Workshopcharacterized antibody and good molecular data. the antigen is expressed on the surface of cells involved in immune reactions. the antibodies react with primary cells (not just transfectant or recombinant protein). the antibo

9、dy is available.,CD acts as Receptors or Ligands. Initiates a signal cascade, altering the behavior of the cell, or has other functions, such as cell adhesion.,Functions of CDs Mediate cell-cell interaction: Homing, activation, effecter functions,Functions of CDs 2. Receptors recognize exogenous or

10、soluble substance: pathogens, antibodies, cytokines,CDs related to T cell activation,TCR signaling,CD4 and CD8,function,transmembrane glycoprotein co-receptor of T cell,*CD4: first and second domains bind to nonpolymorphic region of MHC molecules * CD8: IgV-like domain of chain binds to nonpolymorph

11、ic 3 region of MHCmolecules,*for cell adhesion *Involved in TCR-CD3 signal transduction,APC,T细胞,Structure of CD4,Structure of CD8,CCR5,1.CD4 is a primary receptor used by HIV-1 to gain entry into host T cells. 2.HIV-1 attaches to CD4 with a protein in its viral envelope known as gp120. The binding t

12、o CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to other surface receptors on the host cell, the chemokine receptors CCR5 .Following a structural change in another viral protein (gp41), HIV inserts a into the host cell that allows the outer membrane of the virus to fuse wit

13、h the cell membrane. 3.HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors. Therefore, medical professionals refer to the CD4 count to decide when to begin treatment for HIV-infected patients. Normal blood values are 500-1200 x106/L.,CD40 and CD40L (CD154

14、),BCR complex,co-receptor,CDs related to B cell activation,CD79 /CD79 ,Heterodimer cytoplasmic domains contain ITAM. Function: 1. transfers the signals that lead to B cell activation. 2. transports the Ig,BCR signaling,CD19/CD21/CD81,CD19/CD21/CD81 interactions with complement associated with antige

15、n play a role in antigen-induced B-cell activation. CD21=CR2, C3dR, EBV R,CDs constituting FcR family,Different types of human Fc receptors,Role of FcRI (CD64) in the Ab-mediated opsonization of microbes,Role of FcRIII (CD16) and FcRI in ADCC(antibody-dependent cell-mediated cytotoxicity),Cell adhes

16、ion molecules, CAM,A group of proteins involved in adhesion between cells or between cells and extracellular matrix (ECM),CAMs and CD molecules are respectively designated according to the different aspects of these molecules. CAMs are grouped depending on their adhesion functions. CD molecules cont

17、ain the majority of CAMs that have obtained CD designation. A minority of CAMs have not been given CD designation.,Categories of CAM,1. IgSF (immunoglobulin superfamily) 2. Integrin family 3. Selectin family 4. Cadherin family 5. Others: CD44,Integrin,Integrin family is so named because the molecule

18、s of this family primarily mediate the cellular adherence to extracellular matrix, enabling cells and extracellular matrix to form the integration.,Structure: Heterodimeric proteins consisting of two non-covalently bound polypeptides ( chain 1 out of 18, and chain 1 out of 8).,Components of integrin

19、 family 1: VLA (very late activation antigen, 12 members), ligand: VCAM-1(vascular cell adhsion molecule-1) T cell activation (co-stimulation and adhesion) 2: LFA-1 (CD11a,lymphocyte function associated antigen-1, 4 members);Mac-1(CD11b) ligand: ICAM-1(intercellular adhesion molecule-1) T cell activ

20、ation, circulation, inflammation 3: gpIIb ligand:Fg (fibrinogen) Platelet aggregation Distribution Broad distribution on the surface of cells.,Selectin family includes L-selectin, P-selectin and E-selectin, which play important roles in leukocyte adhesion to endothelium, inflammation and lymphocyte

21、homing.,Selectin family,1. Structure Transmembrane glycoproteins, with a number of extracellular domains homologous to those seen in complement control proteins (CCP). The extracellular region also contains a domain related to the EGF receptor and a distal C type lectin-like domain. 2. Members of se

22、lectin family L-selectin: leukocytes (Cd62L) P-selectin: platelets and megakaryocytes (Cd62P) E-selectin: activated endothelia (Cd62E) 3. Ligand: carbohydrates, such as CD15s,Functions of CAM,1. Serving as co-receptors and providing co-stimulatory signals in immune cells recognition and activation C

23、D4/CD8 -MHC II/I (coreceptor) CD28 -B7 (costimulation) 2. Adhesion between leukocytes and vascular endothelial cells in inflammation 3. Lymphocyte homing and recirculation,The sequence of events in the migration of blood leukocytes to sites of infection. Selectins mediate weak tethering and rolling

24、of blood neutrophils on the endothelium; integrins mediate firm adhesion of neutrophils to the endothelium, and chemokines activate the neutrophils and stimulate their migration through the endothelium to the sites of infection.,Role of CAMs in migration of nave and effector T cells. Nave T cells ho

25、me to lymph node as a result of L-selectin binding to its ligand on HEVs(high-endothelial venules), which are present only in lymph nodes. Activated T cells home to sites of infection in peripheral tissues, and this migration is mediated by E-selectin, P-selectin and integrins.,Leucocytes adhesion t

26、o blood vessel,Application of CD, CAM and Their mAb,1. Elucidation of pathogenesis CD4 and AIDS, gp120 binds to CD4 2. Application in diagnosis leukemia, AIDS (ratio of CD4+ to CD8+ T cells) 3. Prophylactic and Therapeutic application Graft rejection: Anti-CD3, Anti-CD25 non-Hodgkins lymphoma: Anti-CD20,Natural Killer cells,3rd lineage of lymphocytes Function in innate immunity to protect against viruses, bac