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LDA and Adhesion molecule

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1 LDA and Adhesion molecule

2 LDA,CD,CAM Functional molecule and human leukocyte differentiation antigen on immunocyte surface 3. Clinical application of CD and adhesion molecule as well as their monoclonal antibody

3 Cell Surface Molecules
Leukocyte differentiation antigen(LDA) :The cell surface markers which express or disappear on the different leukocytes in the different stage of differentiation and activation.

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

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

6 Cell Surface Molecules
CD (cluster of differentiation) : Cell surface molecules of leucocytes that are distinguishable with monoclonal antibodies as an immunologic marker. HCDM(Human cell differentiation molecules)

7 Cell Surface Molecules and HLDA
Surface Molecules of Immune cells Receptors: TCR, BCR, PRR, CKR, CR MHC: MHCⅠⅡ Co-stimulatory Molecules: CD28 Adhesion Molecules: integrin,selectin

8 一、CD molecules of T lymphocytes(p98)

9 1,CD3 Consists of 5 proteins that are designated as , , ,  and .
Three dimers: , ,  () The cytoplasmic domain contains ITAM (immunoreceptor tyrosine-based activation motif) YxxL/V Function: transduction of signals that lead to T cell activation.

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11 2. CD4 and CD8 Coreceptors Involved in MHC-Restricted T Cell Activation Function:CD4 and CD8 are T cell proteins that bind to nonpolymorphic regions of MHC molecules and transduce signals that together with signals delivered by the TCR complex initiate T cell activation. CD4:Receptor of HIV gp120

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13 Structure of CD4

14 Structure of CD8

15 3. CD28 and CTLA-4 CD28: its ligands are B7 family molecules, including B7-1/2 (CD80/CD86) Function: costimulation, activation of T cells CTLA-4(CD152): homodimer, homologous to CD28. Function: inhibits T cell costimulation (the cytoplasmic domain contains ITIM)

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17 4、CD154(CD40L)

18 二、CD molecules of B lymphocytes(p92)

19 1,Ig/Ig (CD79a/CD79b) heterodimer cytoplasmic domains contain ITAM.
Function: 1. transfers the signals that lead to B cell activation. 2. transports the Ig

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21 2. CD19/CD21/CD81/CD225 CD21=CR2, C3dR, EBV R
CD19/CD21/CD81 interactions with complement associated with antigen play a role in antigen-induced B-cell activation. CD21=CR2, C3dR, EBV R

22 Downloaded from: StudentConsult (on 1 June 2006 03:50 PM)
© 2005 Elsevier

23 4,CD40 interacts with CD40L (Th cell)
5,CD80(B7.1), CD86(B7.2) expressed on activated B cells 6,ICAM-1, LFA-1

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25 三、Ig Fc Receptor

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29 Cell adhesion molecules
CAM: A group of proteins involved in adhesion of cell to cell or cell to extra-cellular matrix (ECM), such as ICAM-1, ICAM-2, ICAM-3, VCAM-1 and PECAM etc.

30 Cell adhesion molecules
Cellular recognition, activation, proliferation, differentiation, migration Immune response Inflammation Tumour

31 Cell adhesion molecules
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.

32 Categories of CAM 4. IGSF (Ig superfamily) 5. Mucin-like family
1. Integrin family 2. Selectin family 3. Cadherin 4. IGSF (Ig superfamily) 5. Mucin-like family 6. Others:PNAd, CD44, CD36

33 1, Integrin Family 1)Integrin:Mediate adhesion of cell and extracellular matrix 2)Elementary structure: heterodimer of ,  chain 14 kinds of  subunits, 8 kinds of  subunits

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35 Integrin 3)Integrin family β1: VLA(very late appearing antigen)
β2: LFA-1(lymphocyte function associated antigen-1) ligand:ICAM-1,2,3 β3: gpⅡbⅢa 4)Distribution:Expressed extensively

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37 2、Selectin Family Selectins are carbohydrate-binding proteins present on leukocytes, endothelial cells, and platelets; their principal function is to regulate the migration of leukocytes to various tissues

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39 Functions of CAM 1. As co-receptors and co-stimulating signal in immune cells recognition T cell ← APC: TCR Ag-MHC molecule CD4/CD MHCⅠ/Ⅱ CD B7(CD80/CD86) LFA ICAM-1

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41 2. Adhesion between leukocytes and vascular endothelial cells in inflammation

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44 3. Lymphocyte homing (1) The migration of mature lymphocytes from primary to secondary lymphoid tissues. (2) lymphocyte recirculation (3) The migration of lymphocytes into the inflammatory site. Lymphocyte homing receptor---vascular addressin

45 Downloaded from: StudentConsult (on 1 June 2006 03:50 PM)
© 2005 Elsevier

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47 Application of CD, CAM and Their McAb
1. Investigate the mechanism of diseases CD4 and AIDS CD18 and LAD (Leukocyte adhesion deficiency) 2. Application in diagnosis leukemia, AIDS (ratio of CD4/CD8 T cells) 3. Prophylactic and Therapeutic application Graft rejection: Anti-CD3, Anti-CD25 non-Hodgkin’s lymphoma: Anti-CD20

48 Summary LDA,CD,CAM Function of CD molecules in T cell and B cells
Function of CAM in inflammation and immunity


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