1 Chapter 7 CAM & LDA Department of Immunology Xing-cheng WEI ( 韦星呈 ) Building of Basic Medicine Room 323 Tel (office)

2  Cell Adhesion Molecules  Leukocyte Differentiation Antigen  Clinical application of CAM and CD

3 Sec.1 CAM

4 Concept: Concept: The Molecules mediating contact and binding between cell and cell or between cells and extracellular matrix. The Molecules mediating contact and binding between cell and cell or between cells and extracellular matrix. CAM (cell adhesion molecule)

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7 Double Signals & Accessory Molecules

8 Families of CAM -To be grouped according to molecular -To be grouped according to molecular structures and biological features. 1. Integrin 1. Integrin 2. Selectin 2. Selectin 3. IgSF 3. IgSF 4. Cadherin family 4. Cadherin family 5. Non-classified molecules 5. Non-classified molecules

9 Double Signals & Accessory Molecules

10 I. Integrin -making cells adhere to extra-cellular matrix as to form an integration. heterodimer a and b chains ﹥ 14 a chains  8  chains (group)

11 Members of Integrin Family (1) Groups Members a/b Subunit MW (KDa) Subunit structure Distribution Ligands Binding domains VLA （  1 Group ） Melanoma

12 Groups Members a/b Subunit MW (KDa) Subunit structure Distribution Ligands Binding domains Continued Leukocyte adhesion receptor （  2 Group ） Platelet glycoproteins （  3 Group ） Members of Integrin Family (2)

13 Groups Members a/b Subunit MW (KDa) Subunit structure Distribution Ligands Binding domains  4 group  5 group  6 group  7 group  8 group Members of Integrin Family (3) Continued

14 Integrin molecules adhesion to extracellular matrix

15 Integrin molecules adhesion to the ligands on endothelial cells

16 APC T Cell Integrin molecules adhesion to the ligands on APC

17 II. Selectin By adhesion leukocyte-endothelium, a selectin takes part in leukocyte mediated inflammation and lymphocyte homing. General Structure

18 --L-selectin --E-selectin --P-selectin sialyl-Lweis X (sLeX, or CD15s) Selectin family & the Ligands Common ligand:

19 Members of Selectin Family SelectinsDistributionLigandsFunctions L-Selectin (CD62L) Leucocytes CD15s(sLe x ) DC34 GlyCAM-1 Adhesion of leukocyte- endothelium Lymphocyte homing P-Selectin (CD62P) Platelets Megakaryocytes Activated endothelia CD15s(sLe x ) PSGL-1 Adhesion of leukocyte- endothelium Adhesion of leukocyte- platelet E-Selectin (CD62E) Activated endothelia CD15s(sLe x ) PSGL-1 Myeloid cells CLA ESL-1 Adhesion of leukocyte- endothelium Migration of leukocyte to tissue Metastasis of tumor cell

20 Selectin molecule adhesion to the ligand on endothelial cell

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22 III. IgSF -A great number of members. -Possessing ≥1 Ig domain. -Mediate cellular adhesion to offer stimulating signals for the cells.

23 [Review] Domain of Ig Structure of IgG revealed by X-ray crystallography [Ig folding] -A globular motif. -2 Anti-parallel  sheet. - ～ 110AA. - IgSF : any molecule that contains ≥ 1 Ig folding domain.

24 APC T Cell IgSF molecules Bind to the ligands During T cell activation

25 Members of IgSF (1) T cell activation Distribution LigandsFunctionsIgSF Molecules Cell adhesion Th co-receptor, HIV receptor Tc co-receptor Accessory signals for T activation T cell inactivation Accessory signals for T activation / inactivation Accessory signals for T activation / inactivation Cell adhesion widespread

26 Lymphocyte adhesion, activation, co-stimulation IgSF Molecules Distribution LigandsFunctions Cell adhesion, activation, adhesion, killing Cell adhesion, killing Cell adhesion, killing; Junction of endothelia Lymphocyte homing Cell adhesion; Junction of endothelia Cell adhesion Unknown Members of IgSF (2)

27 Some IgSF Molecules （ T Cells ）

28 Some IgSF Molecules （ B Cells ）

29 Some IgSF Molecules （ Ig FcR ）

30 IV. Functions of CAM

31 Functions of CAM 1. Co-receptors & accessory 1. Co-receptors & accessory molecules for activation of molecules for activation of T and B cells. T and B cells. 2. Interaction of leukocytes 2. Interaction of leukocytes with vascular endothelium with vascular endothelium in inflammation reactions. in inflammation reactions. 3. Interaction of lymphocytes 3. Interaction of lymphocytes with vascular endothelium with vascular endothelium in Lymphocyte homing. in Lymphocyte homing. Entering Non-lymphoid Tissues Entering Lymphoid Tissues

32 Co-Receptors & Accessory Molecules for T & B Cell Activation APC T Cell -Receptor: -Receptor: TCR TCR -Co-Receptor: -Co-Receptor: CD4,CD8 CD4,CD8 -Accessory Mol: -Accessory Mol: CD28,CD2,etc CD28,CD2,etc

33 Interaction of Immune Cell with Vascular Endothelium in Inflammation or Lymphocyte Homing

34 Sec.2 LDA

35 LDA Leukocyte differentiation antigen Distribution: -Leucocytes. -Leucocytes. -Non-hemopoietic cells: e.g. vascular -Non-hemopoietic cells: e.g. vascular endothelial cells, fibrocytes, epithelial cells and neuro-endocrine cells. Concept The surface molecules that appear on or The surface molecules that appear on or disappear from cell membrane during cell differentiation, development, activation.

36 CD Molecules Cell surface molecules expressed on Cell surface molecules expressed on various cell types in immune system that are named uniformly as CD(cluster of differentiation) molecules. -Surface markers that identify a particular -Surface markers that identify a particular lineage or differentiation stage. lineage or differentiation stage. -Recognized by monoclonal and named with -Recognized by monoclonal and named with CD numbers. CD numbers. -The CD molecules of human named from -The CD molecules of human named from CD1 to CD339 in 14 groups (2004). CD1 to CD339 in 14 groups (2004).

37 Groups of Human CD Molecules (2005) Groups CD Molecules （ examples ） T Lymphocyte B Lymphocyte Myeloid cells Platelet NK cells Widespread

38 Groups CD Molecules （ examples ） CAM Cytokine receptors Endothelial cells Carbohydrate Stem cells Progenitors Stem cells Continued DC Erythrocytes

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42 [Key Point] 1. Concepts: ① CAM ② LDA CD Molecules ③ CD Molecules 2. Functions of CAM