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Adhesion Molecules

Adhesion Molecules. Concept Naming Roles Classification. Concept. Cell adhesion molecules (CAMs): proteins which exist in cell surface involve in the binding of cells to each other or to extracellular matrix. Exist as couples( receptor-ligand) Co-effect with many couples.

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Adhesion Molecules

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  1. Adhesion Molecules • Concept • Naming • Roles • Classification

  2. Concept • Cell adhesion molecules (CAMs): proteins which exist in cell surface involve in the binding of cells to each other or to extracellular matrix. • Exist as couples( receptor-ligand) • Co-effect with many couples

  3. TCR complex, Co –receptor, Co-stimulator receptor, immunological synapse

  4. Th cell B cell Th cell activation Ag processing B cell activation Interactions between B cell and Th cell

  5. Naming • Functions： ICAM-1 (intercellular adhesion molecules), LFA-1 (lymphocyte function – associated antigen-1) VCAM (vascular cell adhesion molecules), PECAM1(platelet-endothelial-cell adhesion molecule), • CD CD58, CD152

  6. Leukocyte differentiation antigen: Cell surface molecules expressed (or disappeared) on different developmental and differential phases of blood cells . CD: cluster of differentiation (uses of McAb) CD molecules: The same differentiation antigen recognized by different monoclone antibodies from different labs is called CD molecule. Naming by method of identification CD molecules have a variety of functions

  7. Classification Most of the CAMs can be grouped by structure into five families: • Immunoglobulin (Ig) superfamily • Integrin family • Selectin family • Cadherin family • Mucin-like family Others

  8. Ig superfamily CAMs • The structure of these adhesion molecules resemble that of Ig. • Members of the Ig superfamily include the intercellular adhesion molecules (ICAMs), vascular cell adhesion molecule (VCAM-1), platelet-endothelial-cell adhesion molecule (PECAM-1), and neural cell adhesion molecule (NCAM).

  9. Back

  10. Integrins Integrins consist of alpha(1-16) and beta(1 - 8) chains VLA-4 (very late antigen-4)（α4β1）------VCAM-1, LFA-1 （α1β2）-----ICAM-1, ICAM-2, ICAM-3

  11. 举例：LFA-1（lymphocyte function associated antigen-1) • 分布：thymocyte, T cell, macrophage • 配体：ICAM-1、2、3（表达于APC、内皮细胞）

  12. Selectins The molecule consists of one peptide chain which has carbohydrate-binding domain. • Bing to Sialyl-Lewis (sialyl Louis)oligosaccharides • three family members: endothelial (E)-selectin, leukocyte (L)-selectin, and platelet (P)-selectin.

  13. Roles— functions of cell adhesion molecules To mediate the contact and adhesion between cell and cell, or between cell and extracellular matrix resulting to various biologic effects. Cell surface adhesion molecules play vital roles in numerous cellular processes. 1 Involvement in lymphocyte formation and differentiation 2 Involvement in immune response and immune regulation 3 Involvement in inflammation 4 Involvement in lymphocyte homing 5 Involvement in regulation of apoptosis

  14. 1 Involvement in lymphocyte formation and differentiation Thymocyte Epithelial cell CD2---------------IFA-3 IFA-1-------------- ICAM-1

  15. 2 Involvement in immune response and immune regulationTake part in recognition of immnocytes

  16. 3 Involvement in inflammation · mediate the adhesion of leukocytes with endothelial cells during inflammation.

  17. Transendothelial migration of leukocytes Transendothelial migration demonstrates cooperativity between leukocyte and endothelial cell adhesion molecules.

  18. (1) rolling, Initial rolling is mediated by binding of E-selectin molecules on the vascular endothelium to sialylated carbohydrate moieties on mucinlike CAMs. (2) activation by chemoattractant stimulus, A chemokine such as IL-8 then binds to its receptor on the neutrophil, triggering an activating signal. This signal induces a conformational change in the integrin molecules, enabling them to adhere firmly to Ig-superfamily molecules on the endothelium (3) arrest and adhesion, The interaction between integrins and Ig-superfamily CAMs stabilizes adhesion of the neutrophil to the endothelial cell, enabling the cell to adhere firmly to the endothelial cell. (4) transendothelial migration Transmigration of the leukocyte through adjacent endothelial cells in a process called diapedesis.PECAM-1 is a crucial player in this step. This step is largely unknown. .

  19. 4 Involvement in lymphocyte homing · take part in lymphocyte homing and recirculationHoming receptor on lymphocyte: L-selectin, LFA-1,vascular addressin on HEVs: GlyCAM-1(glycosylation dependent cell adhesion molecules), CD34; ICAM-1L-selectin ----- GlyCAM-1, CD34LFA-1 ----- ICAM-1

  20. 淋巴细胞定向迁移，分布于淋巴器官和组织的不同部位淋巴细胞定向迁移，分布于淋巴器官和组织的不同部位

  21. High endothelial venule，HEV（高内皮毛细血管后微静脉） HEV are specialized venules found in lymphoid tissues. Lymphocytes migrate from blood into lymphoid tissues by attaching to and migrating across the high endothelial cells of the vessels.

  22. Clinical application of CD and adhesion molecules • Elucidating pathological mechanism of disease • Application during diagonosis of disease • Application during prevention and treatment of disease

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