Adhesion Molecules Concept Naming Roles Classification

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Adhesion Molecules Concept Naming Roles Classification Slide 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 Slide 3 Slide 4 TCR complex, Co receptor, Co-stimulator receptor, immunological synapse Slide 5 Interactions between B cell and Th cell B cell activation B cell Th cell Ag processing Th cell activation Slide 6 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 Slide 7 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 Slide 8 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 Slide 9 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). Slide 10 Slide 11 Back Slide 12 Integrins Integrins consist of alpha(1-16) and beta(1 - 8) chains VLA-4 (very late antigen-4) 4 1 ------VCAM-1, LFA-1 1 2 -----ICAM-1, ICAM-2, ICAM-3 Slide 13 LFA-1 lymphocyte function associated antigen-1) thymocyte, T cell, macrophage ICAM-1 2 3 APC Slide 14 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. Slide 15 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 Slide 16 1 Involvement in lymphocyte formation and differentiation Thymocyte Epithelial cell CD2---------------IFA-3 IFA-1-------------- ICAM-1 Slide 17 2 Involvement in immune response and immune regulation Take part in recognition of immnocytes Slide 18 3 Involvement in inflammation mediate the adhesion of leukocytes with endothelial cells during inflammation. Slide 19 Transendothelial migration of leukocytes Transendothelial migration demonstrates cooperativity between leukocyte and endothelial cell adhesion molecules. Slide 20 (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.. Slide 21 Slide 22 Slide 23 4 Involvement in lymphocyte homing take part in lymphocyte homing and recirculation Homing receptor on lymphocyte: L-selectin, LFA-1, vascular addressin on HEVs: GlyCAM-1(glycosylation dependent cell adhesion molecules), CD34; ICAM-1 L-selectin ----- GlyCAM-1, CD34 LFA-1 ----- ICAM-1 Slide 24 Slide 25 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. High endothelial venule HEV Slide 26 Clinical application of CD and adhesion molecules Elucidating pathological mechanism of disease Application during diagonosis of disease Application during prevention and treatment of disease