Figure 28 Icam1

FIGURE 2.9 ICAM-2. Ribbon diagram. Resolution 2.2 Ä.

a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T cells and on other types of cells in association with MHC class I to activate cytotoxic T cells. On endothelial cells, it facilitates migration of activated leukocytes to the site of injury. It is the cellular receptor for a subgroup of rhinoviruses.

ICAM-1 (intercellular adhesion molecule-1) is a y interferon-induced protein which is needed for the migration of polymorphonuclear neutrophils into areas of inflammation.

Intercellular adhesion molecule-2 (ICAM-2) (Figure 2.9) is a protein that is a member of the immunoglobulin super-family that is important in cellular interactions. It is a cell surface molecule that serves as a ligand for leukocyte inte-grins. ICAM-2 facilitates lymphocytes binding to antigen-presenting cells or to endothelial cells. It binds to LFA-1, a T lymphocyte integrin.

ICAM-2: See intercellular adhesion molecule.

Intercellular adhesion molecule-3 (ICAM-3) is a leukocyte cell surface molecule that plays a critical role in the interaction of T lymphocytes with antigen presenting cells. The interaction of the T lymphocyte with an antigen presenting cell through union of ICAM-1, ICAM-2, and ICAM-3 with LFA-1 molecules is also facilitated by the interaction of the T-cell surface molecule CD2 with LFA-3 present on antigen-presenting cells.

ICAM-3: See intercellular adhesion molecule-3.

Very late activation antigens (VLA molecules) are P-1

integrins that all have the CD19 P chain in common. They were originally described on T lymphocytes grown in long-term culture but were subsequently found on additional types of leukocytes and on cells other than blood cells. VLA proteins facilitate leukocyte adherence to vascular endothelium and extracellular matrix. Resting T lymphocytes express VLA-4, VLA-5, and VLA-6. VLA-4 is expressed on multiple cells that include thymocytes, lymphocytes in blood, B and T cell lines, monocytes, NK cells, and eosinophils. The extracellular matrix ligand for VLA-4 and VLA-5 is fibronectin, and for VLA-6 it is laminin. The binding of these molecules to their ligands gives T lymphocytes costimulator signals. VLA-5 is present on monocytes, memory T lymphocytes, platelets, and fibroblasts. It facilitates B and T cell binding to fibronectin. VLA-6, which is found on platelets, T cells, thymocytes, and monocytes, mediates platelet adhesion to laminin. VLA-3, a laminin receptor, binds collagen and identifies fibronectin. It is present on B cells, the thyroid, and the renal glomerulus. Platelet VLA-2 binds to collagen only, whereas endothelial cell VLA-2 combines with collagen and laminin. Lymphocytes bind through VLA-4 to high endothelial venules and to endothelial cell surface proteins (VCAM-1) in areas of inflammation. VLA-1, which is present on activated T cells, monocytes, melanoma cells, and smooth muscle cells, binds collagen and laminin.

VLA receptors refer to a family of integrin receptors found on cell surfaces. They consist of a and P transmembrane chain heterodimers. There is a VLA-binding site at the arginine-glycine-aspartamine sequences of vitronectin and fibronectin. VLA receptors occur principally on T lymphocytes. They also bind laminin and collagen. They participate in cell-extracellular matrix interactions.

Vascular cell adhesion molecule-1 (VCAM-1) (Figure 2.10 and Figure 2.11) is a molecule that binds lymphocytes and monocytes. It is found on activated endothelial cells, dendritic cells, tissue macrophages, bone marrow fibroblasts, and myoblasts. VCAM-1 belongs to the immunoglobulin gene superfamily and is a ligand for VLA-4 (integrin a4/p1) and integrin a4/p7. It plays an important role in leukocyte recruitment to inflammatory sites and facilitates

FIGURE 2.10 VCAM-1 bound to an endothelial cell.

NH, 1

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