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LECTURE 16 Cellular Adhesion Molecules
LECTURE 16 Cellular Adhesion Molecules
LEARNING OBJECTIVES:
LECTURE REFRENCE:
1
CELLULAR ADHESION MOLECUES
Adhesion molecules: Cell surface molecules involved in the binding of cells to extracellular matrix
or to neighboring cells, where the principal function is adhesion, rather than cell activation, e.g.,
integrins and selectins. One of the important functions of the adhesion molecules is to ensure that
cells are arrived to the required locations.
Extracellular matrix: The intercellular substance in a tissue.
- The cell adhesion molecules on the endothelium (the lining of the blood vessels) which
interact with integrins (consist of Heterodimeric molecules containing , and chains. All
members of a particular subfamily share a common chain, but each has a unique -
chain. However, there are several exceptions to this rule, and it has more recently been
found that some -chains can associate with more than one -chain). Integrins are all
members of the immunoglobulin supergene family. Integrins are a major group of adhesion
molecules, present on many cells, including leucocytes. Each member of this large family of
molecules consists of two non-covalently bound polypeptides (, and ), both of which traverse
the membrane. They fall into three major families depending on which -chain they have,
because any -chain can associate with several -chains. The ability of integrins to bind to their
ligands depends on divalent cations. For example, LFA-1 (lymphocyte functional antigen-1
12 integrin) has a mg2+ ion coordinated at the centre of a binding site which accommodates an
aspartate residue from the ligand. In addition Ca2+ ions another site causes it to dimerize at the
cell surface, thus increasing the effective affinity for its ligand intercellular adhesion molecule-
1 (ICAM-1).
The three integrin subfamilies are:
1 integrins are involved in binding of cells to extracellular matrix.
CD 29 "-chain" + various polypeptides, and includes the VLA (very late activation) markers.
- Immune cells vary in the types of molecules that cause them to roll and stop.
- Molecules that monitor and control the immune cells to roll and stop are variables form one
cell type to another, and also destination to destination is also different.
- By providing the immune cells with different adhesion molecules and by providing their
corresponding destinations with their appropriate adhesion partners ALLAH ensures that these
immune cells will be transported in to the exact position where they are needed.
Examples of some common adhesion molecules on NK-cells
- Fas ligand (FasL) is expressed on the NK cell
- Fas is a protein found on the surface of the target.
Examples of some common adhesion molecules on T, B-lymphocytes, antigen presenting
cells (APCs), and high endothelial venules in lymph node and Peyer's patches to control
lymphocyte trafficking
Virgin T and B-lymphocytes express adhesion molecules allow them to get into the secondary
lymphoid organs (e.g., Peyer's patches, and lymph nodes), but not the inflamed areas.
The experienced (previously activated) T-lymphocytes express adhesion molecules to encourage
them to re-enter the secondary lymphoid organs.
- L-Selectin on virgin T-cells binds to GlyCAM-1 on the high endothelial venules.
- Virgin T-cell express alpha 4 Beta 7 (47: the gut specific integrin), and they will express
high level 47 when they were activated in the Peyer's patches and down regulate the
expression of L-selectin. These T cells will bind to its partner Mad CAM-1 that found on the
high endothelial venules of Peyer's patches and the lymph node.
- CD2 on T-cells binds to LFA-3 on APCs.
- LFA-1 on T-cells binds to ICAM-1 on APCs.
- CD28 binds to CD80, and CD86 (B7-1, and B7-2) on APCs.
- CD 40 on B-Lymphocytes binds CD 40 L (ligand) expressed on T-lymphocytes.