In molecular biology, intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) are part of the immunoglobulin superfamily. They are important in inflammation, immune responses and in intracellular signalling events. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11/CD18 such as LFA-1 and Macrophage-1 antigen, during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma, due to activation and proteolysis mechanisms at cell surfaces.
Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
CD11c, also known as Integrin, alpha X (ITGAX), is a gene that encodes for CD11c.
Integrin, alpha L , also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene. CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.
Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3). ITGAM is also known as CR3A, and cluster of differentiation molecule 11B (CD11B). The second chain of αMβ2 is the common integrin β2 subunit known as CD18, and integrin αMβ2 thus belongs to the β2 subfamily integrins.
In cell biology, CD11 is the α (alpha) component of various integrins, especially ones in which the β (beta) component is CD18 (β2) and mediate leukocyte adhesion. For example,
Lymphocyte function-associated antigen 1 (LFA-1) is an integrin found on lymphocytes and other leukocytes. LFA-1 plays a key role in emigration, which is the process by which leukocytes leave the bloodstream to enter the tissues. LFA-1 also mediates firm arrest of leukocytes. Additionally, LFA-1 is involved in the process of cytotoxic T cell mediated killing as well as antibody mediated killing by granulocytes and monocytes. As of 2007, LFA-1 has 6 known ligands: ICAM-1, ICAM-2, ICAM-3, ICAM-4, ICAM-5, and JAM-A. LFA-1/ICAM-1 interactions have recently been shown to stimulate signaling pathways that influence T cell differentiation. LFA-1 belongs to the integrin superfamily of adhesion molecules.
Macrophage-1 antigen is a complement receptor ("CR3") consisting of CD11b and CD18.
Leukocyte extravasation is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.
Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.
Intercellular adhesion molecule 2 (ICAM2), also known as CD102, is a human gene, and the protein resulting from it.
Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.
Integrin alpha-D is a protein that in humans is encoded by the ITGAD gene.
The following outline is provided as an overview of and topical guide to immunology:
Rap1 is a small GTPase, which are small cytosolic proteins that act like cellular switches and are vital for effective signal transduction. There are two isoforms of the Rap1 protein, each encoded by a separate gene, RAP1A and RAP1B. Rap1 belongs to Ras-related protein family.
The von Willebrand factor type A (vWA) domain is a protein domain named after its occurrence in von Willebrand factor (vWF), a large multimeric glycoprotein found in blood plasma. Mutant forms of vWF are involved in the aetiology of bleeding disorders. This type A domain is the prototype for a protein superfamily.
A catch bond is a type of noncovalent bond whose dissociation lifetime increases with tensile force applied to the bond. Normally, bond lifetimes are expected to diminish with force. In the case of catch bonds, the lifetime of the bond actually increases up to a maximum before it decreases like in a normal bond. Catch bonds work in a way that is conceptually similar to that of a Chinese finger trap. While catch bonds are strengthened by an increase in force, the force increase is not necessary for the bond to work. Catch bonds were suspected for many years to play a role in the rolling of leukocytes, being strong enough to roll in presence of high forces caused by high shear stresses, while avoiding getting stuck in capillaries where the fluid flow, and therefore shear stress, is low. The existence of catch bonds was debated for many years until strong evidence of their existence was found in bacteria. Definite proof of their existence came shortly thereafter in leukocytes.
Fermitin family homolog 3) (FERMT3), also known as kindlin-3 (KIND3), MIG2-like protein (MIG2B), or unc-112-related protein 2 (URP2) is a protein that in humans is encoded by the FERMT3 gene. The kindlin family of proteins, member of the B4.1 superfamily, comprises three conserved protein homologues, kindlin 1, 2, and 3. They each contain a bipartite FERM domain comprising four subdomains F0, F1, F2, and F3 that show homology with the FERM head (H) domain of the cytoskeletal Talin protein. Kindlins have been linked to Kindler syndrome, leukocyte adhesion deficiency, cancer and other acquired human diseases. They are essential in the organisation of focal adhesions that mediate cell-extracellular matrix junctions and are involved in other cellular compartments that control cell-cell contacts and nucleus functioning. Therefore, they are responsible for cell to cell crosstalk via cell-cell contacts and integrin mediated cell adhesion through focal adhesion proteins and as specialised adhesion structures of hematopoietic cells they are also present in podosome's F actin surrounding ring structure. Isoform 2 may act as a repressor of NF-kappa-B and apoptosis
Nancy Hogg FMedSci is an immunologist who has made major contributions in the field of adhesion molecules, focusing on the integrins expressed by leukocytes. Hogg was elected to the Academy of Medical Sciences in 2002 and currently holds an emeritus position at the Francis Crick Institute, London.
