Leukocyte Adhesion and chemotaxis Flashcards
What is leukocyte migration?
Leukocyte migration is the movement of leukocytes from the bloodstream to sites of inflammation and immune activation to participate in host defense, inflammation, repair, and resolution.
What are the five steps involved in leukocyte migration?
The five steps are tethering, rolling, activation, adhesion, and transmigration.
What are the three main adhesion molecules involved in leukocyte migration?
Selectins, integrins, and intercellular adhesion molecules (CAMs).
What role do selectins play in leukocyte tethering and rolling?
Selectins are lectin-like adhesion molecules that weakly bind to carbohydrate moieties, allowing leukocytes to tether and roll on endothelial surfaces.
What are the three types of selectins, and where are they expressed?
: L-selectin is constitutively expressed on leukocytes, P-selectin is found in platelets and endothelium, and E-selectin is expressed on endothelial cells in response to cytokines or LPS.
How does leukocyte activation affect L-selectin?
Leukocyte activation leads to a transient increase in binding, clustering of L-selectin molecules on the surface, and eventual shedding by proteolytic cleavage (Sheddase).
What are integrins, and what role do they play in leukocyte migration
Integrins are heterodimeric proteins on leukocytes that mediate firm adhesion to endothelial cells during leukocyte migration.
How are leukocyte integrins regulated?
Leukocyte integrins exist in an inactive, bent conformation. Upon activation, they undergo conformational changes and cluster, increasing their affinity for binding.
What are intercellular adhesion molecules (ICAMs), and where are they expressed?
ICAMs are part of the immunoglobulin superfamily, expressed on inflamed endothelium and antigen-presenting cells (APCs). They serve as ligands for integrins.
What is the difference between ICAM-1 and ICAM-2?
ICAM-2 is basally expressed on endothelium, while ICAM-1 is induced by pro-inflammatory cytokines like IL-1 and TNF.
What is transmigration (diapedesis)?
Transmigration is the process by which leukocytes pass through endothelial cells to enter tissues, typically occurring between endothelial cell junctions (paracellular) or through endothelial cells (transcellular).
What are matrix metalloproteinases (MMPs), and what role do they play in transmigration?
MMPs are zinc-binding enzymes that degrade the extracellular matrix, promoting leukocyte migration through tight junctions and modulating the expression of adhesion molecules and chemokines.
What is chemotaxis?
Chemotaxis is the process by which cells move directionally in response to a chemical gradient, typically guided by chemoattractants.
What are chemotaxins?
Chemotaxins are molecules that induce chemotaxis, attracting immune cells to sites of inflammation. Non-selective examples include C3a, C5a, and LTB4, while chemokines are selective chemotactic cytokines
What are chemokines, and how are they structured?
Chemokines are a type of chemotactic cytokine that guide leukocytes. They are structurally defined and signal through G-protein coupled receptors. They belong to four families: CXC, CC, CX3C, and XC.
What is the role of chemokine receptors, and how do they function?
Chemokine receptors bind to chemokines and have a 7-transmembrane structure coupled to G-proteins for signal transduction. There are about 20 types that guide immune cell migration.
What is selectivity in the inflammatory response?
Selectivity refers to the fact that different cell types migrate at different rates to inflammation sites. For example, neutrophils are associated with acute inflammation, while monocytes and lymphocytes are linked to chronic inflammation.
How do adhesion molecules and chemokine receptors play a role in disease?
Defects in adhesion molecules can lead to leukocyte adhesion deficiencies, and viruses like HIV use chemokine receptors (CXCR4 and CCR5) to enter T-cells
What are the main roles of selectins and integrins in leukocyte adhesion?
Selectins are involved in tethering and rolling leukocytes on the endothelium, while integrins and CAMs are essential for firm adhesion and subsequent transmigration into tissues.
What is the role of MMPs in leukocyte extravasation?
MMPs (Matrix Metalloproteinases) degrade the basement membrane, facilitating leukocyte movement through endothelial cell junctions during diapedesis.
