Leukocyte migration DSA (bowden) Flashcards
Leukocyte homing
migration on a particular type of leukocyte into a restricted type of tissue or a tissue with ongoing infection or injury
recruitment
general process of leukocyte movement from blood into tissues
inflammation
the recruitment of leukocytes and plasma proteins form the blood to sites of infection and tissue injury
triggered by recognition of microbes and dead tissues (innate) and prolonged and refined in adaptive immunity
Selectins
Plasma membrane carbohydrate-binding adhesion molecules that mediate an initial step of low-affinity adhesion of circulating leukocytes to endothelial cells lining postcapillary venues
location of selectin ligand
on leukocyte
location of selectin
endothelial cell
P-selectin
(CD62P)
stored in cytoplasmic granules of endothelial cells
rapidly redistributed to the surface in response to: microbial products cytokines histamine from mast cells thrombin (during coagulation)
E-Selectin
(CD62E)
synthesized and expressed on the endothelial cell surface within 1-2 hours in response to the cytokines IL-1, TNF, LPS
L-Selectin
A selectin expressed on leukocytes but not on endothelial cells
L-selectin on neutrophils serves to bind these cells to endothelial cells that are activated by IL-1, TNF and other cytokines
Integrins
heterodimeric cell surface proteins
composed on two noncovalently linked polypeptide chains
mediate adhesions of cells to other cells or to ECM through specific binding interactions with various ligands
LFA-1
integrin expressed on leukocytes
early neutrophils
ligand is ICAM-1
VLA-4
integrin expressed on leukocytes
monocytes
ligand is VCAM-1 which is expressed on cytokine activated endothelial cells in some tissues
this interaction is important for leukocyte recruitment into inflammatory sites
ICAM-1
ligand for LFA-1 (integrin)
this is a membrane glycoprotein expressed on cytokine-activated endothelial cells and lymphocytes, dendritic cells, magrophages, fibroblasts, and keratinocytes
important in leukocyte-endothelial interactions
Activation
important feature of integrins. Their ability to respond to intracellular signals by rapidly increasing their affinity for their ligands
Chemokine receptor signalling
if a leukocyte comes close to endothelial cells such as when selectin-dependent rolling of leukoctyes occurs, then chemokines on endothelial surface can bind chemokine receptors on leukocytes
this activates leukocyte integrins increasing their affinity for their ligands on the endothelial cells
chemokines also induce integrin clustering leading to tighter binding of the leukocytes to the endothelium
location of chemokine receptor
leukocytes
location of chemokine
endothelial surface
chemokines
structurally homologous cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues
what type of receptor is a chemokine
G protein coupled receptor
CCL2
Chemokine
Major function - Mixed leukocyte recruitment
receptor - CCR2
Original name (MCP-1)
CCL7
(MCP -3)
Chemokine receptor - CCR2, CCR2, CCR3
major function - mixed leukocyte recruitment
CCL5
(rantes)
chemokine receptor - CCR1, CCR3, CCR5
mixed leukocyte recruitment
CXCL8
original name (IL-8)
Chemokine receptor (CXCR1, CXCR2)
Neutrophil recruitment
what do chemokines bind to
bind to heparan sulfate proteoglycans on endothelial tissues that line postcapillary venues and are displayed in this way to circulating leukocytes
chemokines then bind to receptors on leukocytes
Chemokinesis
extravascular chemokines stimulate movement of leukocytes and their migration toward the chemical gradient of the secrete protein – leukocytes move toward infected cells
Steps in migration of leukocytes into tissues
1) Selectin-mediated rolling of leukocytes on endothelium
2) Chemokine-mediated increase in affinity of integrins
3) Stable integrin-mediated adhesion of leukocytes to endothelium due to cytokines (TNF, IL-1) enhancing endothelial expression of integrin ligands
4) Transmigration of leukocytes through the endothelium
Paracellular transmigration
leukocytes transmigrate b/w the borders of endothelial cells
Transcellular migration
leukocytes move through endothelial cells rather than between them, less understood mechanism
