Lecture 3 - Leukocyte Circulation Flashcards
what is migration/recruitment?
leukocyte movement from blood into tissues
what is recirculation?
lymphocytes home to secondary organs, reside transiently, return to blood
what is leukocyte homing?
migration of leukocyte out of blood into a tissue/site of infection
what is the inflammatory response?
delivers the cells and molecules of host defense to combat sites
what is the general mechanism of leukocyte recruitment?
tethering (endothelium), rolling (integrin activation), adhesion triggering, extravasation
how are endothelial cells activated at sites of infection?
by cytokines secreted from macrophages and mast cells at the sites
what are addressins?
adhesion molecules on the endothelial cell surface that regulate lymphocyte recirculation via HEV
what are the 3 types of selectins?
P(platelet), E(endothelial), L(leukocyte)
P-selectin distribution and ligand
endothelium act. by histamine and thrombin
Sialyl Lewis X on PSGL-1
E-selectin distribution and ligand
endothelium activated by TNF, IL-1
Sialyl Lewis X CLA-1 on glycoproteins, monocytes, T cells
L-selectin distribution and ligand
neuts, monos, B and T cells
Sialyl Lewis X/pNAd on GlyCAM-1, CD34, HEV, MadCAM-1
LFA-1 Distribution and Ligand
naive B and T cells
ICAM-1 and ICAM-2
Mac-1 distribution and ligand
DCs
ICAM-1 and ICAM-2
VLA-4 distribution and ligand
naive, effector, and memory T cells
VCAM-1
alpha4beta7 distribution and ligand
gut homing B and T cells, other T’s
VCAM-1 and MadCAM-1 gut endothelium
Integrin characteristics
alpha/beta heterodimers that are noncovalently linked polyp chains
how does integrin activation occur?
in all leukocytes in response to chemokine binding to chemokine receptors
when does T lymphocyte activation occur?
when Ag binds to TCRs
what kind of signaling is involved in integrin activation and what protein is used?
“inside out” by chemokines making conformational changes in the extracellular domains thus increasing affinity for the ligands
chemokine characteristics
homologous cytokines 8-10 kD with 2 internal disulfide loops
MCP-1 function
mixed leukocyte recruitment
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