migration of leukocyte out of blood & into a particular tissue
general prcess of leukocyte movement from blood -> tissues
what do chemokines do during leukocyte “rolling”?
- activate integrins
2. trigger adhesion
once out of vessel, what helps leukocytes get to specified area?
macrophages & mast cells secrete chemokines, what do they activate?
endothelial cells, which creates an increase in adhesiveness of endothelial cells for leukocytes
what does homing require?
what is addressing?
a set of adhesion molecules on the surface of endothelial cells, they regulate lymphoid recirculation
what is the p-selectin ligand?
sialy lewis X on PSGL-1
what is the E-selectin ligand
sialy lewis CLA-1
what is the L-selectin ligand?
sialy lewis X/PNAd on Gly CAM-1 CD34
- carb-binding adhesion molecules
2. low affinity adhesion
what cytokines activate L-selectins?
IL-1 & TNF
what ligand is expression on HEV?
PNAd (Peripheral Node Addressins)
what is the integrin LFA-1 ligand?
what is the integrin Mac-1 ligand?
what is the integrin alpha4beta7 ligand?
endothelium in gut
- 2 chains that mediate adhesions
- cytoplasmic end - interacts with cytoskeleton
- extracellular end - interacts with extracellular ligands
how do integrins change affinity?
respond to intracellular signals by rapidly increasing affinity for their ligands
what are the 2 most important integrins expressed on leukocytes?
what is happening when LFA-1 & ICAM-1 bind?
a leukocyte & endothelial cell interact
when a chemokine binds to a chemokine receptor, what does this cause?
integrin activation – in leukocytes
how do you activate a T cell
Ag bind to TCR (T cell receptor)
conformational changes in extracellular domains of the integrins lead to what?
increased affinity of integrins
what is the normal conditions of integrin -leukocyte?
low affinity, bent position
what is the inflammation condition of integrin- leukocyte?
high affinity, extended position
what is it called when the extracellular domain of integrins respond to intracellular chemokine signals?
what are the 2 roles of chemokines?
- stimulate leukocyte movement
2. regulate migration of leukocytes from blood -> tissue
chemokine CXC recruits what?
chemokine CC recruits what?
chemokine CXC & CC recruit what?
what produces chemokines CXC & CC
what cytokines induce chemokine production?
TNF, IL-1, 17
activated T cells induce what chemokine?
what is the main biological action of chemokines?
enhance adhesion of circulating leukocytes to endothelium
in migration of neutrophils, what cytokines activate the endothelial cells?
TNF & IL-1
what chemokine controls transmigration of monocytes?
what selectin is needed for B/T cells to enter HEV?
what 2 chemokines are on HEV?
CCL19 & CCL21
Naive T cells do not express receptors, what is missing?
T cells can leave the LN when ______ is expressed
what mobilizes effector T cells in sits of inflammation?
what does CD44 do in terms of rolling?
mediates rolling interactions with vascular endothelial cells expressing HA (a natural ligand)
CD44 + HA = ?
inside-out (VLA-2 –VCAM binding)
what ligands are needed for naive B cells to enter via HEV?
CXCL12, CCL19, CCL21
what specifically migrates naive B cells to their zone in LNs?