lecture 3 Flashcards
leukocyte homing
migration of leukocyte out of blood & into a particular tissue
mirgration/recruitment
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?
chemokine gradients
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?
temporary adhesion
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
selectin characteristics
- 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?
I-CAM-1
I-CAM-2
endothelium
what is the integrin Mac-1 ligand?
I-CAM-1
I-CAM-2
endothelium
what is the integrin alpha4beta7 ligand?
V-CAM-1
Mad CAM-1
endothelium in gut
integrin characteristics
- 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?
- LFA-1
2. VLA-4
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?
inside-out signaling
what are the 2 roles of chemokines?
- stimulate leukocyte movement
2. regulate migration of leukocytes from blood -> tissue
chemokine CXC recruits what?
neutrophils
chemokine CC recruits what?
monocytes
chemokine CXC & CC recruit what?
lymphocytes
what produces chemokines CXC & CC
leukocytes
what cytokines induce chemokine production?
TNF, IL-1, 17
activated T cells induce what chemokine?
CC
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?
CCL2
what selectin is needed for B/T cells to enter HEV?
L-selectin (PNAd)
what 2 chemokines are on HEV?
CCL19 & CCL21
Naive T cells do not express receptors, what is missing?
S1PR1
T cells can leave the LN when ______ is expressed
S1PR1
what mobilizes effector T cells in sits of inflammation?
CD44
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?
CXCL13
