Lecture 3: Leukocyte Circulation and Migration into Tissue Flashcards
What is recirculation the ability of lymphocytes to repeatedly do?
1) home to secondary lymphoid organs
2) reside there transiently
3) return to the blood
What is leukocyte homing?
Cell migration out of the blood and into peripheral tissues, or to a site of an infection or injury.
What is a major part of inflammation?
Recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury.
Does inflammation cause tissue damage?
Yes
What are the 4 steps in the cascade of adhesive and activation events in leukocyte recruitment?
1) tethering
2) rolling
3) adhesion and stop
4) transmigration in to the tissue
What is tethering?
occurs through transient interactions of selectins and integrins with their ligands
What is rolling?
allows chemokine receptors on leukocytes to bind chemokines expressed on endothelium
What is adhesion and stop?
Receptors signal and activate integrins on leukocytes which interact with ligands expressed on endothelium and trigger adhesion to the endothelium.
What is transmigration in to the tissue?
Leukocyte then transmigrate into the extravascular space where they can migrate down chemokine gradients towards specific areas.
Do endothelial cells in healthy tissues express adhesion molecules on their surfaces facing the blood?
No
What activates the endothelial cells at sites of infection and tissue injury to express adhesion molecules?
cytokines secreted by resident immune cells at these sites
Fill in the Blank:
Homin involves molecules on the surfaces of both the leukocyte (_________________) and endothelial cells (______).
homing receptors and chemokine receptors; chemokines
What are addressins?
comprise a set of several adhesion molecules on the surface of endothelial cells
What are the 3 types of selectins?
P-selectin (CD62P)
E-selectin (CD62E)
L-selectin (CD62L)
What type of selectin is expressed on endothelium activated by histamine or thrombin?
P-selectin (CD62P)
What is the ligand molecule for P-selectin?
Sialyl Lewis X on PSGL-1 and other glycoproteins
What causes the expression of E-selectin (CD62E) on endothelium?
activated by cytokines TNF and IL-1
What causes the expression of L-selectin (CD62L) on endothelium?
neutrophils, monocytes, T cells (naive and central memory), B cells (naive)
What cell types express the ligand that binds to P-selectin?
neutrophils
monocytes
T cells (effector, memory)
What is the ligand molecule for E-selectin?
Sialyl Lewis X (e.g., CLA-1) on glycoproteins
What cell types express the ligand that binds to E-selectin?
neutrophils
monocytes
T cells (effector, memory)
What ligand molecule binds to L-selectin?
Sialyl Lewis X/PNAd on GlyCAM-1, CD34, MadCAM-1, others
What cell types express the ligand that binds to L-selectin?
endothelium (HEV)
Which cell type expresses P-selectin and E-selectin?
endothelial cells
True or False:
E-selectin is synthesized and expressed on the endothlial cell surface within 1 to 2 hours in response to the cytokines IL-1 and TNF produced by tissue macrophages in response to infection.
True
Is L-selectin expressed on endothelial cells?
No - expressed on leukocytes and lymphocytes
What is another name for L-selectin ligands expressed on HEV?
peripheral node addressins (PNAd)
What cells express LFA-1 integrins?
neutrophils
monocytes
T cells (naive, effector, memory)
B cells (naive)
What cells express Mac-1 integrins?
neutrophils
monocytes
dendritic cells
What cells express VLA-4 integrins?
monocytes T cells (naive, effector, memory)
What cells express alpha 4 beta 7 integrins?
monocytes T cells (gut homing, naive, effector, memory) B cells (gut homing)
What ligand molecules bind to LFA-1 and Mac-1 integrins?
ICAM-1 (CD54)
ICAM-2 (CD102)
What type of cell expresses ligands ICAM1 and ICAM2?
endothelium (cytokine induced)
What ligand molecule binds to VLA-4 and alpha4beta7?
VCAM-1 (CD106)
MadCAM-1 also binds to alpha4beta7
Which cell type expresses VCAM-1 (CD106)
endothelium (cytokine-induced)
endothelium in gut and gut-associated lymphoid tissues
In what type of endothelium is MadCAM-1 expressed?
endothelium in gut and gut-associated lymphoid tissues
