Lecture 21 - T Cell Trafficking Flashcards
Definition of naive T cells
Fully-developed T cells found in lymphoid organs that have not been activated by cognate interaction
Time for a naive T cell to make a full circuit
~24 hours
Naive T cell circulation circuit 1) 2) 3) 4) 5)
1) Lymph node
2) Enters efferent lymphatics
3) Efferent lymphatics empty into thoracic duct
4) Thoracic duct returns lymph to blood
5) Enter lymph nodes through HEV
Where can naive T cells never be?
Afferent lymphatics leading to tissue, tissue
Area of an artery with the least shearing force
Marginal pool (edges of artery)
What is tissue-specific migration of T cells called?
Homing
Do selectins or integrins bind with higher affinity?
Integrins
T cell surface molecule used for rolling
L-selectin
T cell surface molecule used for adhesion to endothelial wall
LFA-1
Another name for L-selectin
CD62-L
What is CD62-L?
L-selectin
What does L-selectin bind to?
Addressins
Addressin to HEV
GlyCAM-1
Addressin to endothelial cells
CD34
Addressin to endothelial cells in gut-associated lymphoid tissues
MadCAM-1
Where is GlyCAM-1 used as an addressin?
HEV
Where is CD34 used as an addressin?
Endothelial cells
Where is MadCAM-1 used as an addressin?
Endothelial cells in gut-associated lymphoid tissue
Chemokines associated with T cell diapedesis
CCL21, CXL12
Integrins
1)
2)
3)
1) Bind tightly to ligands
2) Signal through conformational changes
3) Large family of molecules, alpha and beta subunits
What does LFA-1 bind to?
ICAM-1
ICAM-1 minding molecule
LFA-1
What stimulates a naive T cell to become more adhesive to endothelial walls?
T cell hitting arterial wall causes conformational change in adhesion molecules
What do naive T cells always express at a high level?
CCR7
Where in a lymph node do HEV lie?
Paracortex
How do naive T cells enter lymph nodes?
1)
2)
3)
1) Through HEV, into paracortex
2) Attracted to DCs with CCL19, CCL21 with CCR7
3) Probe DCs for antigen
Name of cluster of adhesion and costimulatory molecules between a T cell and a DC
Immunological synapse
What is an immunological synapse?
Collection of integrins, MHC/TCR, CD28/CD80/86 and other molecules between T cell and DC
How long do cognate T cells and DCs bind together for?
Hours
Distribution of microclusters in naive T cell
Evenly distributed
What happens to mice without LFA-1?
No T cell activation
Immunological synapse is improperly formed, even if cognate with DC
LFA-1 can’t cause tight binding of DC and T cell
State of IL-2 receptor in naive T cell
Only beta and gamma subunits present
Weakly respond to IL-2
State of IL-2 receptor in activated T cell
Alpha, beta and gamma subunits present
Strongly respond to IL-2
T cell function that requires IL-2
Entry into the cell cycle (division)
T cell retention signal in lymph node
CD69
T cell exit signal from lymph node
S1P1
How does S1P1 stimulate T-cells leaving lymph node?
S1P1 very strongly present in efferent lymph
When a T cell is activated, it begins expressing a lot of S1P1 receptor
Phenotype of T cells being retained in a lymph node
Highly express CD69 receptor, weakly express S1P1 receptor
Can a T cell strongly express both CD69 and S1P1?
No
