Lecture 16

Question 1

What happens if there is no antigen recognition in the lyphoid organs after 24hours?

Answer 1

leave the lymph node after receiving signals from S1P, and the T cells S1P-R1 binds to it

Question 2

What is S1P?

Answer 2

blood borne lipid mediator, higher concentration in blood than lymph

Question 3

Why is S1P-R1/S1P interaction not present in the blood/lymph?

Answer 3

lymphocytes are in blood/lymph: very little S1P-R1, so cell is insensitive to it

Question 4

Why is there an S1P-R1/S1P interaction in the lymphoid tissues?

Answer 4

lymphoid tissues: S1P is present in low concentrations because an enzyme breaks down S1P in tissues
- S1P-R1 reappears after a couple hours, and the cell becomes sensitive to it
- high levels of S1P-R1 on the cell surface stimulates movement of cells towards a gradient of S1P outside the lymph node

Question 5

Why do lymphocytes do repeated cycles of homing?

Answer 5

the chance that the lymphocyte will encounter the antigen that it recognizes is very low, maximizes chances by moving around

Question 6

What happens when a naive T cell DOES encounter antigen?

Answer 6

• DC and T cell are stabilized and retained in the lymph node
• the activated T cell has a delayed expression of S1P-R1, so it is not drawn out of the lymph node

Question 7

How is S1P-R1 suppressed on a T cell?

Answer 7

• makes contact with antigen, this leads to expression of CD69, which binds to S1P-R1 and keeps it inside

Question 8

when is S1P-R1/CD69 suppression complete?

Answer 8

once the T cell differentiates into an effector T cell

Question 9

How does the S1P gradient affect B cells?

Answer 9

• some B cells become plasma blasts, and migrate to the bone marrow following S1P gradient
• some B cells form germinal centres and suppress S1P-R1

Question 10

How do B cells and T cells enter the white pulp of the spleen?

Answer 10

by following the gradient of CCR7-binding chemokines

Question 11

How do naive B cells move to the follicle of the spleen?

Answer 11

following CXCL13 gradient

Question 12

How do lymphocytes egress from white pulp, red pulp, to circulation?

Answer 12

S1P and SP1R1

Question 13

How do wandering HSCs, CMPs, CLPs find their way back to the bone marrow environment? transplanted HSCs?

Answer 13

CXCL12 gradient

Question 14

Can HSCs enter an HEV?

Answer 14

no, they don’t know the secret handshake