lecture 3

Question 0

leukocyte homing

Answer 0

migration of leukocyte out of blood & into a particular tissue

Question 1

mirgration/recruitment

Answer 1

general prcess of leukocyte movement from blood -> tissues

Question 2

what do chemokines do during leukocyte “rolling”?

Answer 2

1. activate integrins

2. trigger adhesion

Question 3

once out of vessel, what helps leukocytes get to specified area?

Answer 3

chemokine gradients

Question 4

macrophages & mast cells secrete chemokines, what do they activate?

Answer 4

endothelial cells, which creates an increase in adhesiveness of endothelial cells for leukocytes

Question 5

what does homing require?

Answer 5

temporary adhesion

Question 6

what is addressing?

Answer 6

a set of adhesion molecules on the surface of endothelial cells, they regulate lymphoid recirculation

Question 7

what is the p-selectin ligand?

Answer 7

sialy lewis X on PSGL-1

Question 8

what is the E-selectin ligand

Answer 8

sialy lewis CLA-1

Question 9

what is the L-selectin ligand?

Answer 9

sialy lewis X/PNAd on Gly CAM-1 CD34

Question 10

selectin characteristics

Answer 10

1. carb-binding adhesion molecules

2. low affinity adhesion

Question 11

what cytokines activate L-selectins?

Answer 11

IL-1 & TNF

Question 12

what ligand is expression on HEV?

Answer 12

PNAd (Peripheral Node Addressins)

Question 13

what is the integrin LFA-1 ligand?

Answer 13

I-CAM-1
I-CAM-2
endothelium

Question 14

what is the integrin Mac-1 ligand?

Answer 14

I-CAM-1
I-CAM-2
endothelium

Question 15

what is the integrin alpha4beta7 ligand?

Answer 15

V-CAM-1
Mad CAM-1
endothelium in gut

Question 16

integrin characteristics

Answer 16

1. 2 chains that mediate adhesions
2. cytoplasmic end - interacts with cytoskeleton
3. extracellular end - interacts with extracellular ligands

Question 17

how do integrins change affinity?

Answer 17

respond to intracellular signals by rapidly increasing affinity for their ligands

Question 18

what are the 2 most important integrins expressed on leukocytes?

Answer 18

1. LFA-1

2. VLA-4

Question 19

what is happening when LFA-1 & ICAM-1 bind?

Answer 19

a leukocyte & endothelial cell interact

Question 20

when a chemokine binds to a chemokine receptor, what does this cause?

Answer 20

integrin activation – in leukocytes

Question 21

how do you activate a T cell

Answer 21

Ag bind to TCR (T cell receptor)

Question 22

conformational changes in extracellular domains of the integrins lead to what?

Answer 22

increased affinity of integrins

Question 23

what is the normal conditions of integrin -leukocyte?

Answer 23

low affinity, bent position

Question 24

what is the inflammation condition of integrin- leukocyte?

Answer 24

high affinity, extended position

Question 25

what is it called when the extracellular domain of integrins respond to intracellular chemokine signals?

Answer 25

inside-out signaling

Question 26

what are the 2 roles of chemokines?

Answer 26

1. stimulate leukocyte movement

2. regulate migration of leukocytes from blood -> tissue

Question 27

chemokine CXC recruits what?

Answer 27

neutrophils

Question 28

chemokine CC recruits what?

Answer 28

monocytes

Question 29

chemokine CXC & CC recruit what?

Answer 29

lymphocytes

Question 30

what produces chemokines CXC & CC

Answer 30

leukocytes

Question 31

what cytokines induce chemokine production?

Answer 31

TNF, IL-1, 17

Question 32

activated T cells induce what chemokine?

Answer 32

CC

Question 33

what is the main biological action of chemokines?

Answer 33

enhance adhesion of circulating leukocytes to endothelium

Question 34

in migration of neutrophils, what cytokines activate the endothelial cells?

Answer 34

TNF & IL-1

Question 35

what chemokine controls transmigration of monocytes?

Answer 35

CCL2

Question 36

what selectin is needed for B/T cells to enter HEV?

Answer 36

L-selectin (PNAd)

Question 37

what 2 chemokines are on HEV?

Answer 37

CCL19 & CCL21

Question 38

Naive T cells do not express receptors, what is missing?

Answer 38

S1PR1

Question 39

T cells can leave the LN when ______ is expressed

Answer 39

S1PR1

Question 40

what mobilizes effector T cells in sits of inflammation?

Answer 40

CD44

Question 41

what does CD44 do in terms of rolling?

Answer 41

mediates rolling interactions with vascular endothelial cells expressing HA (a natural ligand)

Question 42

CD44 + HA = ?

Answer 42

inside-out (VLA-2 –VCAM binding)

Question 43

what ligands are needed for naive B cells to enter via HEV?

Answer 43

CXCL12, CCL19, CCL21

Question 44

what specifically migrates naive B cells to their zone in LNs?

Answer 44

CXCL13