Lecture 3 - Leukocyte Circulation

Question 0

what is migration/recruitment?

Answer 0

leukocyte movement from blood into tissues

Question 1

what is recirculation?

Answer 1

lymphocytes home to secondary organs, reside transiently, return to blood

Question 2

what is leukocyte homing?

Answer 2

migration of leukocyte out of blood into a tissue/site of infection

Question 3

what is the inflammatory response?

Answer 3

delivers the cells and molecules of host defense to combat sites

Question 4

what is the general mechanism of leukocyte recruitment?

Answer 4

tethering (endothelium), rolling (integrin activation), adhesion triggering, extravasation

Question 5

how are endothelial cells activated at sites of infection?

Answer 5

by cytokines secreted from macrophages and mast cells at the sites

Question 6

what are addressins?

Answer 6

adhesion molecules on the endothelial cell surface that regulate lymphocyte recirculation via HEV

Question 7

what are the 3 types of selectins?

Answer 7

P(platelet), E(endothelial), L(leukocyte)

Question 8

P-selectin distribution and ligand

Answer 8

endothelium act. by histamine and thrombin

Sialyl Lewis X on PSGL-1

Question 9

E-selectin distribution and ligand

Answer 9

endothelium activated by TNF, IL-1

Sialyl Lewis X CLA-1 on glycoproteins, monocytes, T cells

Question 10

L-selectin distribution and ligand

Answer 10

neuts, monos, B and T cells

Sialyl Lewis X/pNAd on GlyCAM-1, CD34, HEV, MadCAM-1

Question 11

LFA-1 Distribution and Ligand

Answer 11

naive B and T cells

ICAM-1 and ICAM-2

Question 12

Mac-1 distribution and ligand

Answer 12

DCs

ICAM-1 and ICAM-2

Question 13

VLA-4 distribution and ligand

Answer 13

naive, effector, and memory T cells

VCAM-1

Question 14

alpha4beta7 distribution and ligand

Answer 14

gut homing B and T cells, other T’s

VCAM-1 and MadCAM-1 gut endothelium

Question 15

Integrin characteristics

Answer 15

alpha/beta heterodimers that are noncovalently linked polyp chains

Question 16

how does integrin activation occur?

Answer 16

in all leukocytes in response to chemokine binding to chemokine receptors

Question 17

when does T lymphocyte activation occur?

Answer 17

when Ag binds to TCRs

Question 18

what kind of signaling is involved in integrin activation and what protein is used?

Answer 18

“inside out” by chemokines making conformational changes in the extracellular domains thus increasing affinity for the ligands

Question 19

chemokine characteristics

Answer 19

homologous cytokines 8-10 kD with 2 internal disulfide loops

Question 20

MCP-1 function

Answer 20

mixed leukocyte recruitment

cc

Question 21

MIP-3beta function

Answer 21

T cell and DC migration into parafollicular zones of LNs

cc

Question 22

SLC function

Answer 22

T cell and DC migration into LNs

cc

Question 23

ENA-78 function

Answer 23

neutrophil recruitment

cxc

Question 24

IL-8 function

Answer 24

neutrophil recruitment cxc

Question 25

IP-10 function

Answer 25

Effector T cell recruitment cxc

Question 26

SDF-alphabeta

Answer 26

mixed leukocyte recruitment, HIV coreceptor cxc

Question 27

BCA-1 function

Answer 27

B cell migration into follicles; T follicular helper cell migration into follicles cxc

Question 28

Lymphotactin function

Answer 28

T and NK cell recruitment c

Question 29

Fractalkine function

Answer 29

T, NK, monocyte recruitment, CTL and NK activation cx3c

Question 30

how are neutrophils and monocytes recruited into infected tissues?

Answer 30

without activation and enter through post-capillary venules except parenchymal tissues (liver, lungs, kidney)

Question 31

what initiates rolling and then stabilizes it?

Answer 31

P-selectin and ligand interaction L-selectin binding to ligand IL-8 stabilizes it

Question 32

what controls transmigration of monocytes?

Answer 32

MCP-1

Question 33

What happens after diapedesis?

Answer 33

cells adopt an ameboid shape and migrate in a polarized fashion along collagen fibrils to infection site

Question 34

where are chemotactic receptors located?

Answer 34

the leading edge

Question 35

what is expressed by both T and B lymphocytes

Answer 35

L-selectin

Question 36

how do naive lymphocytes enter the LN?

Answer 36

through HEVs ligand on HEV called pNAd

Question 37

where are HEVs present

Answer 37

only on secondary lymphoid organs

Question 38

what chemokines are displayed on the HEV surface?

Answer 38

MIP-3beta and SLC

Question 39

What chemokine binding receptor activates integrins?

Answer 39

CCR7

Question 40

what do naive T cells have low levels of and why?

Answer 40

S1PR1 bc receptor is internalized after S1P binding in blood

Question 41

when can naive T cells exit LN?

Answer 41

for several hours until S1PR1 is re-expressed

Question 42

what do Ag-activated T cells have and when do they leave LN?

Answer 42

low levels of S1PR1, leave after several days when effector T cells sens the S1P gradient

Question 43

Where do activated effector T cells home to?

Answer 43

sites of infection in peripheral tissues

Question 44

what is cell migration into tissue mediated by?

Answer 44

E-selectin, P-selectin, integrins and IP-10

Question 45

what does CD44 do

Answer 45

mediates rolling interactions with cells expressing HA, its ligand, or E-selectin

Question 46

what is CD44 important for? what is secreted by what?

Answer 46

mobilization of effector T cells in sites of infection endothelial cells will secrete chemokines and express E,P-selectins and hyaluronic acid(HA)

Question 47

What does VLA-4 do

Answer 47

enhances adhesiveness ("inside out" signaling) after chemokine signaling via GPCRs

Question 48

maturation of Follicular B cell pathway

Answer 48

immature B cell --> red pulp --> white pulp periphery, express CXCR5 in response to BCA-1 (helps movement to white pulp)

Question 49

where is maturation completed for B cells and what do they do

Answer 49

in white pulp, reenter circulation and home to LNs as mature naive B cells

Question 50

What does the B cell homing process require?

Answer 50

chemokines SDF-1alphabeta, MIP-3beta, and SLC on HEV

Question 51

where are B cells migrating into follicles and what drives the process?

Answer 51

stroma, BCA-1 with receptor CXCR5 in follicles B cells may encounter Ag and become activated

Question 52

What are 4 major integrin molecules?

Answer 52

LFA-1, Mac-1, VLA-4, alpha4-beta7