Lecture 3 - Leukocyte Circulation Flashcards

0
Q

what is migration/recruitment?

A

leukocyte movement from blood into tissues

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1
Q

what is recirculation?

A

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

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2
Q

what is leukocyte homing?

A

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

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3
Q

what is the inflammatory response?

A

delivers the cells and molecules of host defense to combat sites

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4
Q

what is the general mechanism of leukocyte recruitment?

A

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

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5
Q

how are endothelial cells activated at sites of infection?

A

by cytokines secreted from macrophages and mast cells at the sites

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6
Q

what are addressins?

A

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

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7
Q

what are the 3 types of selectins?

A

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

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8
Q

P-selectin distribution and ligand

A

endothelium act. by histamine and thrombin

Sialyl Lewis X on PSGL-1

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9
Q

E-selectin distribution and ligand

A

endothelium activated by TNF, IL-1

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

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10
Q

L-selectin distribution and ligand

A

neuts, monos, B and T cells

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

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11
Q

LFA-1 Distribution and Ligand

A

naive B and T cells

ICAM-1 and ICAM-2

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12
Q

Mac-1 distribution and ligand

A

DCs

ICAM-1 and ICAM-2

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13
Q

VLA-4 distribution and ligand

A

naive, effector, and memory T cells

VCAM-1

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14
Q

alpha4beta7 distribution and ligand

A

gut homing B and T cells, other T’s

VCAM-1 and MadCAM-1 gut endothelium

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15
Q

Integrin characteristics

A

alpha/beta heterodimers that are noncovalently linked polyp chains

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16
Q

how does integrin activation occur?

A

in all leukocytes in response to chemokine binding to chemokine receptors

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17
Q

when does T lymphocyte activation occur?

A

when Ag binds to TCRs

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18
Q

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

A

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

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19
Q

chemokine characteristics

A

homologous cytokines 8-10 kD with 2 internal disulfide loops

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20
Q

MCP-1 function

A

mixed leukocyte recruitment

cc

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21
Q

MIP-3beta function

A

T cell and DC migration into parafollicular zones of LNs

cc

22
Q

SLC function

A

T cell and DC migration into LNs

cc

23
Q

ENA-78 function

A

neutrophil recruitment

cxc

24
Q

IL-8 function

A

neutrophil recruitment

cxc

25
Q

IP-10 function

A

Effector T cell recruitment

cxc

26
Q

SDF-alphabeta

A

mixed leukocyte recruitment, HIV coreceptor

cxc

27
Q

BCA-1 function

A

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

cxc

28
Q

Lymphotactin function

A

T and NK cell recruitment

c

29
Q

Fractalkine function

A

T, NK, monocyte recruitment, CTL and NK activation

cx3c

30
Q

how are neutrophils and monocytes recruited into infected tissues?

A

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

31
Q

what initiates rolling and then stabilizes it?

A

P-selectin and ligand interaction

L-selectin binding to ligand IL-8 stabilizes it

32
Q

what controls transmigration of monocytes?

A

MCP-1

33
Q

What happens after diapedesis?

A

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

34
Q

where are chemotactic receptors located?

A

the leading edge

35
Q

what is expressed by both T and B lymphocytes

A

L-selectin

36
Q

how do naive lymphocytes enter the LN?

A

through HEVs

ligand on HEV called pNAd

37
Q

where are HEVs present

A

only on secondary lymphoid organs

38
Q

what chemokines are displayed on the HEV surface?

A

MIP-3beta and SLC

39
Q

What chemokine binding receptor activates integrins?

A

CCR7

40
Q

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

A

S1PR1 bc receptor is internalized after S1P binding in blood

41
Q

when can naive T cells exit LN?

A

for several hours until S1PR1 is re-expressed

42
Q

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

A

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

43
Q

Where do activated effector T cells home to?

A

sites of infection in peripheral tissues

44
Q

what is cell migration into tissue mediated by?

A

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

45
Q

what does CD44 do

A

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

46
Q

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

A

mobilization of effector T cells in sites of infection

endothelial cells will secrete chemokines and express E,P-selectins and hyaluronic acid(HA)

47
Q

What does VLA-4 do

A

enhances adhesiveness (“inside out” signaling)

after chemokine signaling via GPCRs

48
Q

maturation of Follicular B cell pathway

A

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

49
Q

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

A

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

50
Q

What does the B cell homing process require?

A

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

51
Q

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

A

stroma, BCA-1 with receptor CXCR5

in follicles B cells may encounter Ag and become activated

52
Q

What are 4 major integrin molecules?

A

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