Leukocyte migration DSA (bowden)

Question 1

Leukocyte homing

Answer 1

migration on a particular type of leukocyte into a restricted type of tissue or a tissue with ongoing infection or injury

Question 2

recruitment

Answer 2

general process of leukocyte movement from blood into tissues

Question 3

inflammation

Answer 3

the recruitment of leukocytes and plasma proteins form the blood to sites of infection and tissue injury

triggered by recognition of microbes and dead tissues (innate) and prolonged and refined in adaptive immunity

Question 4

Selectins

Answer 4

Plasma membrane carbohydrate-binding adhesion molecules that mediate an initial step of low-affinity adhesion of circulating leukocytes to endothelial cells lining postcapillary venues

Question 5

location of selectin ligand

Answer 5

on leukocyte

Question 6

location of selectin

Answer 6

endothelial cell

Question 7

P-selectin

Answer 7

(CD62P)
stored in cytoplasmic granules of endothelial cells

rapidly redistributed to the surface in response to:
microbial products
cytokines
histamine from mast cells
thrombin (during coagulation)

Question 8

E-Selectin

Answer 8

(CD62E)

synthesized and expressed on the endothelial cell surface within 1-2 hours in response to the cytokines IL-1, TNF, LPS

Question 9

L-Selectin

Answer 9

A selectin expressed on leukocytes but not on endothelial cells

L-selectin on neutrophils serves to bind these cells to endothelial cells that are activated by IL-1, TNF and other cytokines

Question 10

Integrins

Answer 10

heterodimeric cell surface proteins

composed on two noncovalently linked polypeptide chains

mediate adhesions of cells to other cells or to ECM through specific binding interactions with various ligands

Question 11

LFA-1

Answer 11

integrin expressed on leukocytes

early neutrophils

ligand is ICAM-1

Question 12

VLA-4

Answer 12

integrin expressed on leukocytes

monocytes

ligand is VCAM-1 which is expressed on cytokine activated endothelial cells in some tissues

this interaction is important for leukocyte recruitment into inflammatory sites

Question 13

ICAM-1

Answer 13

ligand for LFA-1 (integrin)

this is a membrane glycoprotein expressed on cytokine-activated endothelial cells and lymphocytes, dendritic cells, magrophages, fibroblasts, and keratinocytes

important in leukocyte-endothelial interactions

Question 14

Activation

Answer 14

important feature of integrins. Their ability to respond to intracellular signals by rapidly increasing their affinity for their ligands

Question 15

Chemokine receptor signalling

Answer 15

if a leukocyte comes close to endothelial cells such as when selectin-dependent rolling of leukoctyes occurs, then chemokines on endothelial surface can bind chemokine receptors on leukocytes

this activates leukocyte integrins increasing their affinity for their ligands on the endothelial cells

chemokines also induce integrin clustering leading to tighter binding of the leukocytes to the endothelium

Question 16

location of chemokine receptor

Answer 16

leukocytes

Question 17

location of chemokine

Answer 17

endothelial surface

Question 18

chemokines

Answer 18

structurally homologous cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues

Question 19

what type of receptor is a chemokine

Answer 19

G protein coupled receptor

Question 20

CCL2

Answer 20

Chemokine

Major function - Mixed leukocyte recruitment

receptor - CCR2

Original name (MCP-1)

Question 21

CCL7

Answer 21

(MCP -3)

Chemokine receptor - CCR2, CCR2, CCR3

major function - mixed leukocyte recruitment

Question 22

CCL5

Answer 22

(rantes)

chemokine receptor - CCR1, CCR3, CCR5

mixed leukocyte recruitment

Question 23

CXCL8

Answer 23

original name (IL-8)

Chemokine receptor (CXCR1, CXCR2)

Neutrophil recruitment

Question 24

what do chemokines bind to

Answer 24

bind to heparan sulfate proteoglycans on endothelial tissues that line postcapillary venues and are displayed in this way to circulating leukocytes

chemokines then bind to receptors on leukocytes

Question 25

Chemokinesis

Answer 25

extravascular chemokines stimulate movement of leukocytes and their migration toward the chemical gradient of the secrete protein – leukocytes move toward infected cells

Question 26

Steps in migration of leukocytes into tissues

Answer 26

1) Selectin-mediated rolling of leukocytes on endothelium
2) Chemokine-mediated increase in affinity of integrins
3) Stable integrin-mediated adhesion of leukocytes to endothelium due to cytokines (TNF, IL-1) enhancing endothelial expression of integrin ligands
4) Transmigration of leukocytes through the endothelium

Question 27

Paracellular transmigration

Answer 27

leukocytes transmigrate b/w the borders of endothelial cells

Question 28

Transcellular migration

Answer 28

leukocytes move through endothelial cells rather than between them, less understood mechanism