Cell Migration Flashcards

(55 cards)

1
Q

What are the three types of selectins?

A

E-selectin, P-selectin, L-selectin

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2
Q

Where is E-selectin expressed and what is its function?

A

Expressed on activated endothelial cells; mediates rolling of leukocytes.

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3
Q

Where is P-selectin found and what does it do?

A

Found on endothelial cells and platelets; initiates leukocyte rolling.

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4
Q

What cells express L-selectin?

A

Naive T cells, B cells, and neutrophils.

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5
Q

What is the role of L-selectin in lymphocyte trafficking?

A

Mediates homing to lymph nodes via high endothelial venules (HEVs).

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6
Q

What do selectins bind to?

A

Selectins bind to specific carbohydrate ligands like sialyl Lewis X on leukocytes.

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7
Q

What are chemokines?

A

Chemotactic cytokines that direct the migration of immune cells.

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8
Q

What is chemotaxis?

A

The movement of leukocytes toward the source of chemokines follows the concentration gradient

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9
Q

What are the major families of chemokines?

A

CC, CXC, C, and CX3C based on cysteine patterns.

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10
Q

Which chemokines attract neutrophils?

A

CXC chemokines with ELR motifs, e.g., CXCL8 (IL-8).

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11
Q

Which cells produce chemokines?

A

Leukocytes, endothelial cells, epithelial cells, fibroblasts.

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12
Q

What induces chemokine production?

A

Microbial recognition and inflammatory cytokines like TNF, IL-1, and IL-17.

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13
Q

What type of receptors are chemokine receptors?

A

G-protein-coupled receptors (GPCRs).

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14
Q

What is the DRYLAIV motif?

A

A sequence in chemokine receptors essential for G protein signaling.

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15
Q

What happens when chemokine receptors are activated?

A

Trigger actin polymerization and integrin activation for cell movement.

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16
Q

Which chemokine receptors are HIV coreceptors?

A

CCR5 and CXCR4.

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17
Q

What are atypical chemokine receptors (ACKRs)?

A

Receptors that regulate or scavenge chemokines without activating G-protein signaling.

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18
Q

Where is ACKR1 found?

A

On erythrocytes and postcapillary venule endothelium.

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19
Q

What are integrins?

A

Adhesion molecules on leukocytes that mediate firm adhesion.

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20
Q

What triggers integrin activation?

A

Signals from chemokine receptors.

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21
Q

What are examples of integrins?

A

LFA-1 (CD11a/CD18) and VLA-4 (α4β1).

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22
Q

What do integrins bind to?

A

ICAM-1 and VCAM-1 on endothelial cells.

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23
Q

What is the role of integrins in leukocyte trafficking?

A

Enable firm adhesion of leukocytes to endothelium before migration.

24
Q

Where are ICAM-1 and VCAM-1 found?

A

On activated endothelial cells.

25
What is the function of ICAM-1?
Ligand for LFA-1 on leukocytes.
26
What is the function of VCAM-1?
Ligand for VLA-4 on lymphocytes and monocytes.
27
What are the four steps of leukocyte extravasation?
Rolling, activation, adhesion, and transmigration.
28
Which molecules mediate rolling?
Selectins and their ligands.
29
Which molecules are responsible for activation?
Chemokines and chemokine receptors.
30
Which molecules are responsible for adhesion?
Integrins and their ligands.
31
Where does transmigration occur?
Between endothelial cells into tissue, guided by chemokines.
32
What is the first step of leukocyte recruitment?
Selectin-mediated rolling on endothelium
33
Which selectins are involved in leukocyte rolling?
E-selectin and P-selectin
34
What induces E-selectin expression on endothelial cells?
Cytokines TNF and IL-1
35
What induces P-selectin expression on endothelial cells?
Histamine from mast cells and thrombin
36
What is margination?
The process where leukocytes move to the periphery of blood flow near the endothelium
37
Why do leukocytes roll along the endothelium?
Due to low-affinity interactions between selectins and their ligands
38
What is the second step of leukocyte recruitment?
Chemokine-mediated activation of integrins
39
What happens during chemokine-mediated activation?
Chemokines bind to leukocyte receptors, increasing integrin affinity
40
What is the third step of leukocyte recruitment?
Stable integrin-mediated arrest on endothelium
41
Which integrins are involved in firm adhesion?
LFA-1, MAC-1, and VLA-4
42
What are the ligands for leukocyte integrins?
ICAM-1 for LFA-1 and MAC-1, VCAM-1 for VLA-4
43
How do integrins achieve high-affinity binding?
Via conformational change triggered by chemokine signaling
44
What is the fourth step of leukocyte recruitment?
Transmigration (diapedesis)
45
What is paracellular transmigration?
Leukocytes move between endothelial cells
46
What molecule facilitates transmigration?
CD31 (PECAM-1)
47
What complex must be disrupted for transmigration to occur?
VE-cadherin adherens junction complex
48
What does VE-cadherin do?
Maintains adherens junctions between endothelial cells
49
What is the role of ICAM-1?
Ligand for LFA-1 and MAC-1 integrins on leukocytes
50
What is the role of VCAM-1?
Ligand for VLA-4 integrin on leukocytes
51
How does blood flow change during inflammation?
Blood vessels dilate and flow slows, promoting leukocyte margination
52
What is the function of chemokines in leukocyte recruitment?
They activate leukocyte integrins for firm adhesion
53
Where are selectins expressed?
On endothelial cells during inflammation
54
Where are integrins expressed?
On leukocytes
55
What is transcellular migration?
Rare process where leukocytes pass through endothelial cells