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CSB331 > L19: Leukocyte migration > Flashcards

L19: Leukocyte migration Flashcards

1
Q

What are CAMs?

A

Cell adhesion molecules that are on epithelial tissues

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2
Q

What structure is responsible for initial attachment of leukocytes to endothelial cells?

A

selectins

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3
Q

Describe selectin structure. Where is it found. What does it bind to?

A

Has a lectin domain. Found on epithelial tissues. CHO domains on mucins

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4
Q

What are mucins? What do they bind to? Where are they found?

A

glycosylated proteins.
Binds to selectins and other mucins
Found on leukocytes

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5
Q

What are integrins?

A

Heterodimer proteins found in leukocytes.

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6
Q

What are ICAMs? What do they bind to?

A

CAMs with IG domain. Binds to integrins

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7
Q

What are madCAMs? Where are they found? What do they bind to?

A

CAMs with IG and mucin domains. Found in mucosal endothelial. Binds to integrins on lymphocytes

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8
Q

What is tethering and rolling mediated by?

A

Selectins

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9
Q

Selectin binding requires what?

A

Ca2+

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10
Q

What could possibly be pulling leukocytes towards farther epithelial cells during rolling?

A

A whip like throw of actin filament

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11
Q

Are selectins specific to carbohydrate types?

A

Yes they are very selective.

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12
Q

Do epi cells always produce E-selectins? If not, what triggers them?

A

No. Cytokines

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13
Q

What is a type of sugar selectins bind to? Where is this found. How many carbons does it have?

A

Sialyl Lewis X. End of glycoproteins or glycolipids. It is a 9 carbon monosaccharide

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14
Q

How can we see leukocyte movement in blood vessel?

A

Intravital microscopy. Cut blood vessels out of mice. ew.

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15
Q

How do integrins form various types of specificity?

A

Multiple alpha and beta subunits combination

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16
Q

Which Beta subunit is responsible for leukocyte and epithelial cell adhesion? Which alpha unit does it bind with? What is this named?

A

β4. αL. LFA-1

17
Q

Is the sialyl lewis X sugar binding to E selectin a tight bound?

A

No. It unbinds every so often to allow rolling instead of a tight adhesion.

18
Q

What are two types of signalling in integrin activation? Which one is important in leukocyte migration?

A 
Inside out (talin) >> important for leukocyte migration
outside in (fibronogen)
19
Q

Describe inside out integrin activation.

A

Talin binds to intracellular subunits and separates them. This conformational change (flailing out of extracellular domain) allows stronger ligand binding

20
Q

How can we check that inside out activation of integrin is essential?

A

Truncate cytoplasmic tail to disallow inside out signalling and see what happens

21
Q

What can increase activation of talin in leukocyte LFA1 pathway?

A

IL8

22
Q

What are two types of CAM? Which has homotypic and heterotyopic binding?

A

N-CAM (homo) and I-CAM (hetero)

23
Q

Are CAMs Ca2+ depended?

A

No

24
Q

Tight adhesion is done by which two mechanisms?

A

I-CAM + LFA1

IL8 + IL8R

25
Q

IL8R is on the leukocyte or the epi cell?

A

leukocyte

26
Q

What are two types of diapedesis?

A

Paracellular.

Transcellular

27
Q

Which molecule is responsible for paracellular diapedesis? What is it normally a part of?

A

Jam-1. Tight junction

28
Q

What happens in the absence of Jam-1?

A

No paracellular diapedesis

29
Q

Is transcellular diapedesis due to physical or chemical change?

A

Mostly physical. But chemical changes happen in response to the physical interactions.

30
Q

Describe the effects and pathways in epi cells when leukocytes dock on epi cells.

A

NPF > Arp2/3 > actin poly
PIP2 > Cdc42 > Arp2/3
WAVE2 > Arp2/3

31
Q

What happens in the absence of WAVE2?

A

fewer transcellular diapedesis

32
Q

How do leukocytes look for the easiest way for entry during transcellular diapedesis?

A

Yes. They probe with invadopodia like protrusions

33
Q

How do MMPs help in crossing the basal membrane?

A

MMPs are not needed. Somehow these cells can pass right through. Cancer cells do the same

CSB331 (10 decks)

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