MW L4 Leukocyte Chemotaxis Flashcards

1
Q

4 steps if leukocyte diapedesis

A
  1. circulating
  2. tethering/rolling
  3. firm adhesion
  4. transmigration
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2
Q

What is a leukocyte?

A

WBC

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3
Q

What guides tethering and rolling

A

selectins - specific homing receptors and their ligands

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4
Q

3 types of selectins

what expresses them

A

L (leucocytes)
P (platelets & endothelium)
E (endothelium)

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5
Q

What do L-selectins bind to?

A

Carbohydrates on the endothelium

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6
Q

Which selectins bind leukocytes?

A

P and E

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7
Q

L-selectin activation leads to….(2)

A

transient increase in avidity

rapid shedding by proteolytic cleavage (‘shedase’)

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8
Q

Where is P selectin stored?

When does it translocate to cell surface?

A

In granules

On cell activation (thrombin, histamine)

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9
Q

E selectin expression is induced by ….. (2)

A

cytokines
or
LPS

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10
Q

Expression of E selectin requires

A

de novo synthesis

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11
Q

Glucocorticoid effect on selectins?

A

E selectin is inhibited

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12
Q

LAD II stands for

A

leukocyte adhesion deficiency II

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13
Q

Pts with LAD II have normal ………………… in vitro

A

phagocytosis and respiratory burst

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14
Q

Pts with LAD II have defective …………. metabolism

this causes,,,,

A

fructose

leukocytes do not express selectins

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15
Q

LAD II causes decreased rolling response on ………. or ………

A

E or P selectins

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16
Q

severely impaired ……………………. in skin inflammation with LAD II

A

<90% decreased

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17
Q

Rolling along the endothelial surface activates …………..
where…………

A

Integrins

on the LEUKOCYTE surface

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18
Q

Integrins are …….. proteins

expressed where?

A

heterodimeric

expressed on the surface of leukocytes and most other cells

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19
Q

Integrins have a common ……. chain

A

Beta2 chain

20
Q

There are ………… forms of alpha chain

this means ……… heterodimers are formed

A

3

alpha L /beta 2
alpha M/ beta 2
alpha X/ beta 2

21
Q

Leukocyte adhesion changes avidity and affinity how?

A

Conformational change - affinity

Clustering of integrins - avidity

22
Q

LAD I or II has pus?

A

neither - both have recurrent infections

23
Q

LAD I what do leukocytes do in vitro?

A

they do not adhere to extracellular material

24
Q

ICAM are…

A

intercellular adhesion molecules

25
ICAM-2 is expressed when and where?
basally on the endothelium
26
ICAM-1 is expressed when
induced by cytokines IL-1 and TNF
27
What binds to ICAM
intergrins
28
............ is expressed on eosinophils, monocytes and T cells
alpha4beta1
29
What binds to alpha4beta1?? | What is this induced by?
VCAM-1 (vascular cell adhesion molecule) | cytokines induce
30
Treatment for recurrent MS (and maybe ulcerative colitis)
anti-alpha4 mAb (Natalizumab)
31
problem with anti-alpha4 mAb (Natalizumab)
increase incidence of viral brain infection (progressive multifocal leukoencephalopathy)
32
Improved efficacy of anti-alpha4 mAb (Natalizumab) with ..........
IFN beta
33
CAM pairs in inflammation
Beta 2 and ICAM-1 | Alpha 4 and VCAM-1
34
Chemotaxis is stimulated by....
chemotaxis - no shit.
35
Chemotaxis activate leukocytes causing....
integrin affinity and avidity changes | movement
36
What is the source of the chemotaxis?
site of inflammation - presented to leukocytes - bind to EC surface
37
Non-selective chemotaxins
LTB 4 C3a C5a formyl peptides
38
selective chemotaxins
chemokines | large family of 70-80aa proteins
39
chemokines are produced in response to
IL1, TNF, bacteria
40
What are chemokines?
GPCRs
41
CXC chemokines are found on
Monocytes Resting T cells Dendritic cells Neutrophils (CCL2 are expressed on activated cells and other places WAHHHH)
42
Cells move at different rates, what is fastest?
Neutrophils (acute inflammation) >> monocytes (chronic) > lymphocytes (chronic)
43
How do tissues get selectivity
different selectin and CAM expression | different chemokine expression
44
How do leukocytes get selectiity
different integrin expression | different chemokine receptor expression
45
..... used to tether leukocyte on the endothelium neat the inflammatory site
selectins
46
............. are used for stronger adhesion on chemokine activation of leukocytes
integrins
47
............ are expressed by endothelium and are ligands for integrins
ICAM