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Infect & Immune 1 JAL & MW > MW L4 Leukocyte Chemotaxis > Flashcards

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
Q

ICAM-2 is expressed when and where?

A

basally on the endothelium

26
Q

ICAM-1 is expressed when

A

induced by cytokines IL-1 and TNF

27
Q

What binds to ICAM

A

intergrins

28
Q

………… is expressed on eosinophils, monocytes and T cells

A

alpha4beta1

29
Q

What binds to alpha4beta1??

What is this induced by?

A

VCAM-1 (vascular cell adhesion molecule)

cytokines induce

30
Q

Treatment for recurrent MS (and maybe ulcerative colitis)

A

anti-alpha4 mAb (Natalizumab)

31
Q

problem with anti-alpha4 mAb (Natalizumab)

A

increase incidence of viral brain infection (progressive multifocal leukoencephalopathy)

32
Q

Improved efficacy of anti-alpha4 mAb (Natalizumab) with ……….

A

IFN beta

33
Q

CAM pairs in inflammation

A

Beta 2 and ICAM-1

Alpha 4 and VCAM-1

34
Q

Chemotaxis is stimulated by….

A

chemotaxis - no shit.

35
Q

Chemotaxis activate leukocytes causing….

A

integrin affinity and avidity changes

movement

36
Q

What is the source of the chemotaxis?

A

site of inflammation - presented to leukocytes - bind to EC surface

37
Q

Non-selective chemotaxins

A

LTB 4
C3a C5a
formyl peptides

38
Q

selective chemotaxins

A

chemokines

large family of 70-80aa proteins

39
Q

chemokines are produced in response to

A

IL1, TNF, bacteria

40
Q

What are chemokines?

A

GPCRs

41
Q

CXC chemokines are found on

A

Monocytes
Resting T cells
Dendritic cells
Neutrophils

(CCL2 are expressed on activated cells and other places WAHHHH)

42
Q

Cells move at different rates, what is fastest?

A

Neutrophils (acute inflammation)&raquo_space; monocytes (chronic) > lymphocytes (chronic)

43
Q

How do tissues get selectivity

A

different selectin and CAM expression

different chemokine expression

44
Q

How do leukocytes get selectiity

A

different integrin expression

different chemokine receptor expression

45
Q

….. used to tether leukocyte on the endothelium neat the inflammatory site

A

selectins

46
Q

…………. are used for stronger adhesion on chemokine activation of leukocytes

A

integrins

47
Q

………… are expressed by endothelium and are ligands for integrins

A

ICAM

Infect & Immune 1 JAL & MW (12 decks)

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