Imaging the Immune System in vivo Flashcards

1
Q

What techniques have been used to allow dynamic imaging of the immune cells in many tissues?

A

confocal and 2 photon microscopy intrsuments with new surgical methods and fluorscent labeling of cells

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2
Q

What is the main advantge of two-photon imaging?

A

gives ability to image depp into live tissues

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3
Q

What are the 3 structural families of adhesion molecules important for leukocyte recruitment?

A

selectins; integrins; Ig superfamily e.g ICAM

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4
Q

What do selectins bind?

A

carbohydrates

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5
Q

What is the function of selectins?

A

intiate leukocyte-endothelial interaction

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6
Q

What are hte selectins expressed on endothelium?

A

P and E selectins

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7
Q

what is hte ligand for P and E selectins?

A

sialyl-Lewisx

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8
Q

What do integrins bind?

A

cell-adhesion moleculesand ECM

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9
Q

give an example of an integrin?

A

LFA-1

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10
Q

Give an exmple of a ligand of LFA-1?

A

ICAM-1

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11
Q

What is the function of integrins?

A

strong adhesion

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12
Q

What cells is ICAM-1 found on?

A

activated endothelium and activated leukocytes

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13
Q

Waht type of protein are selectins?

A

glycoproteins

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14
Q

What is found on the extracellular domain of ICAMs?

A

several Ig-like domains

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15
Q

What is the structure of an integrin molecule?

A

2 transmebrane protein chains alpha and beta

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16
Q

What other name is LFA-1 known as?

A

CD11a/CD18

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17
Q

What other name is CR3 known as?

A

CD11b/CD18

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18
Q

What may monocytes use to navigate out of hte blood vessel in the absence of infection?

A

ICAM-2 (expressed on resting endothelium)

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19
Q

What promotes strong adhesion between leukocytes and endothelial cells?

A

induction of ICAM-1 on activated endothelium and conformation change in LFA-1 and CR3

20
Q

What is the function of integrins having an active and inactive state?

A

cells can make and break integrin0mediated adhesions in repsonse to signals received via the integrin or other receptors

21
Q

What is the integrin molecule linked to the actin cytoskeleton when activated?

A

talin

22
Q

What is the function of talin?

A

chemokines generate intracellular signals that cause talin to the cytoplasmic tails of the beta chain of LFA-1 and CR3 forcing the extracellular region to become activated

23
Q

What cytokine is especially important in activating endothelium?

A

TNF-a

24
Q

how does TNF-a cause the appearnce of P-selectin?

A

induces the rapid externalisation of granules called Weibel-Palade bodies

25
Q

How is E-selectin expresed on endothelial cells?

A

when P-selectin gets to the surface, mRNA encoding E-selectin is synthesis

26
Q

What is the prominent leukocyte integrin on DCs?

A

CD11c:CD18 or CR4

27
Q

How does the dilation of blood vessels initiate extravasation?

A

slower blood flow with dilation allowing leukocytes to interact with the vascular endothelium

28
Q

What is the first stage of extravasation?

A

induction of selectins induces leukocyte rolling

29
Q

What signals induce P-selectin appearance?

A

LT-B4; C5a; histamine; TNF-a and LPS

30
Q

What allows shear-resistant rolling by neutrophils?

A

long extensions of plasma membrane-slings which bind the endothelium and wrap around the cell as it rolls

31
Q

What is shear-resistant rolling?

A

rolling along the endothelium at high flow rates

32
Q

What induces the presence of ICAM-1?

A

TNF-a

33
Q

What happesn when LFA-1 and CR3 are activated?

A

causes arrest of rolling

34
Q

What further adhesive interactions does extravasation require?

A

PECAM/CD31

35
Q

What cells is PECAM expressed on?

A

both the leukocyte and intercellular junctions between endothelial cells

36
Q

How does the leukocyte penetrate the basement membrane of hte nedothelium?

A

aid of enzymes that break down the ECM

37
Q

What is hte movement thourhg the basement membrane known as?

A

diapedesis

38
Q

What chemokine is reelased by macrophages that first encounter pathogens?

A

CXCL8

39
Q

What is the function of CXCL8 produced by macrophages?

A

recruits neutrophils

40
Q

What chemokine recruits monocytes?

A

CCL2

41
Q

What enzyme do neutrophils use to break down the BM?

A

metalloproteinase enzyme: MMP-9

42
Q

What happens in chronic inflammatory disease?

A

pimrary pathophysiology releases DAMPs which result in a low grade inflammatory reponse

43
Q

Why does atherosclerosis typically happen at bifurcations?

A

turbulent velocity stimulates immune repsonse

44
Q

How do cells udergo extravasation via transcellular route?

A

by punching holes in the endothelial cell

45
Q

How do you mark a sepcific cell with fluoresence?

A

put fluorescence gene after promotor of a gene you know is over-expressed in a prticular cell type

46
Q

What is the differenceb etween the excitation vs emission wavelengths known as?

A

Stoke’s shigt