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PHAR 510 > CHALK TALKS > Flashcards

CHALK TALKS Flashcards

1
Q

Night-like neutrophils:

A

no CXCR4 therefore released from BM

Increased proteins in granules
Decreased degranulation
Increased NETs

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2
Q

Day-like neutrophils:

A

no selectins therefore can’t reach tissue and remain in circulation

Increased granulation (bc occurs in cytoplasm)
Decreased NETs

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3
Q

Bmal1 deltaN mimics what type of neutrophil? survival?

A

Bmal1 deltaN mimics NIGHT-LIKE –> decreased survival

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4
Q

CXCR4 deltaN mimics what type of neutrophil? survival?

A

CXCR4 deltaN mimics DAY-LIKE –> increased survival

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5
Q

what controls granule content and amount of NETs?

A

Bmal1 and CXCL2/CXCR2 signaling

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6
Q

why must neutrophils be cleared and renewed?

A

to prevent vascular damage

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7
Q

what changes in neutrophils occur during aging and clearance?

A

changes in CD26L and CXCR4

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8
Q

how does CXCR4 affect BM-homing?

A

increased CXCR4 does not increase BM-homing

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9
Q

what are CD26L lo neutrophils phagocytosed by?

A

CD26L lo neutrophils phagocytosed by macrophages

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10
Q

what happens to neutrophil levels with a neutrophil transfer? why?

A

neutrophils increase bc of decreased G-CSF

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11
Q

are signals for HPC egress the same in steady state and inflammation?

A

no –> diff signaling for HPC egress depending on steady state or inflammation

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12
Q

how do macrophages support the hematopoietic niche?

A

producing protein factors

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13
Q

what does neutrophil engulfment trigger?

A

neutrophil engulfment triggers macrophages LXRs

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14
Q

neutrophil is sensor of _______

A

neutrophil is sensor of organism status

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15
Q

neutrophil clearance modulates ________

A

neutrophil clearance modulates non-BM macrophages

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16
Q

what are the main cells that catch bacteria in liver?

A

KCs

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17
Q

what does KC capture of bacteria depend on? what does it not depend on?

A

depends on CRIg but NOT opsonins

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18
Q

what type of bacteria can KCs capture?

A

UNOPSONIZED gram positive bacteria

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19
Q

what part of bacteria do KCs recognize?

A

LTA

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20
Q

what is essential for KCs capturing gram positive bacteria?

A

CRIg-LTA interaction

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21
Q

what type of mice did they use to find that KCs capture bacteria via CRIg?

A

used CR3 KO –> still able to capture bacteria (therefore complement system

used CRIg KO –> cannot capture bacteria, therefore CRIg is responsible

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22
Q

what is CR3?

A

dominant complement receptor for phagocytosis under static conditions on macrophages

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23
Q

at what stage of infection are AMs infected with Tb?

A

EARLY

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24
Q

what happens once AM are infected?

A

move from alveoli to interstitium

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25
Q

what happens once AM are in interstitium?

A

recruits other immune cells to form granuloma and increases proliferation rate to further spread Tb

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26
Q

when do immune cells accumulate in interstitium?

A

BEFORE Tb spreads/before migration

27
Q

what stimulates migration?

A

Tb activates INFLAMMASOME on non-HPCs via ESX secretion system which releases IL1 for MyD88/ILR1 signaling to allow AM to move to interstitium

28
Q

what is BrdU?

A

incorporates into DNA of proliferating cells and can later be tracked and visualized with fluorescent Ab

29
Q

what are CoH mice?

A

pet store mouse crossed with SPF mouse

30
Q

CoH mice and UPEC

A

CoH mice have increased resistance against UPEC –> increased inflammation

31
Q

CoH vs SPF spleens when infected with UPEC

A

both CoH and SPF spleens have increased neutrophils

CoH have increased CD115+ monocytes

32
Q

what is the result of CoH mice having increased CD115+ monocytes?

A

increased survival and clearance

33
Q

what is mAb depletion?

A

Ab binds target on cell of interest and recruits immune killing of that cell

34
Q

Ly6Chi vs Ly6Clo

A

Ly6Chi –> “ready state” + pro-inflammatory

Ly6Clo –> “patroller state” + maintain homeostasis

35
Q

are the CD115+ monocytes in CoH Ly6Chi or Ly6Clo? what is the significance?

A

Ly6Chi –> primed to respond quickly (INNATE TRAINED IMMUNITY)

36
Q

In addition to Ly6Chi, what is found in high levels in CD115+ monocytes?

A

TNFalpha

37
Q

what does BrdU of Ly6Chi CD115+ monocytes show?

A

increased migration of these monocytes from BM in CoH mice and increased myelopoeisis in CoH mice

38
Q

what is the role of pyochelin?

A

made by PA via pqsA to inhibit S. aureus via iron chelation and ROS production

39
Q

how does S. aureus defend against pyochelin?

A

methylates it

40
Q

how was it found that S. aureus methylates pyochelin?

A

MALDI-MS and molecular networking

41
Q

what methylates pyochelin?

A

Spm

42
Q

how was it found that Spm is what methylates pyochelin?

A

library screening of S. aureus mutants and the complementation assay

43
Q

how does methylation of pyochelin affect its function?

A

decreases ROS production and siderophore activity

44
Q

how can you measure siderophore activity?

A

chrome azurol S assay

CAS-Fe + Pch —-> CAS + Pch-Fe
- CAS without Fe is fluorescent

45
Q

3 things that occur in low-iron conditions

A
  1. PA can grow without pyochelin
  2. Pyochelin can REDUCE S. aureus growth
  3. Met-Pch does NOT REDUCE S. aureus growth (bc lost ROS production and siderophore activity)
46
Q

Pch in vivo

A

is Spm is mutated in vivo, S. aureus fitness does decrease but this does not affect the severity of the co-infection with PA

47
Q

how does IAV affect pneumococcal disease?

A

IAV increases suceptibility to pneumococcal disease

48
Q

what is the CRISPR system used to look at pneuomoccal infection?

A

doxycycline-inducible CRISPRi system

49
Q

what does doxycycline do?

A

induces dCas9

50
Q

why is the doxycycline-inducible CRISPRi system good? (2)

A

good for high-throughput quantitative genetic screening

good for mapping infection bottlenecks in mouse model of pneumococcal pneumonia

51
Q

do all mice deal with pneumococcal infection the same?

A

no, even genetically identical mice respond differently

52
Q

which gene reduces pneumococcal virulence when targeted by the CRISPR system?

A

deletion of purA reduced in vivo fitness

53
Q

which genes increase pneumococcal virulence when targeted by the CRISPRi system?

A

deletion of capsule genes promote bacterial viruelnce with IAV superinfection

54
Q

what gene is NOT a good target for CRISPRi system? why?

A

MetK is poor target bc not essential in vivo

55
Q

what allows the HepCCCleaver to enter the cell?

A

plasmid packaged in lipid shell allows entry via MEMBRANE FUSION-MEDIATED INTRACELLULAR TRANSPORT

56
Q

what is membrane fusion independent of (2)?

A
  1. endocytic process
  2. lysosomal process
57
Q

why is the membrane fusion-mediated intracellular transport good?

A

increases delivery efficiency and accessibility to nucleus

58
Q

how do they make the HepCCCleaver specific to the liver?

A

use promoter that increases expression in liver cells

59
Q

how can you sort cells to determine HepCCCleaver liver specificity?

A

sort cells with FACS

60
Q

how do they make the HepCCCleaver specifically TARGET the liver?

A

galactose modification

61
Q

how do they make the HepCCCleaver specifically target HBV viral proteins on the DNA?

A

guide the cleaver with gRNA to target conserved sites –> leads to decreased HBV proteins

62
Q

how do they know that HepCCCleaver can accumulate in the liver?

A

detected increased Cas9 RNA in liver

63
Q

longevity of HepCCCleaver anti-HBV therapeutic effects?

A

has continual anti-HBV therapeutic effects

PHAR 510 (11 decks)

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