Microbiology 1: Interferon Flashcards

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1
Q

Define “interferon”

A

Soluble cytokine produced when cells are exposed to a virus that stimulates de novo transcription of IF-stimulated genes to cause a cytokine storm

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2
Q

What is the general stimulus for IFN production?

A

PAMP recognition

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3
Q

What element of a virus acts as a PAMP?

A

Viral nucleic acid

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4
Q

What sort of PRR is found in the cytoplasm?

A

Rig-1 like receptors (RLRs)

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5
Q

What sort of PRR is found in endosomes?

A

Toll-like receptors (TLRs)

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6
Q

Recall the site of production of each subtype of type 1 IFN

A
IFN-alpha = plasmacytoid dendritic cells
IFN-beta = all cells
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7
Q

Recall the TF that leads to the production of each of the subtypes of type 1 IFN

A
Alpha = IRF7
Beta = IRF3
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8
Q

Where is the IFN-alpha receptor present?

A

All tissues

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9
Q

Describe the structure of the IFNAR

A

Heterodimer

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10
Q

Through which receptor does each of the subtypes of tye 1 IFN signal?

A

IFNAR

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11
Q

Which type of IFN is always first to be made?

A

Type 1 IFN Beta

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12
Q

What is the function of IFN beta?

A

Indices anti-viral state i neighbouring cells

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13
Q

Recall the 3 major functions of type 1 IFN

A

Induce antimicrobial state
Modulate innate immunity
Activate adaptive immunity

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14
Q

How many isotypes are there of each of the subtypes of tye 1 IFN?

A

IFN alpha has 13

IFN beta has 1

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15
Q

What type of IFN is type2 IFN?

A

IFN gamma

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16
Q

Through which receptor does IFN gamma signal?

A

IFNGR

17
Q

By what sort of cells is IFN gamma produced?

A

T cells

NK cells

18
Q

What type of IFN is type 3 IFN?

A

IFN lambda

19
Q

Through which receptors does IFN lambda signal?

A

IL28R amd IL10-beta

20
Q

Where are IFN-lambda receptors expressed?

A

Epithelia

21
Q

What is the main function of IFN lambda?

A

Protect barriers of body - especially important in liver defence against Hep B/C

22
Q

Recall the pathway that leads to the transcription of IFN alpha in the presence of RNA viruses

A
  1. Virus enters endosome in cell
  2. PAMP recognition by TLR in endosome
  3. IFNalpha gene switched on
23
Q

Recall a protective factor that cells may express against influenza virus?

A

IFITM3

24
Q

What is IFITM3?

A

Prevents virus releasing its genome into the next cell

25
Q

Recall the pathway that leads to the transcription of IFN beta in the presence of RNA viruses

A
  1. RNA recognised by RLR in cytoplasm
  2. RIG-1 signalls thorugh MAVS on mitochondrion
  3. IRF3 expressed –> transcription of IFN beta gene
26
Q

Recall the steps of IFN transcription initiated by DNA viruses

A
  1. Sensed in nucleus by cGAS
  2. cGAS –> cGAMP
  3. Sting activated
  4. IFN beta produced
27
Q

What is the main moderator of the IFN response?

A

SOCS

28
Q

What does SOCS stand for?

A

Suppressor Of Cytokine Signalling genes

29
Q

Recall 4 examples of ISGs

A

PKR
2’5’OAS
Mx
ASAR

30
Q

What is the function of the protein encoded by PKR?

A

Inhibition of translation (cell’s “altruistic” response)

31
Q

What is the function of the protein encoded by Mx?

A

Mx1 inhibits influenza genome

Mx2 inhibits HIV genome

32
Q

Recall 5 mechanisms of viral evasion of IFN response

A
  1. SOCS switched on rapidly
  2. PAMP concealed
  3. Rapid replication to outpace response
  4. IFN blockade
  5. Gene expression change
33
Q

How does Hep C evade the viral response?

A

Produces NS3/4 which can cleave MAVS

34
Q

How does H1N1 flu evade the T1 IFN response?

A

Binds RIG-1

35
Q

How does Ebola evade the T1 IFN response?

A

Produces VP proteins that block RIG1 and STAT

36
Q

Recall 3 RNA viruses that can specifically evade T1 IFN

A

Hep C
Ebola
H1N1 flu

37
Q

How do DNA viruses tend to evade the T1 IFN response? Give an example of a virus that does this

A

Encode soluble cytokine receptors to “mop up” IFN eg POX VIRUSES

38
Q

Recall 4 hopes for therapies utilising IFN

A
  1. Mimick Pox virus - produce soluble cytokines
  2. IFN lambda as an antiviral
  3. Live attenuated vaccines using viruses that are unable to control IFN
  4. May be used to treat cancer
39
Q

Recall the immediate downstream signalling pathway of IFN receptors

A

Dimerise to activate STAT