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Interferons Flashcards

1
Q

What are the three types of interferons?

A

Type 1 = alpha or beta
Type 2 = gamma
Type 3 = lambda

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2
Q

State three functions of IFN alpha or beta

A

Activation of adaptive immune response
Modulation of innate immune response (promotes Ag presentation and promotes NK cells)
Induces antimicrobial state in infected and neighbouring cells

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3
Q

How do type 1 interferons modulate the innate immune response?

A

Promotes Ag presentation

Promotes NK cells

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4
Q

Which cells produce IFN gamma?

A

Activated T cells

Activated NK cells

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5
Q

Which receptor does IFN gamma bind to?

A

IFN gamma receptor

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6
Q

Which tissues are an important target of type 3 interferons?

A

IFN lambda are important on epithelial surfaces

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7
Q

Which receptors do IFN lambda signal though and where are these found?

A

IL 28 receptor
IL 10 beta
Present on epithelial surfaces

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8
Q

Which receptor does IFN beta bind to?

A

IFN alpha receptor

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9
Q

Which cells release IFN beta?

A

Infected cells

Fibroblasts

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10
Q

Which cells produce IFN alpha and which transcription factor is constitutively expressed in these cells?

A

Plasmacytoid dendritic cells

IRF-7

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11
Q

Which type 1 interferon has 13-14 isotypes?

A

IFN ALPHA

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12
Q

List three pattern recognition receptors

A

RIG-1/mda5
TLR
cGAS

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13
Q

What does RIG-1 recognise?

A

RNA lacking CAP

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14
Q

What do TLR recognise?

A

RNA in endosomes

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15
Q

What activates the cGAS enyzme?

A

Cytoplasmic double stranded DNA

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16
Q

Upon recognition of RNA which lacks CAP, what does RIG-1 bind to and activate?

A

RIG-1 binds to mavs

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17
Q

What is the downstream effect of RIG-1 binding to mavs?

A

Activated mavs phosphorylates Irf3

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18
Q

What does phosphorylated Irf3 do?

A

Irf3 dimerises and translocates to the nucleus, where it acts as a transcription factor for IFN-beta

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19
Q

Which RNA pattern recognition receptor pathway joins up with the IRF-3 pathway?

A

TLR3

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20
Q

What are the main two TLR in the endosomes?

A

TLR3

TLR7/8

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21
Q

What is the downstream effect of TLR 3 activation?

A

Phosphorylation of IRF3, dimerization, translocation to the nucleus, and transcription of IFN-beta

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22
Q

Which of the TLR pathways is unique to the plasma cytoid dendritic cells?

A

TLR7/8 pathway

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23
Q

What downstream molecule do activated TLR7/8 signal via?

A

TLR7/8 signal via myd88

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24
Q

What is the effect of signalling via myd88?

A

Downstream phosphorylation of IRF7 (which is constitutively expressed in plasmacytoid dendritic cells)

IRF7 then acts to transcribe IFN alpha and beta

25
What does cGAS produce when activated?
cGAMP
26
What does cGAMP bind to and where does this exist?
Binds to STING on endoplasmic reticulum
27
What does STING do?
Phosphorylates IRF3 via TBK 1
28
What is the downstream effect of IRF 3 dimerisation after STING?
IFN beta production
29
Once IFN beta has been produced, what does it do?
It binds to IFN alpha receptor heterodimers via paracrine signalling
30
What is the downstream result of IFN beta binding to IFN alpha receptors on neighbouring cells? (explain in detail)
Recruitment of JAK Phosphorylation of STAT Translocation of STAT to the nucleus Transcription of ISG (interferon stimulated genes)
31
List seven interferon stimulated genes
``` IFITM3 ADAR PKR 2'5 OAS Mx Serpine Viperin ```
32
What does the interferon stimulated gene, PKR, do?
Inhibits translation so that viruses can't translate their proteins
33
What does the interferon stimulated gene, ADAR, do?
It induces errors during viral replication
34
What does the interferon stimulated gene, IFITM3, do?
Restricts viral enclosed endosomes from changing shape and releasing the virus
35
What does the interferon stimulated gene, Mx, do?
Inhibits incoming viral genomes by wrapping around nucleocapsids of incoming viruses
36
What are the two classes of Mx and which diseases do they inhibit?
Mx 1 - inhibit influenza | Mx 2 - inhibits HIV
37
What does the interferon stimulated gene, 2'5OAS, do?
Activates RNAse L to destroy single stranded RNA
38
What does the interferon stimulated gene, Serpine, do?
Activates proteases
39
What does the interferon stimulated gene, Viperin, do?
Inhibits viral budding
40
What molecule is produced to regulate ISG and limit damage?
SOCS; suppressors of cytokine signalling
41
List seven ways in which viruses evade the interferon response
Hide PAMP Inhibit IFN signalling Block IFN induction cascades by destroying/binding Block individual IFN-induced antiviral enzymes Activate SOCS Interfere with host cell gene expression and block protein synthesis Replication strategy may be insensitive to IFN
42
Give an example of how Hep C avoids the IFN response
Produces NS3/4; this is a protease which cleaves MAVS away from the mitochondrial membrane
43
Give an example of how influenza avoids the IFN response
NS1 binds to RIG-1 and prevents it from recognising RNA (antagonises it) It also inhibits nuclear processing of newly synthesised genes (prevents transcription)
44
List two DNA viruses
Pox virus | Herpes virus
45
What is special about DNA viruses?
They have such a large genome that they have space to encode 'accessory genes' which enhance the survival of the virus (note accessory genes are not essential for survival)
46
Give an example of an accessory gene produced by Pox virus
Vaccinia virus B18 is a SOLUBLE CYTOKINE RECEPTOR produced by Pox virus to mop up interferons
47
Name three products produced by Ebola to avoid the IFN response
VP35 VP30 VP24
48
What does VP24 do?
Blocks downstream signalling of IFNs to neighbouring cells
49
What does VP30 do?
Blocks RNAi (RNA interference inhibits gene expression or translation)
50
What does VP35 do?
Blocks RIG-1/mda5 and RNAi
51
What is the result of too much interferon production but inadequate clearance of the virus/viral interference with the interferon response?
CYTOKINE STORM
52
Which cytokines are mediators of the cytokine storm?
TNF alpha IL1 IL6
53
Give three pathological outcomes of a cytokine storm
``` Pulmonary fibrosis (hence respiratory distress syndrome) Exaggerated inflammatory responses Endothelial dysfunction ```
54
List three infections where a cytokine storm results in a worse pathology
Dengue haemorrhagic fever Severe influenza Ebola
55
What was the rationale behind using IFN as an antiviral treatment? Which virus was this type of therapy used against?
Patients feel worse after IFN treatment therefore not used Was once used against Hep C
56
Which type of interferon could potentially be given, which will produce a local response?
IFN lambda (only affects epithelial surfaces whereas IFN a/b would affect all cells)
57
How could the knowledge of IFN resistance be used in vaccines?
Viruses could be genetically engineered to not have interferon avoiding genes, thereby producing attenuated strains to be used in a vaccine.
58
What is the rationale behind oncolytic viruses?
Cancer cells are not very good at producing interferon responses, therefore viruses can kill cancer cells. Since healthy cells can produce interferons and can clear the virus, they will not be affected by oncolytic viruses.

Microbiology (8 decks)

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