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Innate Immunity Flashcards

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1
Q

What is intrinsic innate immunity?

A

Includes APOBEC3G and TRIM5-alpha
Includes proteins that are constitutively expressed and can help to protect the body from infection
They are able to respond immediately
As the response is not induced they cannot tailor their response
Also includes complement- pre-formed pathway

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2
Q

Intrinsic innate immunity is particularly important in protecting against?

A

Retroviral infection

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3
Q

What is induced innate immunity?

A

This is the response that is pathogen induced. The type of PAMPs recognised by PRRs elicits an innate immune response. It is cell-mediated and includes antigen presenting cells such as macrophages and dendritic cells. Also includes phagocytic cells such as neutrophils

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4
Q

APOBEC3G and TRIM5-alpha are?

A

Intrinsic immune proteins

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5
Q

What is the function of APOBEC3G?

A

It is a constitutively expressed cellular protein
It becomes incorporated into the retrovirus virion
When the virus infects a new cell the APOBEC3G protein can cause hypermutation through deamination of C–>U on the minus strand of DNA during reverse transcription. results in G–>A mutation on the plus strand of DNA. This hypermutation prevents the retrovirus from integration and replication .

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6
Q

APOBEC3G interferes with?

A

Reverse transcription

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7
Q

What is the retroviral counter defence to APOBEC3G?

A

Vif

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8
Q

What is Vif?

A

Viral infectivity factor

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9
Q

What does Vif doo?

A

It targets APOBEC3G for degradation

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10
Q

TRIM-5 alpha does what?

A

Prevents viral uncoating and reverse transcription of retroviruses

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11
Q

Is human TRIM-5 alpha effective against HIV?

A

No

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12
Q

What is the theory for why human TRIM-5 alpha is ineffective against HIV?

A

The idea is that human TRIM-5 alpha acquired mutations and evolved to fight PtERV infection. However, as a consequence of these changes we are now more susceptible to HIV infection.

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13
Q

What are some membrane PRRs?

A

TLRs: 1,2,4,5,6

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14
Q

What are some cytoplasmic PRRs?

A

RLRs: MDA-5 and RIG-I
TLRs: 3,7,8,9

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15
Q

What are RLRs?

A

Rig like receptors

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16
Q

What are the two RLRs you must know?

A

MDA-5 and RIG-I

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17
Q

What does MDA-5 recognise?

A

It recognises long dsRNA

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18
Q

What does RIG-I recognise?

A

Short dsRNA with a 5’ triphosphate CAP

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19
Q

RIG-I and MDA-5 signalling?

A

Upon recognition of dsRNA they bind to signalling adaptor MAVS
This leads to IRF-3 and NF-kB production

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20
Q

Another name for MAVS?

A

Cardif

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21
Q

What are the cytoplasmic TLRs?

A

3,7,8,9

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22
Q

What does TLR3 recognise?

A

dsRNA

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23
Q

What do TLRs 7 and 8 recognise?

A

ssRNA

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24
Q

What does TLR 9 recognise?

A

Unmethylated CpG motifs

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25
What are CpG motifs?
When a cytosine is followed by a guanosine in the 5'-3' direction. TLR9 recognises unmethylated CpG motifs.
26
All TLRs except for TLR3 are capable of signalling via which adaptor?
Myd88 dependent pathway
27
TLR4 and TLR3 are capable of the Myd88 independent pathway which involves which adaptor?
TRIF adaptor
28
Signalling via Myd88 activates?
NF-kB
29
How does signalling via Myd88 work?
Recognition of the PAMP Recruitment of Myd88 Recruitment of kinases Kinases phosphorylate IkB NF-kB is released and can enter the nucleus Activates the expression of genes e.g. production of pro-inflammatory molecules
30
What is NF-kB?
It is a protein complex which can enter the nucleus and regulate the transcription of multiple genes
31
What is IkB?
Found bound to NF-kB. It inhibits NF-kB
32
How is IkB released from NF-kB?
Through phosphorylation of IkB by kinases
33
TLR3 signalling?
Myd88 independent TRIF adaptor Activation of IRF-3 and NF-kB
34
First cytokine discovered?
Interferons
35
What are interferons?
Signalling proteins | Cytokines
36
What are the type I interferons?
Alpha and beta
37
Type I interferons are produced by which cells?
Fibroblast
38
Type I interferon function?
- Activate NK cells - Upregulate MHC-I expression - Induce an antiviral state in cells
39
What receptor do type I interferons bind?
IFNAR
40
What is the type II interferon?
IFN-g
41
What cells produce IFN-g?
Th1 cells | NK cells
42
Action of IFN-g?
Activates macrophages- classical activation Increases their microbicidal activity Causes them to increase expression of reactive oxygen and nitrogen intermediates
43
IFN-g binds to which receptor?
IFNGR
44
Which type I interferon is produced first?
IFN-b
45
IFN-a is primarily produced after?
The amplification resposne
46
Which IRF leads to the production of IFN-a?
IRF-7
47
Which IRF leads to the production of IFN-b?
IRF-3
48
Describe the process of interferon amplification?
1. Cell recognises PAMPs via PRRs 2. NF-kB and IRF-3 are produced 3. IFN-beta is produced and released 4. IFN-beta binds to the IFNAR 5. JAK-STAT signalling 6. ISGF3 complex binds to the ISRE and activates ISGs 7. Production of ISG encoded effectors and IRF-7 8. IRF-7 leads to the production of IFN-a
49
What are the Janus kinases involved?
JAK-1 | TYK-2
50
Describe JAK-STAT signalling?
1. Binding of interferon to the receptor 2. Recruitment of STAT-1 and STAT-2 3. Phosphorylation of STAT-1 and STAT-2 4. IRF-9 recruited 5. STAT-1, STAT-2 and IRF-9 form an ISGF3 complex which can enter the nucleus
51
STAT-1, STAT-2 and IRF-9 form which complex?
ISGF3
52
What is ISRE?
Interferon stimulated response element
53
Where is ISRE located?
Within the promoter of ISG
54
ISG?
Interferon stimulated gene
55
ISG encodes which ISG effectors, some examples?
``` Tetherin TRIM-5 alpha APOBEC3G Intimin 1/2/3 PKR OAS ```
56
IRF-3 leads to the production of?
IFN-b
57
IRF-7 leads to the production of?
IFN-a
58
PRRs do not only recongise PAMPs, they are also able to recognise DAMPs which are?
Danger associated molecular patterns
59
Examples of a DAMP?
Cytosolic DNA
60
What is cytosolic DNA recognised by?
cGAS
61
What is cGAS?
Cyclic GMP-AMP synthase
62
When cGAS recognises the cytosolic DNA?
cGAS is activated and causes GTP and ATP to become cyclic GMP-AMP (cGAMP) cGAMP binds and activates STING STING leads to TBK1 kinase which leads to IRF-3 activation/phosphorylation Leads to IFN-b production (production of type I IFN response)
63
IFITM3 ISG has a role in?
Preventing influenza from fusing and leaving late endosomes
64
IFITM1/2/3 have a role in?
Preventing viral entry
65
Role of tetherin?
Prevents retroviruses from infecting new cells, binds retroviruses that bud off
66
OAS stands for?
2'-5' oligoadenylate synthetase
67
What activates OAS?
dsRNA
68
When dsRNA binds to OAS?
Causes activation of RNaseL
69
What does RNaseL do?
Degrades all intracelluar RNA, pathogen and cellular alike | Prevents protein synthesis
70
What is PKR?
Protein Kinase R
71
PKR is activated by?
dsRNA
72
Once PKR binds dsRNA?
Autophosphorylation Can then phosphorylate eIF2 which is needed for initiation of translation Prevents translation from occurring
73
PKR also leads to?
NF-kB activation

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