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MM4 Innate immunity Flashcards

1
Q

What falls under intrinsic immunity?

A

Complement
APOBEC3G
TRIM5 alpha

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2
Q

What is innate immunity?

A

The induced cell mediated response to infection. The main function of innate immunity is to prime the acquired immune response

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3
Q

How does APOBEC3G work?

A

It works by causing deamination of C–>U on the -ssDNA during reverse transcription of +ssRNA
Causes G–>A hypermutation on the +ssDNA strand
Destroys the coding and replicative capacity of the virus

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4
Q

Counter defence of HIV to APOBEC3G?

A

Vif
Viral infectivity factor
Targets the APOBEC3G for degradation

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5
Q

How does TRIM5 alpha function?

A

It functions by recognising viral retroviral capsids and preventing uncoating and reverse transcription

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6
Q

Why can human TRIM5 alpha not protect against HIV?

A

Thought that human TRIM5 alpha evolved in response to a PtERV infection 4 million years ago. The human TRIM5 alpha developed mutations to better prevent against PtERV infection. This has now made humans susceptible to HIV infection- cannot be a master of all.

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7
Q

What cell surface receptor TLRs are there?

A

TLR 2,4,5,6

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8
Q

What does TLR2 recognise?

A

Gram positive bacteria
Lipoprotein
Lipomannan LM
Lipoarabinomannan LAM

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9
Q

What does TLR5 recognise?

A

Bacterial flagellin

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10
Q

What does TRL4 recognise?

A

Gram negative bacteria

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11
Q

What cytoplasmic receptors must you know?

A

TLR 3,7,8,9
RIG-I like receptors:
RIG-I and MDA-5

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12
Q

What does TLR3 recognise?

A

dsRNA

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13
Q

What do TLR7 and TLR8 recognise?

A

ssRNA

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14
Q

What does TLR9 recognise?

A

CpG motifs
This is where a cytosine nucleotide is directly followed by a guanine nucleotide
5’-C-phosphate-G-3’
Unmethylated CpG motifs are not common in vertebrates and are indicative of viral infection

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15
Q

What doe RIG-I recognise?

A

Short dsRNA with 5’ triphosphate caps

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16
Q

What does MDA-5 recognise?

A

Long dsRNA

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17
Q

How do RLRs signal?

A

Via the Cardif/MAVs adaptors

Then leads to NFkB and IRF-3 production

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18
Q

All TLRs apart from TLR3 signal via which adaptor?

A

Myd88

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19
Q

TLR3 signals via?

A

TRIF adaptor

In the Myd88 independent pathway

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20
Q

TLR4 is capable of what signalling?

A

Both Myd88 dependent and independent signalling

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21
Q

IRF-3 leads to production of which interferon?

A

IFN-b

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22
Q

IRF-7 leads to the production of which interferon?

A

IFN-a

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23
Q

What is NF-kB?

A

It is a complex which is able to enter the nucleus and initiate transcription of many genes. It often leads to the production of pro-inflammatory cytokines

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24
Q

What prevents NF-kB entering the nucleus?

25
What needs to happen to IkB to allow NF-kB activation?
Phosphorylation and degradation of IkB
26
What are interferons?
The first cytokines identified Proteins Signalling molecules
27
Type I interferons are produced by?
Fibroblast cells
28
Type I interferons bind to which receptors?
IFNAR
29
Type I interferons include?
IFN-a | IFN-b
30
Type I interferons cause what?
- Antiviral state to be induced in neighbouring cells - Up-regulation of MHC-I on cells - NK cell activation
31
How many types of IFN-a and IFN-b?
14 IFN-a | 1 IFN-b
32
Type II interferons bind to which receptors?
IFNGR
33
Type II interferons include?
IFN-g
34
Type II interferons are produced by?
Th1 T cells | NK cells
35
What do type II interferons do?
Lead to classical macrophage activation Increased lysosomal activity of macrophages Up-regulates their microbicidal activity Causes macrophages to produce reactive oxygen and nitrogen species. Oxygen is needed for ROS L-arginine is needed for RNS
36
How is L-arginine transformed into nitric oxide?
Via iNOS | Inducible nitric oxid synthase
37
Which interferon is primarily produced before the amplification response?
IFN-b
38
Which interferon is primarily produced after the amplification response?
IFN-a
39
Describe interferon amplification?
``` IFN-b binds to IFNAR JAK-STAT signalling TYK-2 and JAK-1 phosphorylate STAT-1 and STAT-2 They form a complex with IRF-9 Complex is known as ISGF3 This enters the nucleus and binds to the ISRE ISG is activated IRF-7 --> IFN-a IRF-3 --> IFN-b ```
40
What leads to phosphorylated STAT-1 and STAT-2?
TYK-2 and JAK-1 Janus kinases
41
What is the ISGF3?
Interferon Stimulated Gene Factor 3
42
What is the ISGF3 composed of?
STAT-1 STAT-2 IRF-9
43
ISGF binds to ISRE which is?
Interferon Stimulated Response Element which is found within the promoter regions of ISGs= Interferon Stimulated Genes
44
ISG encoded products include?
``` Tetherin TRIM5 alpha APOBEC3G OAS= 2'-5' Oligoadenylate synthetase PKR IFITM1/2/3 ```
45
What does tetherin do?
Binds retroviruses to prevent them escaping the cell and infecting new cells
46
What is OAS?
2'-5'- Oligoadenylate synthetase
47
What is PKR?
Protein Kinase R
48
IFITM3?
Present in the late endosome and can prevent fusion of influenza viruses
49
How does OAS work?
Recognises dsRNA Leads to RNaseL production All cellular RNA is degraded including host
50
OAS and PKR are both?
Interferon induced
51
PKR is induced by?
Interferon
52
PKR recognises?
dsRNA
53
How does PKR work?
``` Recognises dsRNA Autophosphorylation into active PKR Can phosphorylate eIF2-a Prevents it from working Translation is halted Also leads to NF-kB activation ```
54
How is cytosolic DNA recognised by?
cGAS
55
What is cGAS?
Cyclic GMP-AMP synthase
56
cGAS recognition of cytosolic DNA leads to?
GTP--> GMP ATP --> AMP cGAMP production: cyclic GMP-AMP
57
cGAMP leads to?
STING activation
58
STING leads to?
TBK1 recruitment
59
What does TBK1 do?
Phosphorylates and activates IRF-3

MM- Viruses (13 decks)

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