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MM- Viruses > MM4 Innate immunity > Flashcards

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?

A

IkB

25
Q

What needs to happen to IkB to allow NF-kB activation?

A

Phosphorylation and degradation of IkB

26
Q

What are interferons?

A

The first cytokines identified
Proteins
Signalling molecules

27
Q

Type I interferons are produced by?

A

Fibroblast cells

28
Q

Type I interferons bind to which receptors?

A

IFNAR

29
Q

Type I interferons include?

A

IFN-a

IFN-b

30
Q

Type I interferons cause what?

A
  • Antiviral state to be induced in neighbouring cells
  • Up-regulation of MHC-I on cells
  • NK cell activation
31
Q

How many types of IFN-a and IFN-b?

A

14 IFN-a

1 IFN-b

32
Q

Type II interferons bind to which receptors?

A

IFNGR

33
Q

Type II interferons include?

A

IFN-g

34
Q

Type II interferons are produced by?

A

Th1 T cells

NK cells

35
Q

What do type II interferons do?

A

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
Q

How is L-arginine transformed into nitric oxide?

A

Via iNOS

Inducible nitric oxid synthase

37
Q

Which interferon is primarily produced before the amplification response?

A

IFN-b

38
Q

Which interferon is primarily produced after the amplification response?

A

IFN-a

39
Q

Describe interferon amplification?

A 
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
Q

What leads to phosphorylated STAT-1 and STAT-2?

A

TYK-2 and JAK-1 Janus kinases

41
Q

What is the ISGF3?

A

Interferon Stimulated Gene Factor 3

42
Q

What is the ISGF3 composed of?

A

STAT-1
STAT-2
IRF-9

43
Q

ISGF binds to ISRE which is?

A

Interferon Stimulated Response Element which is found within the promoter regions of ISGs= Interferon Stimulated Genes

44
Q

ISG encoded products include?

A 
Tetherin
TRIM5 alpha
APOBEC3G
OAS= 2'-5' Oligoadenylate synthetase
PKR
IFITM1/2/3
45
Q

What does tetherin do?

A

Binds retroviruses to prevent them escaping the cell and infecting new cells

46
Q

What is OAS?

A

2’-5’- Oligoadenylate synthetase

47
Q

What is PKR?

A

Protein Kinase R

48
Q

IFITM3?

A

Present in the late endosome and can prevent fusion of influenza viruses

49
Q

How does OAS work?

A

Recognises dsRNA
Leads to RNaseL production
All cellular RNA is degraded including host

50
Q

OAS and PKR are both?

A

Interferon induced

51
Q

PKR is induced by?

A

Interferon

52
Q

PKR recognises?

A

dsRNA

53
Q

How does PKR work?

A 
Recognises dsRNA
Autophosphorylation into active PKR
Can phosphorylate eIF2-a
Prevents it from working
Translation is halted
Also leads to NF-kB activation
54
Q

How is cytosolic DNA recognised by?

A

cGAS

55
Q

What is cGAS?

A

Cyclic GMP-AMP synthase

56
Q

cGAS recognition of cytosolic DNA leads to?

A

GTP–> GMP
ATP –> AMP
cGAMP production: cyclic GMP-AMP

57
Q

cGAMP leads to?

A

STING activation

58
Q

STING leads to?

A

TBK1 recruitment

59
Q

What does TBK1 do?

A

Phosphorylates and activates IRF-3

MM- Viruses (13 decks)

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