Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Infection and Immunity > Innate immunity against viruses and viral evasion strategies > Flashcards

Innate immunity against viruses and viral evasion strategies Flashcards

1
Q

What are the components to innate antiviral immunity?

A

Barriers at sites of microbe entry
Intrinsic defences
Phagocytosis
Complement
Inflammatory response
Cytokines and interferon
NK cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the sites of microbe entry?

A

Conjuctiva
Respiratory tract
Alimentary tract
Urogenital tract
Anus
Skin
Arthropod
Capillary
Scratch/injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the physical barriers?

A

Skin
Mucosal surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the chemical barriers?

A

pH
Secreted factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are sentinel cells?

A

Any cell that has a prominent role in host defence
e.g. macrophages, DCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the intrinsic defences?

A

Apoptosis
Restriction facotrs/intrinsic immunity
Epigenetic silencing
RNA silencing
Autophagy/Xenophagy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why is apoptosis bad for the virus?

A

It prevents completion of the life cycle and triggers surface signals for clearance by macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does adenovirus evade apoptosis?

A

E1B-19K protein expressed by adenovirus counteracts E1A-induced intrinsic apoptosis
It is a viral BCL-2 homologue
Prevents oligomerisation of BAX and BAD, preventing mitochondrial pore formation and no cytochrome c, Smac release
XIAP will therefore inhibit apoptosis by binding to effector caspases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does Kaposi’s sarcoma-associated herpesvirus (HHV-8) evade apoptosis?

A

Viral Bcl-2 homologue inhibits mitochondrial pore formation by binding BAK
vFLIP protein blocks interaction of death receptor-adaptor complex with cellular effector FLICE (procaspase-8), which prevents initiation of caspase cascade
vIAP protein binds to apoptosome and prevents activation of effector caspases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are restriction factors?

A

Host cellular proteins that act as a frontline defence against viral infections
They recognise and interfere with stages of the replication cycle of viruses and therefore block infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name some restriction factors

A

APOBEC3G
TRIM5a
Tetherin
SAMHD1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe APOBEC3G

A

A highly potent ssDNA cytidine deaminase
Associates with nascent HIV nucelocapsids and is incorporated into new virions
When these virions infect other cells and the viral transcription complex is formed, APOBEC3G deaminates cytidine to uridine, forming hypermutated defective proviruses or are degraded so cannot cause infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe TRIM5a

A

Targets incoming capsids to proteasomes
Very species-specific
Block retroviral infections by binding viral capsids and preventing reverse transcription
Prevent uncoating of virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does tetherin work?

A

Blocks budding by enveloped viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe SAMHD1

A

A phosphohydrolase that converts dNTPs to inorganic phosphate and depletes the pool of dNTPs available to reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does HIV evade restriction factors?

A

Vpu protein removes tetherin from the cell surface
Vif impairs translation and intacellular stability of APOBEC3G
Vpx protein counteracts SAMHD1 to allow reverse transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is epigenetic silencing?

A

A nuclear event where foreign DNA molecules that enter the cell are quickly organised into transcriptionally silent chromatin
Involves PML bodies
Silences DNA viruses e.g. adenoviruses and herpesviruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What do large DNA viruses encode?

A

Proteins that prevent deposition of inhibitory histones and other chromatin compounds onto viral DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe phagocytosis as a component of innate viral immunity

A

Carried out in vertebrates by DCs, macrophages and neutrophils
Clears pathogens but also presents peptides on MHCs - this promotes development of reactivation of the adaptive immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do phagocytes see viruses?

A

Macrophages have phagocytic receptors that bind microbes and their components
e.g. mannose receptor, complement receptor, lipid receptor, dectin-1, scavenger receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does complement bind to some viruses in an antibody-dependent manner?

A

Classical pathway via direct binding of C1q to the envelope glycoproteins of some viruses
Lectin pathway via binding of MBL to viral surface carbohydrates
Alternative pathway on enveloped viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How do viruses evade complement?

A

Complement control proteins incorporated into envelope
Can be passive or active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Give examples of active evasion of complement

A

Vaccinia C3L gene product VCP is a complement control protein that binds to and inactivates C3b and C4b
Vaccinia B5R product recruits host complement control proteins into the envelope
KSHV-encoded KCP is incorporated into the virion and enhances the decay of classical C3 convertase and induces the degradation of activated complement factors C4b and C3b by a serine proteinase factor I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is pinocytosis?

A

Cell ‘drinking’ - ingestion of liquid into a cell by budding of small vesicles from the cell membrane
Anything taken up by cells in pinocytosis is cleared by proteolysis and presented on the surface through MHC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Why does pinocytosis occur?

A

For immune cells such as DCs, macrophages and neutrophils to sample their environment

26
Q

What are the 2 distinct roles of macrophages in innate immunity?

A

Phagocytosis - material is destroyed in lysosomes
Activated macrophages produce cytokines and chemokines to stimulate both innate and adaptive immune responses - triggers the inflammatory response and can promote local anti-viral state

27
Q

What is the inflammatory response?

A

A generic defence mechanism whose purpose is to localise and eliminate injurious agents and to remove damaged tissue components

28
Q

What does the inflammatory response lead to?

A

Enhanced permeability and extravasation
Neutrophil recruitment
Enhanced cell adhesion
Enhanced clotting

29
Q

What 2 signals are needed for activation of the inflammatory response?

A

Stimulation of transcription of pro-inflammatory cytokines and chemokines
Activation of ICE/caspase-1 which cleaves the inactive precursor forms of IL-1B and IL-18 (the inflammasome)

30
Q

What activated the inflammasome?

A

Viral PAMPs sensed by PRRs

31
Q

Name some anti-viral PRRs

A

TLR3, 7, 8 and 9
RIG-I
MDA5
DAI
RNApol-III
Ku70/80
AIM2
IFI-16

32
Q

Where are TLR7, 8 and 9 expressed?

A

In plasmacytoid DCs and macrophages

33
Q

Where is TLR3 expressed?

A

Expressed widely but shows elevated levels on myeloid DCs, macrophages, endothelial and epithelial cells

34
Q

Where are RIG-I and MDA5 expressed?

A

Ubiquitous

35
Q

Where are DAI, RNApol-III and Ku70/80 expressed?

A

Ubiquitous

36
Q

Where is AIM2 expressed?

A

In macrophages

37
Q

Where is IFI-16 expressed?

A

In macrophages

38
Q

Why is an overactive inflammatory response bad for resolving influenza infections?

A

High pathogenicity strains can trigger cytokine storms that lead to severe lung damage

39
Q

How is an overactive inflammatory response treated?

A

IL-1 antagonists and other anti-inflammatory drugs

40
Q

How is inflammation evaded by viruses?

A

General block to inflammatory cytokine production
Direct inhibition of caspase-1
Synthesis of scavenger receptors
Blocking of inflammasome assembly
NS1 inhibits RIG-I inflammasome

41
Q

What do viruses trigger?

A

Production of anti-viral cytokines

42
Q

What induces interferons?

A

Viral infection

43
Q

What do interferons offer?

A

Cross-protection

44
Q

What are the types of interferon?

A

Alpha
Beta
Epsilon
Kappa
Lambda-1, 2 and 3
Gamma

45
Q

What do the IFN lambdas do?

A

Protect epithelial surfaces

46
Q

What do IFN alpha and beta do?

A

Protect all other tissues

47
Q

What is the antiviral state?

A

The result of a signalling pathway induced by IFN-a or IFN-b following viral infection
Limits replication in infected cells and viral spreading in non-infected cells by

48
Q

Describe IFN and the antiviral state

A

IFN-a/b binds to receptor and triggers signal transduction pathway (JAK/STAT pathway)
This turns on 1500 genes

49
Q

What does it mean when a virus cannot block the IF system?

A

It is severely attenuated

50
Q

Give examples of severely attenuated viruses

A

Influenza NS1 stains are severely attenuated and can be used as the basis of vaccine strains
BVDV Npro strain is severely attenuated and can be used as a vaccine strain
PIV5VC is severely attenuated and can be used as an experimental vaccine

51
Q

How is the IFB-b promoter activated?

A

Virus PAMPs bind PRRs
Activates transcription factors NF-kB and IRF-3 in the nucleus
IRF-3 activates PRD I/III on IFN-b promoter
NF-kB activates PRD II on IFN-b promoter

52
Q

What viruses inhibit activation of IFN-b promoter?

A

Paramyxovirus V and Influenza NS1 block PRRs, preventing recognition of PAMPs so no activation of NF-kB and IRF-3
BVDV Npro inhibits IRF-3 so no activation of PRD I/III

53
Q

Describe how type 1 interferons signal

A

Through heterodimeric transmembrane receptor comprising subunits IFNAR1 and IFNAR2
Engagement of type 1 IFNs with the receptor causes dimerisation of the 2 subunits and autophosphorylation of JAK1 and Tyk2
These phosphorylate the intracellular domains of the receptors to establish docking sites for STAT1 and STAT2
STAT1 and 2 are subsequently phosphorylated by the JAKs
Phosphorylated STAT1 and STAT2 form a heterodimer that binds IFN regulatory factor IRF9 in the cytoplasm, forming heterotrimeric transcriptional factor complex IFN-stimulated gene factor 3 (ISGF3)
ISGF3 translocated to the nucleus and binds cis element IFN-stimulated response element (ISRE)
This drives the transcription of hundreds of ISGs that are involved in the antiviral state

54
Q

How do poxviruses inhibit the JAK/STAT pathway?

A

Produce secreted IFN-receptor-like decoy factors for IFNs to bind to instead of the actual heterodimeric transmembrane receptor

55
Q

How does herpes simplex virus 1 inhibit JAK STAT?

A

Induces secretion of an IFN type 1 antagonising protein

56
Q

How does measles virus suppress JAK STAT?

A

Suppresses IFN-a induced viral state but not IFN-g induced signalling
Measles virus accessory proteins C and V form a complex with the IFNAR1 chain

57
Q

How do influenza A viruses disrupt the JAK STAT pathway?

A

By reducing expression of the IFN receptor
NS1 protein produced by influenza A viruses reduced IFN production and inhibits IFN signalling
NS1 targets both chains of the IFNAR receptor by reducing their expression at the transcriptional level

58
Q

How does EBV affect IFN signalling?

A

Encodes the protein BZLF1 that decreases ability of IFN-g to activate several genes in the pathway
Inhibits phosphorylation of STAT1
Decreases expression of IFN-g receptor

59
Q

Why are NK cells important in DNA virus infections?

A

NK cells secrete IFN-g to act against viruses and allow lysis of virally infected cells

60
Q

How does CMV inhibit NK cell function?

A

Produces UL40 and UL142 proteins that act as decoy NK cell receptors
Produces UL16 proteins that downregulate NK activating receptors

Infection and Immunity (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions