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Virology > Anti-viral Immunity > Flashcards

Anti-viral Immunity Flashcards

1
Q

How do host cells stop viral replication. List at least 5 mechanisms.

A

PRRs: TLR, RLR, NLRs
Transcription Factors: IRFs and NFkB
Restrict viral replication and assembly
Viral Restriction Factors: Tetherin, APOBEC, TRIM5alpha

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2
Q

What PRRs bind to:
ssRNA?
dsRNA?
DNA?

A

TLR7, RIG-I, MDA5
TLR3, RIG-I, MDA5
TLR9, AIM2, NLRs

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3
Q

Define interferon.

A

Cytokines that drive antiviral and anti-tumour responses by interfering with viral replication in host cells. Activate immune cells and upregulate Ag presentation and initiate cell pathways. Promote symptoms like fever during infection.

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4
Q

What are Type I IFNs?
Type II IFNs?
Type III IFNs?

A 
Innate IFNbeta (1st wave) and IFNalpha (2nd wave).
IFNgamma (macrophages/ adaptive T cells)
Innate IFNlambda: IL-29 (first) and IL-28 (2nd)
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5
Q

Describe ISGs.

A

Interferon stimulated genes are stimulated by transcription factors associated with IFN signalling like IRFs and NFkB.

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6
Q

Describe first wave IFN signaling.

A

Mediated by PRRs. Initiates anti-viral response INSIDE host cell. Produces IFNs, and ISGs.

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7
Q

Describe second wave IFN signalling.

A

Is a positive amplification loop which propagates anti-viral responses through cells of infected tissue. Autocrine/paracrine effects. Produces more IFNs and ISGs.

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8
Q

Define viral restriction factors.

A

Proteins and enzymes that limit virus replication in hosts. There are multiple mechanisms and strategies directly for replication. Part of host cell’s intrinsic anti-viral immunity measures.

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9
Q

How are restriction factors express and induced?

A

They are expressed at basal levels an induced by IFN signalling cascades which can be amplified.

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10
Q

What is Trex1?

A

A viral restriction factor that degrades cytoplasmic DNA.

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11
Q

Do humans have Trex1? What does it do?

A

Humans have a mutant version that mounts chronic anti-viral responses in the presence of ERV DNA.

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12
Q

What is essential for limiting retroviral replication?

A

Innate immune signalling

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13
Q

Induction of host restriction factors with RT viruses is dependent on what?

A

IFN response

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14
Q

What kind of protease does HIV have?

A

Aspartic protease

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15
Q

What happens in HIV positive people when given HIV protease inhibitors?

A

Caused decline in opportunistic infections.

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16
Q

What does the HIV protease have an effect on?

A

RIG-I signalling pathway.

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17
Q

How can a virus evade IRF3

A

Inhibit phosphorylation, dimerization, or nuclear translocation
Degrate/Sequester IRF3
Inhibit interaction with transcriptional co-activators of target genes

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18
Q

What does the Ebola protein VP35 do? How does this work?

A

Inhibits phosphorylation of IRF3 which prevents dimerization and nuclear translocation

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19
Q

Name some viruses which can inhibit IRF3 activation.

A

Ebola, SARS coronavirus, PLpro, Dengue, etc.

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20
Q

What is SFTS virus? How is SFTS virus transmitted?

A

SFTS bunyavirus is an emerging pathogen. By ticks

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21
Q

What does SFTS cause in humans?

A

high fever, loss of WBCs and platelets, possibly multiorgan failure

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22
Q

How does SFTS virus evade the immune system? What other viruses do this?

A

It sequesters the IRF3.

RSV NS, Porcine epidemic diarrhea virus NS, HSV ICPO, Arenavirus NP, etc.

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23
Q

How does Rotavirus NSP1 evade the immune system? What other viruses do this?

A

Degrades IRF3 via the proteosome.

HTLV-1 via SOCS1, and BoHV ICPO

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24
Q

What viruses inhibit the transcriptional activity of host IRF3?

A

HHV8, EBV, vaccinia etc.

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25
Q

What is PKR? What does PKR do?

A

Protein kinase RNA-activated.
Recognizes dsRNA in the cytoplasm, shuts of protein synthesis (by phosphorylating eiF2alpha), and activates NFkB (by degradation of IkBbeta).

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26
Q

How can viruses evade PKR?

A

Decoy dsRNA, PKR degradation, hiding virus dsRNA, blocking PKR dimerization, PKR dephosphorylation

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27
Q

Name some viruses able to block PKR.

A 
Influenza A (via non structural 1A protein)
Adenovirus
EBV (via EBER)
HIV (via TAR and Tat)
Poliovirus (via 2A pro)
Vaccinia
Reovirus
HCV
HSV
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28
Q

Which cells are crucial in limiting HTLV-1 replication? How?

A

Stromal cells (epithelial and fibroblast in particular) via secretion of type I IFNs

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29
Q

What does HTLV-1 infect?

A

Primary pDCs.

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30
Q

What is the Tax protein? What is its function?

What protein does the opposite and where does it come from?

A

Tax is a protein in HTLV-1 which promotes NFkB signalling while impairing IRF3 signalling.
HBZ inhibits NFkB p65 DNA binding and promotes degradation while also inhibiting IRF signalling. Also HTLV-1?

31
Q

What does SOCS1 do in the cell?

What does it do with HTLV-1 present?

A

It affects multiple different pathways!

It degrades IRF3 and does not allow it to enter the nucleus.

32
Q

HTLV-1, like HIV, is associated with several ___ ___

A

Opportunistic infections

33
Q

Describe the innate immune system.

A

Rapid, intense, redundant, limited and fixed specificity to intact antigen, no memory.

34
Q

Describe the adaptive immune system.

A

Requires time, requires Ag presentation, Dependent on T cells, Specific to intact and processed antigen, memory responses.

35
Q

Describe how B cells recognize pathogens.

A

B cells use BcRs also called Immunoglobulin (Ig) which detect macromolecules like proteins, lipids, polysaccharides, and chemicals.

36
Q

Describe how T cells recognize pathogens

A

T cells use TcRs which recognize/detect MHC-peptide complexes.

37
Q

Describe how antigen presenting cells recognize pathogens.

A

APCs recognize peptides via MHC molecules

38
Q

How is endogenous Ag recognized? By what? To whom?

How is exogenous Ag recognized? By what? To whom?

A

MHC I - peptide presentation to CD8+ T cells

MHC II - peptide presentation to CD4+ T cells

39
Q

Name the APCs

A

DCs, macrophages, monocytes, B cells, epithelial cells, and eosinophils.

40
Q

How are T cells positively selected?

How are T cells negatively selected?

A

Weak recognition of the MHC.

Responding to self.

41
Q

What is the TcR-CD3 complex?

A

A way for the T cell to recognize the MHC complex. TcR and CD3 are next to each other on the T cell and both need to be activated in order to react

42
Q 
Name the T cell counterpart to the DC sample. Describe whether it is activating or deactivating if applicable.
MHC II
MHC I
CD80/CD86
CD40
A

MHC II - TCR+CD4
MHC I - TCR+CD8
CD80/86 w - CD28 (activating) / CTLA4 (deactivating)
CD40 w CD40L activating

43
Q

Describe how DCs initiate T cell tolerance.

A

A resting DC presents low Ag and no costimulation with short contacts.

44
Q

Describe how DCs initiate T cell effectors.

A

An active DC presents high Ag, high costimulation with cytokines present, with long contacts.

45
Q

Describe how DCs initiate T cell memory.

A

An exhausted DC presents high Ag, high costimulation with short contacts.

46
Q

DC instruction of T cells determines which three things in the T cell?

A

On/Off
flavour or T cell
Population size of T cells

47
Q

Define cytokine

A

Low MW protein which regs type, intensity, and duration of immune response

48
Q

Define chemokine

A

cytokine which mediates chemotaxis

49
Q

DCs secrete which IL at rest?
Which ILs do DCs secrete to effect Th1 cells?
Which ILs do DCs secrete to effect Th2 cells?

A

IL6
HIGH IL12 and 18
LOW IL 12 and 18

50
Q

Can Th1 cells affect Th2 cells? If so, how?

A

Th1 –> Th2 = IFNgamma

Th2–> Th2 = IL4/IL10

51
Q

What are the functions of Th1 cells?

A

Killing microbes/infected cells and reacting with B cells

52
Q

What are the functions of Th2 cells?

A

Responding to allergy, affecting mast cells, interacting with B cells

53
Q

What are the four kinds of T cell subsets?

Describe further subsets or functions of these.

A

CD4+ helpers: Th1, Th2, Th17, Tregs
Tregs: FoxP3 and IL10 secreting
CD8+ cytotoxic: antiviral and anti-tumour
NKT: inflammatory, antiviral, and anti-tumour

54
Q

How can a virus avoid detection by T cells?

A 
Block MHC activity by...
Block host proteosome activity
Block Tap import of peptides into ER
Block MHC maturation/peptide loading
Prevent MHC presentation on APCs
55
Q

How does EBV evade T cell response?

A

EBV uses protein EBNA1 to block proteasomal breakdown of peptides so they can’t be presented by MHC.

56
Q

What is a virokine?

A

Virus encoded secreted proteins which mimics host cytokines. Usually in DNA viruses

57
Q

What kinds of virokines are there? I.e. what do they mimic?

A

Cytokines, receptor/binding homologues, viral growth factors, and SERPINs

58
Q

How can viruses alter cytokine signalling?

A

By mimicking host proteins.

59
Q

Name a chemokine that is mimicked. Name the virus that does this and how.

A

vIL10 mimicks IL10 by EBV using BCRF1

60
Q

What is Castleman’s disease? What is the presentation of symptoms for Castleman’s? How is it treated?

A

Disfunctional cytokine networks by HHV8 encoding vIL-6. This causes lymphoproliferative diseases.
Spotty bright red patches near lymph nodes.
Cured by anti-IL6 treatment.

61
Q

Which polymerases have the highest mutation rate?

A

RdRp and RdDp because they are encoded by viruses and have no proof reading.

62
Q

What is a viral quasi-species?

A

Viral genomes with point mutations in genes which leads to distinct viruses.

63
Q

When can virus specific CTLs not recognize virus infected cells?

A

if the mutations in the genome occurred in the epitope of the amino acid sequence.

64
Q

What is an escape mutant?

A

A virus who has had a point mutation in the epitope portion of the AA sequence of its genome causing it to be unable to be recognized by the CTLs.

65
Q

Why are escape mutants important?

A

They allow viruses to stay one step ahead of the immune system response.

66
Q

When can viral epitopes undergo mutations?

A

All the time unless in highly conserved region that is necessary for protein function

67
Q

Escape mutants can cause a loss in viral fitness. How can they fix this?

A

Compensatory mutation.

68
Q

Name a virus in which escape mutants are very common. Describe this.

A

HIV-1
The virus has much selective pressure through out the body and slightly different variants of the virus can be found in many areas.

69
Q

What is the function of the protein p53?

A

p53 is an anti-oncoprotein that induces apoptosis when activated. It can kill virally infected cells before viruses can reproduce.

70
Q

Name a way for a virus to trigger p53

A

SV40 and HPV activate phosphorylation which causes apoptosis.

71
Q

Which viruses encode Bcl-2 family proteins. What do Bcl-2 proteins do?

A

Large DNA viruses, All gamma herpes, and adenoviruses. Bcl-2 blocks apoptosis (p53)

72
Q

Name a virus associated with cancer. Describe which cancer it causes, which protein is uses, and the mechanism.

A

HTLV-1 caues Adult T cell leukemia via the Tax protein. It is involved in the regulation of the cell cycle, apoptosis, cell transcription, NFkB, etc.

73
Q

What does NFkB dependent lack of apoptosis result in?

A

Uncontrolled proliferation and cell transformation to cancer.

Virology (17 decks)

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