Pathogens (Jeremy Lecture 3) Flashcards

1
Q

Describe the characteristics of the innate immune response to a virus

A

1) Does not require previous viral exposure
2) Activated and responds in minutes to hours following infection
3) Involves pattern-recognition receptors and other innate signalling pathways

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2
Q

What components produce the antiviral state and how does this occur?

A
  • Interferons
  • Produced by innate immune activation
  • Secreted interferons (INF) bind to INF receptors on uninfected cells
  • Binding causes synthesis from over 1000 genes (ISG: INF stimulated genes)
  • Interferons induce the cellular antiviral state
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3
Q

How do viruses inhibit interferon activation and function?

A

1) Prevention of signalling pathway activation (blocking interferon activation)
- dsRNA binding proteins, such as influenza virus NS1
2) Inhibition of signalling pathway
- PKR inhibitors
- STAT inhibitors

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4
Q

What are the main products of the innate immune system that cause inflammation?

A

Cytokines

- TNF-alpha in main early stage cytokine causing inflammation

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5
Q

What do cytokines cause?

A
  • Increased blood flow (vasodilation)
  • Increased blood vessel permeability (endothelial cell tight junctions)
  • Influx of immune cells from blood to tissue
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6
Q

What are the main disease symptoms caused by inflammation?

A
  • Redness
  • Pain
  • Heat
  • Swelling
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7
Q

Why do viruses inhibit the inflammatory response?

A

Inflammation inhibits viral replication and infection

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8
Q

What is the name for viruses that do not cause an inflammatory response?

A

Non-cytopathic viruses

- Harder to cure

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9
Q

Describe the characteristics of the adaptive immune response in relation to viral infection?

A
  • Activated days after initial infection
  • Activated by innate immune system
  • Cell mediated and humoral immunity
  • Memory response
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10
Q

What are the effectors of cell mediated immunity and what does each do?

A

IFN-gamma secreted by Th and CTLs induces antiviral state
Cytotoxic T cells destroy virus infected cells
NK cells and macrophages destroy virus infected cells too

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11
Q

What are the effectors of humoral immunity and what does each do?

A

Primary secondary IgA - inhibits virion attachment

Primary IgG - inhibits fusion of enveloped viruses to PM

IgG and IgM antibodies - Opsonisation and complement activation

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12
Q

What is immunopathology?

A

Immune response to a disease

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13
Q

Name some viruses associated with CD8+, CD4+ and B-cell mediated immunopathology

A

CD8+:

  • HIV-1
  • Hepititis B

CD4+:
Measles
Herpes simplex

B-cell mediated:
Dengue virus

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14
Q

Name the different responses in viral-induced immunopathology

A
  • Innate immunity killing
  • Inflammation
  • CD4+ cell mediated
  • CD8+ cell mediated
  • B cell mediated
  • Molecular mimicry/autoimmunity
  • Immunosuppression
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15
Q

How and what free radicals are produced during the inflammatory response?

A
  • Nitric oxide (NO) is produced by nitric oxide synthase, a IFN-inducible enzyme
  • Superoxide (O2-) is also produced
  • Low NO is protective, high NO causes tissue damage
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16
Q

What is autoimmunity?

A

Host immune response directed against its own tissue

17
Q

By what 2 main mechanisms can viruses cause autoimmunity?

A

1) Directly trigger autoimmunity
- cytolysis can lead to release of cellular antigens and then autoimmunity

2) Molecular mimicry
Viruses can mimic components of the hosts immune system

18
Q

How can viruses cause molecular mimicry?

A
  • Some viral and host proteins share sequence homology and may have similar antigenic regions
19
Q

Name some epitopes that are shared between specific viruses and the host

A

Poliovirus VP2
Acetylcholine receptor

HIV p24
IgG contant regions

Papilloma virus E2
Insulin receptor

20
Q

Name some ways in which viruses change the immune system to benefit themselves

A
  • Evasion (latency, antigenic variation, blocking innate recognition
  • Inhibition of innate pathways
  • Inhibition of complement
  • Immune cell killing
  • Modulation of apoptosis/autophagy
  • Blockage of apadtive immunity
21
Q

What does interferon signal to the nucleus and what does it cause?

A
  • IFN-alpha binds to the IFN alpha/beta receptor (IFNAR) and causes intracellular JAK/STAT signalling
  • Requires the dimerisation of STAT1 with STAT2
  • IFN-gamma binds to IFNGR
  • Causes JAK/STAT signalling via STAT1 dimerisation with STAT1
  • STAT signalling activates ISGs (INF stimulated genes): over 1000 genes
  • Induces an anti viral state
22
Q

How does influenza virus inhibit INF JAK/STAT signalling?

A

Influenza protein NS1 blocks STAT phosphorylation and activation thus preventing STAT signallinh

23
Q

How can Influenza induce INF activation?

A
  • Temporary intermediate dsRNA activates Protein Kinase R (PKR)
  • PKR activates INF
24
Q

What does influenza do to prevents PKR mediated INF activation?

A

NS1 protein binds dsRNA and prevents it from activating PKR

25
Q

How does Ebola induce large scale inflammation that leads to serious disease?

A
  • Ebola virus infects macrophages, resulting in large scale production of cytokines (cytokine storm) that increase vascular leakage
  • Production of some cytokines i.e IL-10 associated with fatal disease
  • Cytokines also signal for the recruitment of other inflammatory cells
26
Q

What is Apobec? What does it do?

A
  • An anti-viral RNA editing protein
  • It is produced from an INF stimulated gene
  • Deaminated C to U in the RNA genome of viruses - kills the virus
  • Blocks HIV replication
27
Q

How does HIV evade killing via Apobec?

A

Encodes Vif which binds to Apobec and targets it to the proteasome

28
Q

In what 2 ways does HIV use Nef to evade the adaptive immune system?

A

1) Nef binds to MHC class I in the trans-Golgi network
- Traffics MHC to the lysosome instead of the PM
- MHC degraded by lysosomal enzymes
- Cell not recognized as infected

2) Nef binds CD4 on the plasma membrane
- Also traffics CD4 to the lysosome

29
Q

Name another 2 ways that HIV can evade the immune system

A

1) Changing its antigens
- HIV RNA genome replicates and induces copying errors
- Changes in antigenic regions on the cell surface - harder to retain memory to HIV infection

2) Dormant CD4+ T cells
- Some CD4+ cells become memory CD4+ cells and are therefore dormant
- Not expressing antigens and not replicating
- HIV can become latent in these cells and survive