Viral Immune Evasion Flashcards
What is the ultimate gal of the immune response to a viral infection?
eliminate both the virus and the host cells harbouring or replicating the virus.
Describe how antibody neutralises extracellular virus?
- It blocks viral attachment proteins (e.g., glycoproteins, capsid proteins)
- It destabilises viral structure
What are the five functions of antibody in the anti-viral response?
- neutralise extracellular virus
- Opsonise virus for pathogocytosis
- promotes killing of target cell by the complement cascade and antibody-dependent cellular cytotoxicity.
- resolves lytic viral infections.
- blocks viremic spread to target tissue
Which Ig class is an indicator of recent infection?
IgM
Which Ig class is a more effective anti-viral than IgM?
IgG
Which Ig class is important for pretecting mucosal surfaces?
IgA
What does HIV exist as?
Quasi-species / multiple clades
How does HIV escape antibody recognition?
Exists as multiple quasi-species
How does HBV and Ebola virus evade antibody recognition?
encode secreted surface antigens that mop up antibody, stopping it reaching virus particles or infected cells.
How many serotypes does Dengue Virus exist as?
4 Serotypes
What triggers Dengue Haemorrhagic fever?
Previous infection with one serotype followed by infection with a different serotype can lead to antibody dependent enhancement of disease as virus enters immune cells via antibody and the Fc-Receptor.
Which virus shows antigenic drift?
Influenze virus
What is antigenic drift?
When viruses like flu mutate and evolve each year
Describe how influenza undergoes antigenic shift?
Influenza viruses can also acquire completely new antigens by reassortment with animal viruses
Why is finding a cold vaccine difficult?
Rhinovirus - the most common cold causing pathogen, has too many serotypes
What is the name of the small proteins released by virally infected cells that play a role in immune protection against viruses?
Interferons
How is interferon production induced?
The presence of molecules made by viruses that are sensed by the cell as foreign or in the wrong cellular location
What might trigger the production of interferon from a virally infected cell?
double-stranded RNA
RNA that lacks a 5’ cap
DNA in the cytoplasm.
What does interferon do once secreted from the cell?
Binds to interferon recptors and activates the anti-viral state of the cell and surrounding cells
What does the antiviral state involve?
The Antiviral state involves transcription of hundreds of genes that block viral replication
What is synthesized in the anti-viral state through the transcription of anti-viral genes?
2’5’ oligoadenylate synthetase and protein kinase R.
What are the two type 1 IFNs?
IFN-α and IFN-β
Which cells secrete IFN-β?
All cells
Which cells secrete IFN-α?
Plasmacytoid dendritic cells (PDCs)
Where is the IFN-αR receptor found?
On all tissues
How many genes are there for IFN-β and IFN-α?
There is one gene for IFN-β, but 13/14 isotypes of IFN-α.
What is type 2 IFN?
Type II IFN is IFN-γ
Which cells produce IFN-γ?
Activated T Cells and NK Cells
Which receptor does IFN-γ signal through?
IFN-γR
What is type 3 IFN?
Type III IFN is IFN-λ
What are the main IFN-λ receptors?
IL28R and IL10-β
Where are IL28R and IL10-β found?
On epithelial surfaces
How does Hepatitis B block the production of Interferon?
Through the inhibition of IFN transcription
How does influenza block the production of interferon?
produces a protein (NS1) that counters RNA sensing and prevents polyA processing
How are NK Cells activated?
IFN-α and interleukin-12, which activate macrophages with IFN-γ.
What do NK cells do?
NK cells target and kill virus-infected cells (especially enveloped viruses).
Which types of viruses do NK cells specifically target?
Enveloped viruses
When does an NK cell release toxic substances?
When the NK cell finds a cell displaying fewer than normal MHC molecules
Which viruses might infect a cell and trigger NK cells to release toxic substances?
Cytomegalovirus or Herpes Simplex Virus infected cells
What do macrophages do in the viral response?
filter viral particles from the blood and inactivate opsonised virus particles
What is a function which macrophages and DCs share?
Present antigen to CD4 T cells
What is the viral peptide that Cytotoxic CD8 T cells respond to?
class I MHC protein complexes on the infected cell surface carrying viral proteins
How do viruses like HSV and cytomegalovirus counter the T cell response?
encode proteins that interfere with the MHC antigen processing pathway.
How does HIV evade the immune response?
kills CD4 T cells and alters macrophage function.
How does HSV evade the immune response?
Prevents CD8 T cell killing by encoding proteins which interfere with the MHC antigen processing pathway
