Immune Evasion by Viruses Flashcards
Whats the role of an antibody in regard to a virus?
- Antibody neutralises extracellular virus- blocks viral attachment proteins and destabilises viral structure
- Antibody opsonises virus for phagocytosis
- Antibody promotes killing of target cell by compliment cascade and antibody-dependent cellular cytotoxicity
- Antibody resolves lytic viral infections
- Antibody blocks viremic spread to target tissue
Whats the role of IgG and IgM in viral infections?
IgM is an indicator of recent or current infections
IgG is more effective antiviral than IgM
How does human rhinovirus evade antibody recognition?
Human rhinovirus exists as hundreds of allergenically distinct serotypes
How does HIV evade antibody recognition?
HIV exists as multiple clades or quasi-species
How does Hep B and Ebola evade antibody recognition?
Hep B and Ebola virus encode secreted surface antigens that mop up antibody, stopping it from reaching infected cells
How does Dengue virus evade antibody recognition?
Dengue virus exists as 4 serotypes.
Previous infection of 1 serotype then reinfection with a different serotype can lead to antibody dependent enhancement of disease as virus enters immune cell via Fc receptor.
This triggers Dengue Haemorrhagic Fever
How does Influenza virus evade antibody recognition?
Influenza virus mutate and evolve to change year on year- antigenic drift
Influenza can also acquire completely new antigens by reassortment with animal viruses. This is antigen drift and can lead to pandemics
What consequences does viral immune evasion have on vaccination?
Too many rhinovirus serotypes makes finding a cold vaccine very difficult
New influenza virus vaccine is required each year to reflect circulating virus types
What are interferons?
Virally infected cells produce and release small proteins called interferons which play a role in immune protection against viruses
Interferon is induced by molecules made by viruses that are sensed by the cell as foreign or in the wrong cellular location e.g:
- double stranded DNA
- RNA that lacks 5’ cap
- DNA in cytoplasm
What occurs after IFN is secreted?
Interferon is secreted by virally infected cells and binds to interferon receptors
IFN initiates the antiviral state in infected cells and surrounding cells
IFN activates NK cells and systemic antiviral response (Activates MHC I)
What is the antiviral state?
Involves transcription of hundreds of genes that block viral replication e.g. 2’5’ oligoadenylate synthesise and protein kinase R
What are the 3 types of interferon?
Type I- IFN alpha and IFN beta
Type II- IFN gamma
Type III- IFN Lambda
What is type I IFN?
IFN alpha and beta
IFN beta secreted by all cells and IFN-alpha-R receptor is present on all tissues (receptor is for both IFN a and B)
Plasmacytoid DCs (PDCs) are specialised IFN- alpha secreting cells
Theres one gene for IFN beta but 13/14 isotopes of IFN alpha
What is type II IFN?
IFN gamma
Produced by activated T cells and NK cells
Signals through IFN-gamma-R
What is type III IFN?
IFN lambda
Signals through receptors IL28R and IL10-beta also known as IFN-lambda receptors
Receptors mainly present on epithelial surfaces
How do some viruses evade IFN?
Viruses like Hep B and Influenza block production of IFN transcription (HBV) or influenza produces NS1 protein that counters RNA sensing and prevents polyA processing
What are NK cells?
NK cells are activated by IFN- alpha and IL-12 which activate macrophages with IFN- gamma
NK cells target and kill virus infected cells
How does NK cell kill virally infected cell?
When NK cell finds a cell displaying fewer than normal MHC molecules it releases toxic substances which kill virally infected cell
What is the role of macrophages?
Macrophages filter virus particles from blood
The inactivate opsonised virus particles
What is the role off dendritic cells?
Immature and plasmacytoid DCs produce IFN-alpha and other cytokines
DCs initiate and determine the nature of CD4 and CD8 T cell response
DCs and macrophages present antigen to CD4 T cells
What is a T cells role in viral infections?
T cells control enveloped and noncytolytic viral infections
T cells recognise viral peptides presented by MHC molecules on surface
Antigenic viral peptides can come from any viral protein
What do CD4 and CD8 cells do in response to viral infection?
CD8 cells respond to viral peptide: MHC I protein complexes on infected cell surface
CD4 Th2 responses may be detrimental if they prematurely limit the Th1 response
How do viruses that result in chronic infections differ?
They have ways to counter T cell response
Many DNA viruses such as HSV and CMV encode proteins that interfere with MHC antigen processing pathway
How do viruses impair lymphocyte function ?
HIV cells kill CD4 cells and alter macrophage function
HSV can prevent CD8 T cell killing
