#20 viral evasion of cellular immune responses Flashcards
(39 cards)
what are the two types of ways that viruses evade immune attack?
1) not being recognised by the immune system
2) interfering with functioning of particular immune mechanisms
what viruses are good at evading the immune response
Large DNA viruses such as poxviruses and Herpesviruses
they can encode a lot of weaponry
how does Herpesviruses evade the immune response?
- it hides latent
EBV hides in b cells
HSV hides in neurons
how do viruses avoid detection by T-cells and Ab’s
antigenic drift and shift
done by influenza and HIV
what are ways of interfering with T-cell priming by DCs?
- blocking TLR signalling to T-cell
- interfere with DC maturation
- interfering with naive t-cell population
how to avoid t-cell recognition
- antigenic variation in t-cell epitopes (influenza and HIV)
- inhibition of processing and presentation of viral peptides
- decreased production of MHC
how to avoid NK cell activation
- mutations in the ligand for the activating receptor
- virus encoded MHC-I like molecules
- upregulation of non-classical MHC molecules
CMV does all of these
how can viruses interfere with cytokines??
- encode virus cytokine homologues
- redirect the t-cell response
- block intracellular cytokine production
- intracellular interference with cytokine function
how can viruses control complement
- produce homologues of complement control proteins
what are the characteristics of a latent infection
virus will infect a non replicating cell OR the viral genome will replicate in conjunction with the host DNA replication so the cell cycle is not disrupted
the viral genome persists in cell
expression of productive cycle viral genes is absent or inefficient
immune detection of the cell with the latent genome is reduced or eliminated
what type of infection is HSV
latent
what type of infection is EBV
latent
what type of infection is Hep. B and C
what do they lead to
chronic - viral persistance
immune exhaustion by producing viral proteins constantly
what type of infection is HPV?
cytopathic but in a inaccessible site - persistance
virus in top layers of skin where there is not a robust immune response
what is an example of a acute infection with very late complications
measles - SSPE
- initial infection with measles
- CNS becomes infected
- the immune system selects for a variant of measles that doesn’t express viral glycoprotein therefore it can no longer bud out of the cell
the genome will spread gradually from neuron to neuron and leads to encephalitis
what viruses use antigenic variation
hiv and influenza
how does antigenic variation allow virus to escape immune system
- allows virus to escape Ab’s
- change in epitopes allow the virus to escape neutralisation by the immune system
occurs spontaneously though the rdrp
how are the ways that viruses can be undetected by T-cells
- drift in t-cell epitopes:
Selective pressure of T cells can lead to escape variants that avoid recognition due to mutations that: - Change the anchor residues of epitope so it no longer binds well to MHC
- Change flanking amino acids so epitope is no longer processed from intact antigen
- Change the epitope in TCR contact residues so it can be processed and presented but existing T cells can no longer recognise the presented peptide
how can HCV escape recognition by t-cells?
In chronic HCV patients, variants have been created with mutations in TCR contact residues - due to these mutations there are no T-cells with TCRs capable of interaction with the anitgens (exploitation of ‘hole in the repertoire’).
how does vaccinia virus inhibit T-cell priming by DCs
- Vaccinia virus and HCV block cytokine induced maturation of DC
- Vaccinia virus encodes a homolog of the cytoplasmic tail of TLR4 that inhibits signal transduction to initiate maturation of the DC (so signalling downstream cannot occur)
How does HIV avoid detection from CD8 cells
- HIV has antigenic variation in CTL epitope
- HIV Nef protein induces the endocytosis of Class I molecule where it gets degraded
- HIV decreases MHC1 gene expression
what does HSV ICP47 do
HSV protein ICP47 binds to cytosolic side of TAP transporter and prevents peptide translocation into the lumen of the ER
avoids detection from CD8
what does CMV protein US6 do
- CMV protein US6 binds to TAP transporter on luminal side and prevents peptide translocation into the cytosol
avoids detection from CD8
what does adenovirus E3 do
- Adenovirus protein E3 binds MHC peptide complex and retains it in ER and inhibits recruitment of TAP to the peptide loading complex
