Viral Evasion of Host Community Flashcards
- Cellular immunity clears viral infection via X but is YY
T cells (CD8) but is short lived
- Humoral immunity is X with Y
is B cells with antibodies
- Internal viral proteins can be targets of cellular immunity-> They tend to XX than surface antigens
vary less
- Cells cut up pieces of viral and cellular peptides in the X
proteosome
viral and cellular peptides are loaded onto XXX for recognition via T cells
MHC class I
How are viral proteins presented on the surface? ( goes to X, then loaded on to W, then goes to Y then goes to Z)
- These peptides are transported through the ER and get loaded into an MHC class I molecule
- This is transported to Golgi and then the cell surface
What is the co stimulator for a T cell
CD8
What transports viral peptides to the ER
TAP
What is the purpose of tap
transports viral peptides to the ER
3 viruses that avoid antigen presentation onto cell surface (in a way that takes place before Tapasin)?
- EBV
- HSV
- CMV
How does EBV avoid antigen presentation on cell surface?
EBNA1 cannot be processed by the proteasome
How does HSV avoid antigen presentation on cell surface?
- HSV ICP47 blocks access of the processed peptide to TAP on the ER
How does CMV avoid antigen presentation on cell surface? (2)
- CMV US6 prevents peptide travelling through TAP by blocking other side and stopping ATP binding and so has the same effect as HSV
- CMV US3 protein binds tapasin and prevent peptides being loaded to MHC
Which virus prevents peptide travelling through TAP by blocking other side and stopping ATP binding and so has the same effect as HSV
CMV
Which virus blocks access of the processed peptide to TAP on the ER
HSV
Which virus blocks access of the processed peptide to TAP on the ER
EBV
What molecule places peptide fragments on to MHC class I for presentation on the cell surface
Tapasin
What does tapasin do
places peptide fragments on to MHC class I for presentation on the cell surface
Which 2 viruses avoid antigen loading onto MHC via tapasin?
CMV
Adenovirus
How does CMV interfere with tapasin?
- CMV US3 protein binds tapasin and prevent peptides being loaded to MHC
How does adenovirus interfere with tapasin? (2)
- Adenovirus E3-19K protein prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum
Which virus has a protein that binds tapasin and prevent peptides being loaded to MHC
CMV
Which virus has a protein that prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum
Adenovirus
which virus interferes with antigen presentation at the cell surface?
KSHV
How does KSHV interfere with antigen presentation at the cell surface?
kK3 protein induces polyubiquitinylation and internalization of MHC (it gets dragged back in from the cell surface) From the internalized endosome, MHC is passed to lysosomes where it is degraded
Which virus induces polyubiquitinylation and internalization of MHC (it gets dragged back in from the cell surface) From the internalized endosome, MHC is passed to lysosomes where it is degraded?
KSHV
Why is HPV an effective virus even with a short genome?
- This short genome is feasible because the proteins they code for have multiple purposes.
What do the virulence factors of HPV cause? (3)
- E6 and E7 stop the IFNA signaling pathway, as well as the cGAS pathway
- E5 then stops the presentation of its peptides on MHC by holding on to it
How does CMV avoid missing-self being displayed on the cell surface
viruses encode MHC analogues (CMV gpUL40)
2 ways viruses can evade the missing self mechanism?
viruses encode MHC analogues (CMV gpUL40) or upregulate MHC
What cells detect missing self MHC molecules
NK cells
What is antigenic variation?
Continued rapid evolution driven by antigenic pressure from host
influenza antigenic shift is caused by…
- Introduction of new subtypes from animal source
what is the major spike protein/viral antigen in flu
Haemogglutinin
Which part of haemogglutinin/any viral antigen is variable and which is fairly constant
Globular head domain (bit where antibodies bind and where receptors bind) is highly variable and the stalk is fairly constant
Why is the stalk of a viral antigen fairly constant? (2)
Constant stalk may be because the structure is extremely important and viruses that have a mutation in the stalk probs just die, or because none of our antibodies really target that bit so there has been no evolutionary drive for that bit to change
Target for a universal flu vaccine?
Constant stalk of the haemogglutinin
What on antigenic cartography tells us how different the viruses are from each other
Distance between the dots
How can we skew Ab response towards the HA stalk? (5)
Headless HA
Hyperglycosylating the antigen binding head
Peptides against fusion peptide and ectodomain
Ferritin based nanoparticles displaying HA
Sequential immunisation with chimeric HA
Explain Ferritin based nanoparticles displaying HA
Ferritin nanoparticle core - This makes the HA’s a lot more separated than on the normal flu particle, giving access to the core easier.
Explain Sequential immunisation with chimeric HA
When administering vaccine boosts, change the head but keep the stalk, rather than do the usual of giving the exact same antigen each time and gradually the immune system will adapt to fight what it sees the most often
How does the HIV spike GP120 evade neutralisation? (4)
- Large space between spikes prevents Ab crosslinking meaning efficiency of antibody binding is reduced
- Extensive glycosylation masks antibody epitopes
- Functionally important parts of the molecule are poorly accessible, CD4 binding site, redundant amino acids are visible to B cell receptor and antibodies
- Huge variation in the redundant amino acids means most antibodies are highly clade specific
What are broadly neutralising Abs in HIV therapy
Antibodies that can cross-react with HIV strains exist alongside the virus in people who control the infection
why is it difficult to make a vaccine for rhinovirus
Big antigenic variation
- Human rhinoviruses cause the common cold
- They exist as more than 120 antigenically distinct serotypes that co-circulate
- Impossible to make a vaccine against them all
What does a vaccine against all three poliovirus’ at once result in
in virus interference (where one of the 3 serotypes survived better in people than the others and cause problems) and poor response to one component
How is a dengue infection detected (2)
- Detected by increase in red cell count and decrease in protein level in blood
Treatment for dengue?
- Treat with iv fluid replacement
What is antibody dependent enhancement of dengue
- Antibody generated against a previous infection can bind but not neutralize, and lead to ADE (ANTIBODY DEPENDENT ENHANCEMENT), causing Dengue Haemorrhagic Fever Basically, antibodies for one serotype of the virus actually end up helping the other serotypes to gain entry into cells, leads to cytokine storm
why is measles vaccinations especially important (not just bc it prevents measles)
Measles vaccine helps maintain immunological memory and so protects against more than just measles
introduction of measles vaccine was associated with up to 90% reduction in childhood mortality in poorer settings
How many serotypes of measles?
1
