Micro 6: viral evasion of host immunity Flashcards
Why are all viruses sensititve to T cells?
because obligate parasites-their proteins can be picked up by MHC class I and present them to T cells-> cell killed before they can replicate The antigens presented are any internal viral proteins (enzymes, etc) and they vary a lot less than surface Ag--> can be even shared in several viruses => need to be able to actually avoid the surveillance (like herpes, which can stay you whole life)
Describe the process of MHC I antigen presentation? What is the roll of viruses here?
Proteins are picked and targetted via the proteasome-> then via tap transporter to the ER. There picked up by MHC i-> golgi-> cell surface where theya re presented
Tcells will surveil all the cells, and if it sees a peptide that stimulates it -> liberate perforin and other -> kill cell
all these steps and more are targetted by viruses
eg; herpes virus stops the TAP transporter
adenovirus stops the transcription oh MHC I
balance between the invasion and the immune system
How does EBV, HSV, CMV, adenovirus, KSHV avoid immune system?
EBV-EBNA1 has weird glycine residues that cannot be targetted by the proteasome,
HSV stops TAP from working
Cytomegalovirus-stops ATP binding TAP and translocating
CMV also binds tapason and prevent loading on MHC
Adernovirus presents MHC to move to golgi
Which viruses block MHC presentation
KSHV (another herpes virus)–ubiquitinylation of MHC-> internalisation -> degradation
How does human papillomavirus prevent recognition
counters innate and cellular immune prevent innate -> E7 and E6 stops STING singaling in interferon pathway E5 protein prevents MHC class I presentation to the cell surface
How do viruses avoid NK killing via the missing self mechanism
If a cell doenst have MHC (any)-will be targetted and killed by NK
Some viruses have encoded for MHC analogues-stuck in the cell surface and non act as missing
CMV does that –looks like they have MHC
If not preventing the MHC pathway, how does measle stop the immune system?>
Measle infects CD150 (SLAM) cell (immune cells)-including memory T lymphocytes-> erases cellular memory
Patients can be very sensitive for 2-3 years after to virus theyve already have
So its a form of immunosupression–why vaccine is so important
How do viruses avoid the antibody response of the body?
Most vaccine want to create AB against surface Ag-> stop virus from doing anything
Most common way to avoid-antigenic variance-change Ag all the time so the Ab cant recognise
Influenza-antigenic drift (Ab drives the change)
HIV-quasispecies (so long to replicate that many forms of surface Ag develop in one person
Antigenic shift-induction of new subtype from animal sources (look very different from what human immune system is used too)
lastly: Rhinovirus just has so many serotypes that its unlikely you catch the same one again. Means for some vaccinations need to be sure you include all serotypes (polio-3sero, dengue-4sero)
What is antigenic drift and its role in influenza?
If Ab can block a virus from replicating/entering cell-> will die
Usually Ab bind hemagglutinin (the spikes on viruses)-the tip of these (head domain) tend to vary between everyvirus. tail vary less
Error prone viral polymerases-only fittest mutants will survive-> which are the ones with different HA heads-> suddently our Ab are not useful
why need to develop a vaccine every year–and have to guess-can get it wrong
Can it be possible to avoid angtigenic drift?
well our AB liked to target the head of HA-but that changes
the stem doesnt change as much–and some Ab can target it
unsure if it doesnt change because its not targetted as much or if it cant change
So if can induce/create Ab against the stem-can bind all AG-universal vaccine
Maybe form a headless HA vaccine-can only bind that
Or glycosylating the HA head domain-cant be targetted
Display the HA differently-stem more visible
=> none of them are working at the moment
Why is HIV very resistant to the immune system?
HIV spikes (Gbp120) are very seperate from one another--prevent Ab crosslinking-cant activate much Important parts of the molecule are poorly acessible (like CD4 targetting protein)
Can we create an HIV vaccine?
Some peope do produce Ab targetting the stem of the spikes and work against several HIV serotypes
But how do synthestically convice someones system to do that?
Also as you produce and have these Ab, HIV will change and quickly avoid them
Why is rhinovirus not have a vaccine?
Just too many serotypes-cant do it–too much
Why is poliovirus vaccine different from an average one?
need to target all 3 serotypes or else youd still have polio
The live attenuated-need all 3 to infect you, but some serotypes are better than other-this vaccine wouldnt provide protection to all 3 all the time
1 serotype has been entirely eradicated now
and new vaccine doesnt depend on infection
What is the dengue virus? What disease does it cause and why? Why is vaccinating against dengue dangerous?
Dengue has 4 serotypes–1st time u get it-fever/flu like
but the second time-cytokine storm can cause heammorhagic fever
this happens because in the first infection can create good Ab that neutrolise the serotypes. But second infection, the Ab can bind the Ag, but not alawys neutralise (if other serotypes)–> AB+Virus complex will bind Ab receptors, and the virus will be able to infects a lot more cell-immune cells especially =>Ab dependant enhancement of disease
Virus is now protected from DAMPs and PAMPs, and cause production of way too much cytokines
if vaccine misses a serotypes->actually accelerate chances to get heammorghagic fever because immune system primed
