26. Viral evasion of the adaptive immune response Flashcards
what are 4 things to remember about viruses and immunity interacting?
- every virus has a range of evasion mechanisms and they are all different
- host-virus balance can range from latency and non-cytopathic infection to cytopathic infection
- host responses need to be kept at bay long enough to allow the virus to replicate and infect another host
- a virus is inside the cell most of the time
what is the main viral defence?
the destruction of virally infected cells by CD8+ cells
what are the 4 ways viruses evade adaptive immunity?
- evasion of antibodies
- interference in antigen presentation
- infection of immune system cells
- latency
how do viruses enter host cells?
by binding to a receptor and either receptor mediated endocytosis or membrane fusion
how can antibodies prevent viral entry/infection?
- block the virus from interacting with the receptor - neutralising antibodies
- Prevention of conformational rearrangement once virus is bound
- interference with viral/host membrane fusion by locking virus structure in place
- blocking endocytosis
- prevention of capsule degradation
- antibodies taken up into cells to block other stages of the viral lifecycle
- Aggregation of viruses in the extracellular environment
how can viruses evade the antibody responses?
antigenic variation
steric inaccessibility of the receptor binding site
what 2 ways can the receptor binding site be blocked?
buried sites
glycan shields
how does antigenic variation occur in RNA viruses?
- RNA polymerase/reverse transcriptase has a very high error frequency
- no/limited proofreading ability
how is having no proofreading ability an advantage to the virus?
forms a cloud of quasispecies that allow different viruses within the infection to survive as they are better adapted
antigenic drift in both B and T cells
what happens in viral infection with non-neutralising antibodies?
- leads to virus entry in large amounts for some viruses
- viral advantage
- no selection pressure for the viral so viral proteins don’t need to change
- viral persistence
what could happen in viral infection with neutralising antibodies?
- selection pressure for mutants that can escape antibodies
- infection persistence
- reinfection of acute infection as acquired immunity diminished
what happens in viral infection with T cell recognition with intact epitope?
stays effective if the epitope doesn’t change
clearance of the virus
selection for escape mutants
what makes a T cell escape mutant?
Causes:
impaired processing for MHC presentation
decreases MHC binding
Reduced TCR binding
how can MHC expression be blocked?
if the peptide changes the MHC binding is impaired so antigen presentation is effected and impaired TCR recognition
what could happen if the T cell epitope doesn’t change?
over stimulation and exhaustion of the immune response
- up regulation of certain T cells and function is impaired
- persistent infection or cancer
what determines a viruses ability to evade vaccines and antibodies?
its plasticity
what viruses are not very effective at evading vaccines and antibodies?
not very plastic viruses like measles
means vaccines can last a long time
what causes plasticity?
we don’t know
what does a virus being very plastic mean?
they can change their protein/antigen structure fairly easily
what happens with antigenic variation at a genetic level?
some conserved regions which stay the same
hypervariable regions that are always mutating and changing
hypervariable genetic regions are often at antibody epitopes to make them ineffective
what is antigenic drift?
small mutations changing over time
existing immunity can continue working just not as well
what is antigenic shift?
a large dramatic shift that subverts all previous immunity
what regions tend to be conserved?
receptor binding domains
if these change binding will be affected
