viral evasion Flashcards
what are the different mechanisms viruses use to evade host immunity
MHC evasion NK killing evasion antigenic variation: -shift, -drift, -different serotypes resisting neutralisation antibody dependant enhancement evasion of antibody response erase immunological memory
how are viruses regulated
represented via MHC 1 mechanisms
cellular immunity clears viral infection
what is MCH evasion and give an example of a pathogen that uses this mechanism
MHC evasion:
-evasion of antigen loading to TAP-eg:
oCMV- US6 stops ATP binding to TAP
oEBV cannot be processed by proteasome
-modulation of Tapasin function + prevention of MHC transport- eg:
o CMV- US3 binds Tapasinand prevents peptides being loaded to MHC
o Adenovirus E3-19K prevents recruitment of TAP to tapasin and retains MHC in ER
-interfering with MHC presentation at cell surface, eg:
o KSHV- KK3 protein induces polyubiquitinylation and internalisation of MHC- MHC is passed to lysosomes
explain the process of MHC loading
proteasome breaks up the Foreign peptides and transported via TAP protein into endoplasmic reticulum–>loaded onto MHC class I to be presented to T cells
tapasin helps load antigen onto MHC
what is meant by NK killing evasion and give examples
normal cells display MHC at surface, cells that don’t are detected by NK cells “Missing Self”
viruses that disrupt MHC would end up being killed by NK cells, so some viruses encode MHC analogues, eg: CMV
or they up regulate MHC
what do you need to do to bone marrow before transplantation
you need to remove the CMV as it infects up to 60-90% of people and is a problem in immunocompromised people
this is done by treating the cells with vincristine so the infected cells have toxic molecules build up in them and die (as the infected cells have already lost the transported for toxic substances out of the cell)
what is meant by antigenic variation and how do viruses use it to evade host immune response
continued rapid evolution driven by antigenic pressure from host.
eg
-antigenic DRIFT: change of virus antigens that give it immunity to antibodies formed against its old self- eg influenza, which is why we need new vaccines every year
- Antigenic SHIFT: formation of new subtypes from animal sources eg swine flu, bird flu
- existing as different serotypes that co-circulate in humans- eg: Rhinovirus has 100s of serotypes
how does HIV evade the antibody response
HIV resists neutralisation by antibodies by:
- large spaces between spikes so Abs cannot cross link
- extensive glycosylation masks Ab epitopes
- functionally important parts of antigen are poorly accessible- ie CD4 binding site
how many serotypes of dengue fever
4 serotypes
how do antibodies from previous infection respond to new dengue infections
the antibodies generated by previous infections can bind but not neutralise the new dengue viruses
this leads to Antibody dependant enhancement (ADE) –> causes dengue haemorrhagic fever
they do this as dengue uses the Ab as an access to monocytes and reproduce inside them
give an example of evasion of antibody response by viruses
heavy glycosylation of Antigen- antibody access is hindered- HIV
Apoptopic body disguise- EBOLA membranes have high phosphodatyl serine lipid content that makes them look like apoptotic cells so are taken up by micropinocytosis- hidden from immune system
give an example of a virus that erases immunological memory
measles: vaccine had much larger impact than originally thought because measles infects CD150+ cells (including memory lymphocytes) and thus erases immunological memory which results in a 2-3 year decrease in immune memory- morbidity/mortaliy from other diseases
ebola innate evasion
VP35 and VP24 prevent interferon release and stop innate immune system from seeing ebola
what is a broadly neutralising antibody and give an example
antibody that is effective against multiple strains of a virus
Eg: targeting HA2 in influenza (the conserved part)
