viral evasion of host immunity Flashcards
what are viruses and what are they represented by?
- intracellular pathogens
- represented by MHC 1 mech
what clears viral infection? What can be targets?
- cellular immunity clears viral infections but short lived
- interval viral proteins can be targets of this as they vary less than surface antigens
name an evading virus
herpes simplex virus
state 3 ways a virus can evade MHC
- evasion of antigen loading to TAP
- modulation of tapasin function and prevention of MHC transport
- interfering with MHC presentation at cell surface
explain how 3 viruses evade their antigen being loaded to TAP (transporter associated with antigen processing)
- EBV: EBNA1 cannot be proteasome
- HSV: ICP47 blocks access of processes peptide to TAP
- CMV: US6 stops ATP binding to TAP so prevents translocation
explain how 2 viruses modulate tapasin function and prevent MHC transport
CMV: US3 binds tapasin and prevents peptides being loaded to MHC
Adenovirus: E3-19K prevents recruitment of TAP to Tapasin, retains MHC in ER
what does tapasin do?
- plays important role in stable assembly of class I molecules with peptide
explain how 1 virus interfere with MHC presentation at cell surface
- KSHV: kK3 protein induces polyubiquitinylation at internalization of MHC
- from internalized endosome, MHC is passed to lysosomes
describe the NK killing evasion
- normal healthy cell display MHC at surface
- cells that don’t display MHC are detected by NK cells –> killed
- viruses that disrupt MHC presentation would end up being killed by NK cells
- viruses can encode MHC analogues or upregulate MHC
who does CMV infect?
- only immunocompromised
- problem for transplant recipients
- virus needs to be eliminated from bone marrow cells of transplant recipient before transplantaion
what does antigenic variation occur due to?
- continued rapid evolution driven by antigenic pressure from host
- introduction of new subtypes from animal sources
- existing as a different stable serotypes that co-circulate in humans
- consequence of vaccination
give an example when continued rapid evolution driven by antigenic pressure from host leads to variation
influenza antigenic drift
what is antigenic drift?
change of antigens on a virus picked up from an infected cell that give it immunity to antibodies formed against old self
give an example when introduction of new subtypes from animal sources cause variation
influenza antigenic shift
name 2 viruses that exist as different stable serotypes
- rhinovirus (100s of serotypes): common cold, impossible to make vaccine
- Poliovirus (3 serotypes): one serotype completely eradicated, vaccine still trivalent
- dengue (4 serotypes)
what are broadly neutralizing antibodies?
- produced as biological therapies
- can control viral load
- controls viral load but mutants do appear over time if used individually
what does dengue fever cause?
- leakage of blood plasma from capillaries
- leads to inc. haematocrit and RBC count
- dec. protein count in blood
- causes severe bruising and bleeding
- patietns deteriorate even after fever due to shock
how do you treat dengue fever?
IV fluids
what is antibody dependent enhancement?
- dengue exists as 4 serotypes
- antibodies generated against previous infection can bind but not neutralise
- leads to ADE
- causes dengue haemorrhagic fever
- dengue viruses use ab as an access into monocyte and reproduce inside them
state the 3 mechanisms of evasion of antibody response
- glycoprotein antigens
- apoptotic body disguise
- viral filaments
describe how glycoprotein antigens leas to evasion of antibody response
heavily glycosylated that antibody access is hindered e.g. HIV
describe how apoptotic body disguise leads to evasion of antibody response
- ebola virus particle membranes have high phosphatidl serien lipid content
- makes them look like apoptotic bodies
- taken up by micropinocytosis
- hidden from immune system
how does ebola evade innate immune system?
VP35 and VP24 stops innate immune system from seeing Ebola
how does ebola evade acquired immune sstem?
- ebola acts as apoptoptic bodies
- taken up and hidden
- also synthesizes soluble GPS to act as antibody decoys (sGPs)
- sGPs are immunosuppressive and inhibit neutrophils
what does measles infect?
- CD150+ cells and memory lymphocytes
- erase immunological memory
what can a measles infection result in?
2-3 year dec. in immunological memory
morbidity and mortality from other diseases
what could the structure of the universal influenza vaccine?
- if we can make an antibody against haemagglutin 2 regions (conserved region)
- then we could theoretically be immune as it’s just the variable region that mutates
= broadly neutralizing antibody
