viral infections Flashcards
viral evasion of host immunity: explain how viruses escape host innate and cellular immune mechanisms and recall examples
significance of viral (obligate IC parasite) proteins being easy targets
processed and presented by MHC class I, with internal viral proteins being possible targets of cellular immunity as they vary less than surface antigens
effect of cellular immunity on viral infection
cellular immunity clears viral infection but is short lived, so viruses that persist must evade cellular immunity (e.g. herpes viruses)
give pathway of MHC class I antigen presentation
viral peptide synthesised inside infected cell -> chopped by proteosome -> into ER -> picked up by MHC class I molecules -> transport up to Golgi and membrane -> present peptides to CTLs
example of viral regulation of MHC class I antigen presentation
encode proteins which stop transporter being able to put foreign peptides into ER for MHC class I presentation
mechanisms to prevent viral regulation of MHC class I antigen presentation
evasion of antigen loading to tapasin from cytoplasm to ER lumen, modulation of TAP function and prevention of MHC transport, interfering with MHC presentation at cell surface
evasion of antigen loading to TAP: CBV, HSV and CMV
CBV: cannot be processed by proteasome, HSV: processed peptide has blocked access to TAP, CMV: ATP stops binding to TAP (preventing translocation)
modulation of tapasin function and prevention of MHC transport: CMV and adenovirus
CMV: binds tapasin to prevent peptides being loaded to MHC, adenovirus: prevention of recruitment of TAP to tapasin (and retention of MHC in endoplasmic reticulum)
interfering with MHC presentation at cell surface: KSHV
KSHV: induces polyubiquitinylation and internalisation of MHC (from internalised endosome, MHC passed to lysosomes where it is degraded)
describe how viruses avoid natural killing
miss self mechanism: normal healthy cells display MHC at their surface, and any cells that don’t display MHC are detected by NK cells and killed, so viruses encode MHC analogues or upregulate MHC to avoid NK destruction
describe antigenic variation and sources
continued rapid evolution driven by antigenic pressure from host (e.g. influenza antigenic drift, HIV quasispecies), or introduction of new subtypes from animal source (e.g. influenza antigenic shift), or viruses which exist as different genetically stable sterotypes (e.g. rhinovirus)
what is the major antigen of a virus, and properties
haemagglutinin, which has a very variable head domain (evolves all time), and a less variable stalk domain
consequence on vaccines of antigenic drift
vaccines updated every year to best represent circulating strains due to evolution of variable head, mapped by anitgen cartography (can get it wrong if selected strain is poor match with predominating circulating virus)
due to head variability, what do most broadly neutralising (bn) antibodies target
haemagglutinin stalk, as these are constant (basis for a “universal virus antibody)
3 ways to skewer antibody response towards haemagglutinin2 stalk region
headless haemagglutinin, hyperglycosylating haemagglutinin1 head domain, peptides against fusion peptide and ectodomain, make haemagglutinin stem more spread out (e.g. ferritin based nanoparticles), sequential immunisation with chimeric haemagglutinin
describe 4 ways by which HIV resists neutralisation by antibodies
large spaces between haemagglutinin spikes to prevent antibody crosslinking, extensive glycosylation to mask antibody epitopes, poorly accessible functionally important parts of molecule, huge variation in redundant amino acids against highly specific antibodies
describe broadly neutralising antibodies to HIV in some infected people
control viral load as antibodies can cross react with many HIV strains by binding to stalk region
negative aspect of broadly neutralising antibodies which control viral load
viruses evolve and produce escape mutants
what virus causes common cold, and consequence of vaccine production
human rhinovirus (exists as hundreds of antigenically distinct serotypes that co-circulate, so impossible to make vaccine against them all)
number of serotypes of poliovirus, and consequence of vaccine (Sabin, not Salk) production
3, so with Sabin vaccine must have administration of all 3 at once (one serotype may be outcompeted for replication, so poor response requiring larger dose for this serotype in vaccine)
Dengue (arbovirus) feature and detection
4 serotypes, and if infected twice, becomes Dengue haemorrhagic fever, with a cytokine storm with leakage of blood plasma from capillaries (detected by increased RBC and decreased blood protein)
Dengue haemmorhagic fever signs and treatment
tendency to severe bruising and bleeding, with deterioration even after fever drops (shock so treat with i.v. fluid replacement)
describe how Dengue virus can cause Dengue haemorrhagic fever
so antibody generated against previous infection can bind but not neutralise, forming immune complexes of virus and antibody, which are picked up by Fc receptor on macrophages, leading to antibody dependent enhancement (can infect other cells including macrophages), causing Dengue haemorrhagic fever (new infected immune cells produce cytokine storm with many pro-inflammatory molecules)
consequence of vaccination on Dengue virus
must target all 4 serotypes and neutralise, preventing Dengue haemorrhagic fever
describe virus-mediated immunosuppression
some viruses (e.g. measles) infect memory lymphocytes, so cause a decrease in immunological memory, so are more susceptible to other infections also
