Immunity to COVID 19 Flashcards
what is the structure of COVID19
positive strand RNA virus
spike glycoprotein
envelope
where did the delta variant originate from
india 2021
where did the gamma variant originate from
brazil 2021
where did the alpha variant originate from
UK 2020
where did the omicron variant originate from
south africa
what change does N501Y denote
asparagine to tyrosine at position 501 of spike protein
what differences does the omicron varient have
less efficient at replicating in lung epithelia
lower levels in LRT
shorter incubation period
less hospitalisations
how do variants emerge
natural selection and persistent infection
what is the closest relative to SARSCOV2
RaTG13 96% in bats
what fuses virus with host cell membrane
TMPRSS2 and FURIN
omicron doesnt bind well
how does the innate system respond to covid
TLR7/8 senses ssRNA TLR3 senses dsRNA intermediates RIG1/MDA5 - cytoplasmic viral RNA inflammasome activated cytokines and interferons produced
what transcription factors cause production of cytokines and interferons
NFKB, IRF3, IRF7
what is a prominant immune feature of COVID19
impaired interferon response - antagonistic mechanisms agaist IFN signalling
how does severe infection with SARS-CoV-2 effect B cell response
induces a robust extrafollicular
response but an impaired germinal centre (GC) B cell response in some individuals
how do COVID19 variants effect t cell immune response
they do not - recognise conserved peptides on spike protein
Characteristics of Immune Response in severe COVID-19 patients
Acute Respiratory Distress Syndrome (ARDS)
increased IL-6, IL-8, TNFα and IP10 (chemokine)
cytokine storm
immature neutrophils
exhausted NK and DC
t cell lymphopenia
what do excessive amounts of pro inflammatory molecules do
promote vascular permeability and organ damage, hypercaogulation
lab tests that indicate severe infection
high IL6, IL8, TNFa, IP10 high CRP high D dimer high neutrophils low lymphocytes
Immunomodulatory Treatment Options
Monoclonal Antibody drugs can block the effect of
cytokines such as IL-6, IL-8, TNFα
Glucocorticoids (Dexamethasone & Prednisolene) are powerful, broad-active
immunosuppressive drugs - NF-kB
what is Merck
RNA dependent RNA polymerase inhibitor
what is Paxlovid
SARS COV 2 protease inhibitor
what type of vaccines are moderna and pfizer
DNA and RNA
what type of vaccine is novavax
subunit
what type of vaccine is astrazenaca and janssen
viral vector
how do some vaccines change spike protein
keep it in prefusion standing up conformation
features of mRNA vaccine design
Nucleotide modification: substitution of Uridine for Pseudouridine- Protects the mRNA from nuclease degradation
Use of preferred codons for translation in human cells
what protects mRNA to deliver it through PM
lipid nano particles
