FUN 11: anti-viral infections
PRRs
TLR 2,4,6 recognise capsid
TLR 3,7,9 recognise DNA/RNA in endosome
RIGI recognises DNA/RNA in cytoplasm
once virus recognised, transcription factors bind to promotor regions to make anti-viral cytokines
IFN alpha + beta
inflamm cytokines also made by NF-Kbeta
IFN
shuts down viral replication in 2 ways...
1) 2'5' oligo A - RNAse L - mRNA degradation
2) protein kinase - inactivation of elf-2 - inhibits formation of protein synthesis start complex
affects immune cells...
both ways activated by dsRNA + use ATP
MHC1 upreg (more CD8 activation)
B cell activation
NK + CD8 activation
dendritic + macrophage activation
Viral Evasion
produce peptides inhibiting IRF 3+7
produces CD59 (prevents complement activation)
mutate (not recognised by MHC1)
interfere with antigen processing
downreg MHC1
! missing self (NKs)
Antibodies
neutralisation: IgG + IgA
opsonisation: IgG1+3
Complement: IgM + IgG1+3
NKs
Antibody dependent cellular cytotoxicity
done by NKs, neutrophils, eosinophils, macrophages
Activated by Fc region + Fc R
make cytotoxic granules
NB anti-viral + anti-tumour immunity
missing self + altered self
cytotoxic (perforin, granzymes, lysis)
release IFN gamma - drives Th1
2 Rs
activatory
inhibitory
binds MHC1 with/without antigen
Resp Syncytial Virus
neonates (esp premature), elderly, immunocompromised
major cause of lower respiratory tract infections (bronchiolitis)
2nd infection more severe
over-inflamm
day 1-3: innate response
day 4-7: cytokine release
day 7-9: adaptive response
treatments...
ribarvarin (anti-viral)
O2 therapy
salbutamol
steroids
Palivizumab given to people @ risk