Immune response to virus infection Flashcards
what antiviral cytokines do infected cells and plasmacytoid dendritic cells produce?
type I interferons alphas and beta
How do plasmacytoid dendritic cells detect viral nucleic acids?
TLR7 and TLR9
How do infected cells detect viral nucleic acids?
RIG-I and Mda-5
What to IFN alpha and bets do?
inhibit viral replication by inducing ezpression of:
dsRNA activated protein kinase (PKR)
oligoadenylate synthetase
how does PKR work to inhibit viral replication?
activated by dsRNA
inactivation of eIF-2alpha (translation factor)
inhibition of protein synthesis
How does oligoadenylate synthetase work?
activated by dsRNA
activates RNAse L
degradation of viral RNA
How do IFN alpha and beta facilitate immune response to viral infection/
promote expression of MHC class I
produce NK cells increasing cytotoxic activity
What are NK cells?
lymphocytes
granular morphology
recruited to viral infected sites
important role in early stages before CTLs
How do NK cells recognised virally infected cells?
- lack specific receptors
- express germ-line encoded receptors
- stress induce expression of ligands for NK activating receptors - NKG2D receptors, UL16 binding proteins, MICA/B
- virus downregulate MHC class I expression
What ligands are present that cause cells to be killed by NK cells?
NKG2D
What happens if cell lacks MHC class I?
Killed by NK cells lose MHC class I = lose inhibitory signal
Why is there a balance between expression of certain ligands and downregulation of MHC class I?
balance will determine HOW the NK cells kill the target cell
How do the contents of NK cells induce apoptosis?
granzymes
perforin - pores in membranes, granzymes can enter into cell cytoplasm and induce apoptosis
How do NK cells connect to the target cell?
form a lytic immunological synapse - polarise at synapse
How to granzymes from NK cells act?
DNA fragmentation - capsase activated DNAse
mitochondrial dysfunction
cleave proteins
targets pro-capsase 3