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
What causes dendritic cells mature?
Danger signal e.g. viral nucleic acid via TLR3
Where do dendritic cells move from and to?
originally in periphery e.g. skin, mucosa
move to lymphoid organs - present antigens to T cells & express co-stimulatory molecules
What is the only cell that can present antigen to naive T cells?
Dendritic cell
What are the 2 types of cells that are made from clonal expansion?
Effector cells
Memory cells
How do CTLs detect virally infected cells?
T cell receptor recognises peptides bound by MHC class I
only 1-3 complexes needed for detection
How is MHC class I antigen presented inc ells?
viral antigens chopped by proteasome complex
translocated in ER
MHC class I folding
TAP association & peptide binding
loaded into MHC class I molecules
How do CTLs kill infected cells?
forms immunological synapse
secretory lysosomes polarise to synapse
release perforin & granzymes
ESSENTIALLY SAME AS NK CELLS
What cells secrete antibodies?
- B lymphocytes
- plasma B-cells
What are the antiviral activities of antibodies?
neutralisation
opsinisation
complement activation
How do antibodies neutralise viruses?
bind to proteins on virus surface - prevents receptor binding on host cells
neutralise IgA antibodies in mucus - prevent virus infections
How do antibodies opsinise viruses?
Fc receptor bind to Fc region of antibody-antigen complexes
Phagocytosis of immunoglobulin
How do antibodies undergo complement activation
recruit complement proteins
complement-mediated neutralisation
complement-mediated virolysis
phagocytosis via complement receptors
How do vaccines protect against pathogens?
viral antigens in attenuated or killed form
induction of memory cells
What are the ways viruses evade the immune system?
- interference with IFN alpha and beta
- inhibition of NK cell recognition
- inhibition of CTL recognition
- inhibition of complement activation
How do viruses inhibit the IFN alpha and beta response?
Lassa virus - removes the stimulus for activation, dsRNA
Adenovirus - inhibits IFN transcription
Vaccina - binds to IFN alpha - cannot bind to receptors
How do viruses inhibit NK cell recognition?
HCMV - UL16 blocks expression of NK cell ligands - stay inside cell e.g. MICA
KSHV downregulates cell surface expression of MICA and MICB
How do viruses inhibit presentation of MHC class I?
If peptides do not get into ER, they cannot be loaded onto MHC class I
How do viruses inhibit complement activation?
Complement control proteins are encoded by host cells to prevent damage
KSHC generates own - impair complement activation & complement mediated manage to membrane
KCP - inhibits complement mediate lysis of KSHV virions
