Flashcards in Interferon Deck (53)
What is the most common cause of sporadic encephalitis worldwide?
Herpes simplex encephalitis
Which subset of the population is herpes encephalitis most common in?
Most common in childhood – affecting previously healthy individuals on primary infection with HSV-1
What is interferon?
Transferrable factor produced when the cells are exposed to virus
What is the effect of interferon binding to interferon receptors on cells?
It binds to specific receptors and signals the de novo transcription of hundreds of interferon stimulated genes (ISG)
What are the three functions of type I interferons?
Induce antimicrobial state in infected and neighbouring cells
Modulate innate immune response to promote antigen presentation and NK cells but inhibit proinflammation
Activate the adaptive immune response
What are the type I interferons?
IFN alpha and IFN beta
What is the first interferon to be produced in a viral infection?
Which cells produce IFN beta?
All cells produce IFN beta and all tissues have IFNAR receptors
What is IFN beta induction triggered by?
Name a cell type that is specialised for producing IFN alpha.
Plasmacytoid dendritic cells
What do these cells express high levels of?
How many genes are there for IFN alpha and IFN beta?
Alpha – 13/14 isotypes
Beta – ONE
Which IFN comes under type II interferon?
IFN-gamma - specialist immune signalling molecule
Which cell types produce this IFN?
Produced by activated T cells and NK cells
Which receptor do these IFNs signal through?
Which IFN falls under type III IFN?
Which receptors do type III IFNs signal through?
IL-10 beta receptors
Where are these receptors mainly present?
E.g. respiratory epithelium and gut
Which organ is IFN lambda very important in?
How does the innate immune system recognise non-self?
PRRs (pattern recognition receptors) on innate immune cells recognise
PAMPs (pathogen-associated molecular patterns)
NOTE: they often sense nucleic acids
Name two receptors that are involved in detecting the presence of viruses and state where they are found.
RIG-I like receptor (RLRs) – cytoplasmic
Toll-like receptors (TLRs) – plasma membrane + endosomal membrane
Describe RIG-I signalling.
RIG-I like receptors will recognise single stranded RNA in the cytoplasm of the cell and it will signal through MAVS (mitochondrial)
This will signal further downstream, leading to generation of IFN-beta transcripts
Describe TLR signalling.
TLR detects nucleic acids in the endosome (this isn’t normal)
It will signal to molecules outside the endosome (MyD88) and send various transcription factors to the nucleus
It will result in the switching on of expression of IFN alpha
Describe DNA sensing.
Mainly done by cGAS
This is an enzyme that binds to dsDNA in the cytoplasm and synthesises cGAMP (second messenger)
cGAMP diffuses to STING (found on endoplasmic reticulum)
This triggers phosphorylation of the same sets of transcription factors and signalling molecules the RNA viruses were triggering
Describe the structure of IFN receptors for IFN alpha and IFN beta
They are heterodimers of IFNAR 1 and IFNAR 2
Describe the signalling from IFNAR receptors
IFN binds and the IFN receptor activates Jak and Tyk, which goes on to phosphorylate the STAT molecules
STAT molecules dimerise and combine with IRF-9
It then goes to the nucleus, binds to a promoter and regulates transcription
What is IFITM3?
Interferon-induced transmembrane protein 3
These sit on the membrane of endosomes, in cells that have been previously stimulated by IFN
It prevents fusion of the virus membrane with the endosomal membrane so the virus gets trapped in the endosome
NOTE: mice and people lacking IFITM3 get more severe influenza
What are Mx1 and Mx2?
GTPases with a homology to dynamin
Mx can form multimers that wrap around nucleocapsids of incoming viruses – this nullifies the viral genomes
Mx1 – inhibits influenza
Mx2 – inhibits HIV
Describe the actions of Protein Kinase R.
It phosphorylates the alpha subunit of eIF2 (initiation factor) that is important in translation
This prevents ribosomes from binding to mRNA so NO NEW GENES WILL BE TRANSLATED
It also phosphorylates NFkB, which is an important transcription factor that is part of the interferon and inflammatory response