Interferon Flashcards
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 polypeptide factor produced and secreted from cells 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?
IFN beta
Which cells produce IFN beta?
All cells produce IFN beta and all tissues have IFNAR receptors
What is IFN beta induction triggered by?
IRF-3
Name a cell type that is specialised for producing IFN alpha.
Plasmacytoid dendritic cells
What do Plasmacytoid dendritic cells express high levels of?
IRF-7
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 type II IFN?
Produced by activated T cells and NK cells
Which receptor do these type II IFN signal through?
IFNGR
Which IFN falls under type III IFN?
IFN-lambda
Which receptors do type III IFNs signal through?
IL-28 receptors IL-10 beta receptors
Where are the receptors for type III inteferons mainly present?
Epithelial surfaces E.g. respiratory epithelium and gut
Which organ is IFN lambda very important in?
Liver
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 Both examples of PRRs
Describe RIG-I signalling.
RIG-I like receptors will recognise single stranded RNA in the cytoplasm of the cell It will signal through MAVS (mitochondrial) This will signal further downstream, leading to phosphorylation of IRF3 and IRF7 Theses will dimerise and enter the nucleus to act as a transcription factor Leads to the generation of IFN-beta transcripts Note: Mavs may also activate pathways leading to NFkB activation or Jun kinase activation

Describe TLR signalling.
- TLR detects nucleic acids in the endosome (this isn’t normal) or outside the cell
- It will signal to one of 2 molecules outside the endosome
- MyD88 or Trif
- Trif activates IRF3
- Myd88 activates NFkB and IRF7
- It will result in the switching on of expression of INF alpha and beta

Describe DNA sensing.
- Mainly done by cGAS
- This is an enzyme that binds to dsDNA in the cytoplasm
- Then synthesises cGAMP (second messenger)
- cGAMP diffuses to STING (found on endoplasmic reticulum)
- This triggers phosphorylation of IRF-3
- which then dimerises and acts as a transcription factor


