Interferon Flashcards
what is the most common cause of sporadic encephalitis in the western world?
- herpes simplex encephalitis
- most common in childhood
what are the 6 genes that are implicated with inborn errors in HSE?
- TLR3
- UNC(3B1
- TRIF
- TRAF3
- TBK1
- IRF3
what do these gene errors do?
- impairs CNS intrinsic interferon alpha/beta response to HS infection
- virus replicated to a much higher extend than would be otherwise
what is interferon?
transferable factor produced when cells are exposed to virus
what does interferon do?
- binds to specific receptors
- signals activation of de novo transcription of hundreds of interferon stimulated genes
- puts cell into an anti-viral state
what are type 1 interferons?
polypeptides secreted from infected cells
what are the 3 main functions of type 1 interferons?
- induce antimicrobial state in infected and neighbouring cells
- modulate innate response
- promotes antigen presentation and NK cells
- inhibits proinflammation
- activate adaptive immune response
what is the first interferon to be made?
- IFN beta
describe how type 1 interferons cause adaptive immune response
- cells sense viral infection
- make an interferon response
- results in synthesis of new copies of IFN-beta
- IFN beta can diffuse and interact w/ receptors on neighbouring cells
- switches on genes in neighbouring cells switches them into anti-viral state
- recruits APCs and adaptive immune cells
what are specialized cells that are good at making interferon?
- plasmacytoid dendritic cells
- particularly IFN-alpha
what are the type 1 interferons? what are they secreted from?
- IFN alpha/beta
- IFN beta secreted by ALL cells
- IFN beta induction triggered by IRF-3
where is the IFNAR receptor?
present on all tissues
how many genes are there for IFN alpha/beta?
- one gene for IFN-beta
- 13/14 isotypes of IFN-alpha
what is type 2 interferon? What produces it?
- much more specialist immune signalling molecule
- produced by immune cells (activated cells, NK cells)
- signals through IFNGR
what is type 3 interferon? where is it present?
- IFN lambda
- mainly on epithelial cells
what does type 3 interferon signal through?
- IL28 receptor
- IL10 beta
what does IFN lambda do?
- protects barriers of your body e.g. resp epithelium, gut
- important in liver
what are polymorphisms in IFN lambda gene associated with?
different outcomes from liver viruses
how do you differentiate self from non self?
- PAMPs
- PRRs
- often sense foreign nucleic acids
what are the receptors for sensing the presence of viruses?
- RLRs (cytoplasmic RIG-1 like receptors)
- TLRs (endosomal toll like receptors)
- cytoplasmic nucleotide oligomerisation domain receptors (NLRs)
describe TLRs
membrane proteins
found on plasma membrane and on endosomal membranes
describe RLRs
sense virus in cytoplasm
signal through a mitochondrial located pathway
which is the most famous DNA sensor?
cGAS
signals to a molecule called STING found on ER
describe the steps to interferon induction
- PRRs (e.g. RIG-1 like receptors) detect PAMPs
- RIG-1 then signal through Mavs on mitochondria
- this triggers signalling through pathways
- results in translocation of molecules from cytoplasm to nucleus
- TFs become phosphorylated
- bind to promoter regions of target genes (e.g. IFN beta)
- will generate IFN beta transcripts