interferons Flashcards
what are some examples of intrinsic immunity?
physical barriers
mucus eyelashes skin skin flora saliva
how does your body know a virus is a virus
pathogens have a different ratio of nucleotides i their genome
if there are too many CpGs in their membrane then the host will know that it is a foreign organism and ZAP proteins will degrade the dna
where are type 1 interferon receptors found?
on all cells in the body
what are type 1 interferons?
polypeptides secreted from infected cells
2 types, INF alpha and INF beta
what are the major functions of type 1 interferons?
- Induce antimicrobial state in infected and neighbouring cells
- modulate innate response to promote Ag presentation and NK
- Activate the adaptive immune response
which is the interferon that is secreted first and all cells can make?
INF beta
what are type 2 interferons?
INF gamma
Produced by activated T cells and NK cells
Signals through a different receptor IFNGR.
how does your body differentiate self from non self?
via pathogen associated molecular patterns (PAMPs) which is usually nucleic acid.
eg viral DNA in the cytoplasm is a PAMP as your cell knows that is wrong
pattern recognition receptors are there to see the wrong thing in the wrong place
what are the different pathogen sensors that detect viral DNA?
cytoplasmic RIG-I like receptors RLRs,
-see subtle different versions of RNA (eg RNA withoust a cap on)
endosomal Toll like receptors TLRs
Cytoplasmic nucleotide oligomerization domain receptors NLRs
what is the pathway of RIG-I and RLRS?
activated by unusual rna
bind to Mavs on mitochonria which induces a signalling cascade and production of IFN beta
what is the pathwya of TLRs
found on endosomes
detect viral RNA and induce a signalling cascade which produces IFN alpha (and beta)
what detects viral DNA?
cGAS
activated
activates enzyme which makes a second messenger- cGAMP
this then passes to STING protein found on the ER and this triggers the same downstream messengers that cytoplasmic PAMP dsRNA causes.
IFN 3 goes into the nucleus and sits on the promotor gene for INF beta
describe the process inside a cell after picking up an IFN signal in the receptor
- IFNAR1 and AR2 dimerise and JAK1 and TYK2 cross-phosphorylate.
- STAT proteins are activated and this activates…
a. Antiviral response (ISRE).
b. Inflammatory response (GAS).
c. Repressors of the inflammatory pathways (GAS).
what are examples of interferon stimulated genes to stop viral infection
Protein kinase R causes ribosomes to shut down so the virus cannot utilize them and replicate
inibits viral translation (and cell translation)
IFITM3 – Interferon Induced Transmembrane Protein 3:
-Restricts virus entry through endosomes by stopping them escaping so the virus is broken down by the acidic pH.
locks the virus in the endosome
what differfent ways may a virus evade IFN response
avoid detection by hiding PAMP
Interfere globally with host cell gene expression and/or protein synthesis
Block IFN induction cascades by destroying or binding
Inhibit IFN signalling
Block the action of individual IFN induced antiviral enzymes
Activate SOCS
Replication strategy that is insensitive to IFN
how does Hep C evade IFN control?
makes a NS3/4 protease acts as an antagonist to interferon induction by cleaving MAVs
how does the influenza virus evade interferon control?
makes NS1 proteins
acts as antagonist to interferon induction by binding to RIG-I /TRIM25/RNA complex and preventing activation of signalling pathway, and also prevents nuclear processing of newly induced genes.
how do Pos viruses evade the immune system
they have lard DNA which encode for a lot of accessoty genes that modify the immune response. one is they make soluble cytokine receptor which floats around outside the infected cell
when the infected cell tries to release signalling cytokines, the soluble cytokine receptor will pick it up and prevent signalling
what is the cytokine storm?
when the virus is replicating lots it induces high IFN which has little effect so the body makes more and TNFa and other cytokines which have a more damaging effect than the virus might have had
how may INFs be involved in cancer therapy?
Cancer cells may be deficient in IFN and so if a cancer patient is given a novel virus, the virus can kill the cancer cells whilst the healthy cells produce interferon to combat the virus.
