interferons

Question 1

what are some examples of intrinsic immunity?

physical barriers

Answer 1

mucus 
eyelashes 
skin
skin flora 
saliva

Question 2

how does your body know a virus is a virus

Answer 2

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

Question 3

where are type 1 interferon receptors found?

Answer 3

on all cells in the body

Question 4

what are type 1 interferons?

Answer 4

polypeptides secreted from infected cells

2 types, INF alpha and INF beta

Question 5

what are the major functions of type 1 interferons?

Answer 5

1. Induce antimicrobial state in infected and neighbouring cells
2. modulate innate response to promote Ag presentation and NK
3. Activate the adaptive immune response

Question 6

which is the interferon that is secreted first and all cells can make?

Answer 6

INF beta

Question 7

what are type 2 interferons?

Answer 7

INF gamma
Produced by activated T cells and NK cells
Signals through a different receptor IFNGR.

Question 8

how does your body differentiate self from non self?

Answer 8

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

Question 9

what are the different pathogen sensors that detect viral DNA?

Answer 9

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

Question 10

what is the pathway of RIG-I and RLRS?

Answer 10

activated by unusual rna

bind to Mavs on mitochonria which induces a signalling cascade and production of IFN beta

Question 11

what is the pathwya of TLRs

Answer 11

found on endosomes

detect viral RNA and induce a signalling cascade which produces IFN alpha (and beta)

Question 12

what detects viral DNA?

Answer 12

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

Question 13

describe the process inside a cell after picking up an IFN signal in the receptor

Answer 13

1. IFNAR1 and AR2 dimerise and JAK1 and TYK2 cross-phosphorylate.
2. STAT proteins are activated and this activates…
   a. Antiviral response (ISRE).
   b. Inflammatory response (GAS).
   c. Repressors of the inflammatory pathways (GAS).

Question 14

what are examples of interferon stimulated genes to stop viral infection

Answer 14

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

Question 15

what differfent ways may a virus evade IFN response

Answer 15

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

Question 16

how does Hep C evade IFN control?

Answer 16

makes a NS3/4 protease acts as an antagonist to interferon induction by cleaving MAVs

Question 17

how does the influenza virus evade interferon control?

Answer 17

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.

Question 18

how do Pos viruses evade the immune system

Answer 18

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

Question 19

what is the cytokine storm?

Answer 19

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

Question 20

how may INFs be involved in cancer therapy?

Answer 20

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.