Interferon

Front 1

intrinsic epithelial barriers to infection

Back 1

mechanical: via tight junctions, flow of air or fluid across it, or movement of mucous via cilia. Chemical: fatty acids of skin, enzymes such as lysozyme (in slaiva, sweat and tears) and pepsin (gut), low pH, antibacterial peptides such as defensins and cryptidins. microbiological elements: normal flora

Front 2

what are some receptors (and their lignads) that induce type 1 interferon.

Back 2

TLR 3 binds dsRNA on PM, TLR 7 binds ssRNA in endosomes, other TLR on PM bind viral glycoproteins, RIG 1 is intracellular and is a helicase that binds dsRNA inside the cell, PKR

Front 3

describe type I and type II interferon.

Back 3

type I is induced directly by viral infection, most types of viral infected cells can synthesize them and they include IFNa and IFNB. Type II interferon is IFNy, and is made only by special immune cells like NK, CD4 TH1s, and CD8s as well as some dendritic cells, they are induced by a mitogenic (cytokine) element or antigenic stimuli on the cell

Front 4

describe the functions of interferons

Back 4

inhibit virus replication, inhibit cell growth (anti tumor), activation of monocyte/mac, NK, CD8s (the adaptive immune response), induct MHC I and II antigens, Fc receptors, and antigen processing machinery. Inhibit nonviral intracellular pathogens, pyrogenic activity

Front 5

describe signalling within the cell with IRF 3 to transactivate IFN type I

Back 5

virus infection causes dsRNA or some other factor like capsid protein to bind a cellular protein to make virus activated kinase which then Pis IRF 3 which can go to the nucleus and associates with some other protein to form DRAF which, with the help of NFKB, act as transactivators for IFNB.

Front 6

what part of viral replication is where most interferon inhibition occurs?

Back 6

level of viral txn and translation

Front 7

wha are the five major antiviral pathways IFN utilizes?

Back 7

dsRNA-dependent PKR pathway, coupled 2'-5' oligoadenylate synthetase/Rnase L pathway, RNA specefic adenosine deaminase pathway, Mx pathyway, and iNOS pathway (IFNy only)

Front 8

describe the dsRNA dependent PKR pathway.

Back 8

PKR has two forms, one is constitutively expressed, other is IFN induced. Inactive PKR dimerizes, auto-pis after dsRNA binds, activated PKR causes intermolecular pi-ing of proteins ( like eIF-2 alpha which would be needed for tsln initation and possibly txn factor inhibitor IKB). PKR is also activated by host PACT (no dsRNA) and this is important in terms of cell replication and normal cycling. PKR is inhibited by host 581PK

Front 9

describe the coupled 2 to 5' OAS/Rnase L pathway.

Back 9

OAS protein is activated in virus infected cells by binding dsRNA and then catalyzes the synthesis of 2'-5' linked oligoadenylates which non speceifically degrades ssRNA and helps in apoptosis of infected cell. Dormant cytosolic Rnase L monomers form active dimers after binding 2-5 A oligoadenylates and then munch on ssRNA helping with apop

Front 10

describe the viral antagonists of the IFN induced proteins.

Back 10

2 classes. Signaling antagonists function by binding ds RNA and masking IFN inducer, binding IFN to block signaling, binding proteins in signal transduction (jak, tyk or stat), bind IRF to block transactivation. Antiviral protein antagonists can function by binding dsRNA to prevent activation, reverse pi-ing of eIF2a, protein binding to PKR and inhibiting activation, RNA binding to PKR and inhibiting activation, oligoadenylate variants that bind to RNaseL. in addition viruses can upregulate endogenous cellular inhibitors of antiviral proteins