Term
|
Definition
| proteins produced by cells in response to natural virus, bacteria, etc artificial Inducers |
|
|
Term
| which type of viruses (DNA or RNA) affected more by Interferons? |
|
Definition
| RNA viruses are affected more |
|
|
Term
|
Definition
| Ifn is a natural protein (one type is glycosylated, but the others are not), and it is immunogenic. It establishes an antiviral state in cells that come into contact with it these cells become non-infectable. Ifns are heat stable and are not cellular specific (can be produced by one cell type and act on another type). However, they are SPECIES SPECIFIC. |
|
|
Term
| Name the parts of the Ifn system |
|
Definition
| The IFN system has 2 parts: 1) induction: IFN is excreted in protein 2) binding of cellular receptors which activate signal transduction cascades |
|
|
Term
Describe the Genes of the IFn.
What happens with the Ds RNA? |
|
Definition
Genes for Ifn are usually silent. Ds RNA usually causes the Ifn gene to be upregulated.
When a virus infects a cell , there is usually ds RNA production to produce Ifn, that is secreted to other cells. Enough Ifn will be produced to mute the infection.
polyIC is a synthetic RNA molecule that can be used to induce Ifn synthesis.
Mechanism: IFN binds receptor activates tyrosine kinase phosphorylation of 3 proteins occurs these assemble into a transcriptional factor activates IFN inducible genes |
|
|
Term
| 3 canidates for antiviral proteins: |
|
Definition
3 canidates for antiviral proteins:
Protein kinase is synthesized by protein kinase synthetase. Ifn increases protein kinase levels in the cell. It is only effective when it binds dsRNA. The protein kinase then becomes active, and phosphorylates a eukaryotic initiation factor called EIF-2. EIF-2 has to be present and active to produce a polypeptide for a transcript. Phosphorylation inactivates EIF-2 inhibition of protein synthesis.
Adenovirus produces a protein that binds to the kinase to prevent it from binding dsRNA.
Reovirus has a large ds RNA genome. We would expect it to be a good Ifn inducer. However, it produces a protein that binds to its own ds RNA, so that protein kinase cannot bind.
HIV infection downregulates protein kinase activity.
Poliovirus has an enzyme that degrades protein kinase.
The real name of the protein kinase is PI-EIF-2 alpha protein kinase (this is our cellular response to the virus).
Oligo 25A andenylate synthase causes increased production of oligo 25A in cells from ATP. Oligo 25A binds RNAase L, to activate the enzyme viral mRNA is degraded and viral proteins cannot be produced.
MX protein: cells containing MX gene are resistant to influenza virus infection. It is thought to work through the Ifn cascade, but we are not sure how exactly.
Ifn genes are related to the cytokine family. Ifn gamma can modulate the immune response. Ifn inhibits cell growth and has cytotoxicity.
Ifn is effective against HepB, lymphogeal papillomatosis, hairy cell leukemia. It is used in heroic situations, eg retinitis in HIV+ve treatment. Drug of choice for Hep C (Ifn alpha 2A) used in combination with ribavarin (ribavarin causes teratogenic effects in females, depression, anemias); however it does not work for all 6 genotypes of Hep C. PEGSA= Ifn bound to polyethylene glycol (sugar) to prevent Ifn inactivation by the liver.
Side effects of In treatment: severe fatigue with high doses, fevers, alopecia, bone marrow effects (anemia). |
|
|
Term
|
Definition
| produced in leukocytes. It is NOT glycosylated. There are 20 different subtypes, genes found on chromosome 9. |
|
|
Term
|
Definition
produced by fibroblasts. It is glycosylated.
Gamma Ifn: produced by activated T cells. Only one gene on chromosome 12. Glycosylated |
|
|
Term
|
Definition
found in trophoblast cells. About 5 genes involved in its synthesis.
Receptors for type 1 Interferon is coded for by a gene on chromosome 21. Some people have 3 chromosome 21,and their cells are very sensitive to Ifn.
Receptor for type 2 Ifn is found on chromosome 6. |
|
|
Term
1st line of infection (after the skin): the virus must defeat the Ifn producing capability of the cell it comes into contact with. Infection is aborted if the virus enters a cell that produces Ifn for neighboring cells.
Type 2 Ifn heat stable, inactivated at pH 2
Gamma Ifn: produced by activated T cells. Only one gene on chromosome 12. Glycosylated
Receptor for type 2 Ifn is found on chromosome 6. |
|
Definition
|
|
Term
| what are the antiviral effects of IFNs are exerted through several pathways; |
|
Definition
1) Increased expression of Class I and Class II MHC ( glycoproteins, thereby facilitating the recognition of viral antigens by the immune system.
(2) Immunoregulatory effects - activation of cells with the ability to destroy virus-infected targets; these include NK cells and macrophages. IFNs appear to drive a shift from humoral to cellular immunity.
(3) Direct inhibition of viral replication: several mechanisms contribute to the third pathway.
production of specific inhibitory proteins eg. the Mx protein which has specific anti-influenza action. It is likely that more specific inhibitory proteins will be identified.
inhibition of viral processes such as penetration, uncoating and budding from infected cells have been reported.
in vitro studies with extracts of IFN-treated cells show that the main target of IFN action is translation, which is blocked by 2 mechanisms, both requiring the presence of minute amounts of dsRNA;-
(i). activation of a dsRNA dependent protein kinase - this phosphorylates and inactivates the translation initiation factor eIF-2. The phosphorylation freezes the initiation complex formed by eIF-2, GTP and met-tRNAf with the small ribosomal subunit and mRNA. Because eIF-2 cannot be recycled, protein synthesis is inhibited or stopped.
(ii). activation of 2-5 oligo A synthetases ® synthesis of 2-5A ® activates endonuclease L (itself induced by IFN) ® degradation of mRNA ® inhibition of protein synthesis.
The combination of cell growth inhibition and enhancement of CMI (cell mediated immunity) accounts for the antitumour effect of IFN. |
|
|
