INTERFERONS

INTERFERONS
INTERFERONS are proteins belonging to class of cytokines .although, they have the ability to protect against both bacteria, viruses, parasites and tumour. ;they are mainly known for their antiviral functions.

Different animals produce different interferons; and different cells of a given species also produce different interferons. Due to this, interferons show antiviral activity not only against viruses but also against cells of different species like that of mice or chickens.

TYPES OF INTERFERONS
Based on the type of receptor through which they signal, human interferons have been classified into three major types.

Interferon type I:
All type I IFNs bind to a cell surface receptor complex known as the IFN-α/β receptor (IFNAR) that consists of IFNAR1 and IFNAR2 Chains. In general, type I interferons are produced when the body recognizes a virus has attacked it. However, the production of type I IFN-α is prohibited by Interleukin-10. Once released, type I interferons will activate molecules which prevent the virus from producing and replicating its DNA & RNA.

Interferon type II (IFN-γ in humans):
 it's production is activated by Interleukin-12 and it is released by Type 1 T helper cells. However, they block the proliferation of Type 2 T helper cells. IFN type II binds to IFNGR, which consists of IFNGR1 and IFNGR2 chains and has a different receptor than type I IFN.

Interferon type III:
Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12)

NOTE-: Expression of type I and III IFNs can be induced in virtually all cell types upon recognition of viral components, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells.

DOWNSTREAM SIGNALLING :
By interacting with their specific receptors, IFNs activate (STAT) complexes; different interferons can activate same or different STAT.
STAT activation initiates the  (JAK-STAT) signaling pathway.

 IN this pathway, IFN binds to IFN receptors outside cell  and JAKs associate with IFN receptors in cytoplasm and, STAT1 &STAT2 gets activated. As a result, an IFN-stimulated gene factor 3 (ISGF3) complex forms—this contains STAT1, STAT2 and a third transcription factor called IRF9—and moves into the cell nucleus. Inside the nucleus, the ISGF3 complex binds to specific nucleotide sequences called IFN-stimulated response elements (ISREs) in the promoters of certain genes, known as IFN stimulated genes ISGs. This induces transcription of these genes and interferons are produced.

HUMAN INTERFERONS:
They are of 3 types; alpha-interferons , beta-interferons,  gamma-interferons.
They are produced by lymphocytes, other leukocytes  and fibroblasts in connective tissue
Interferons are small proteins with a mol.wt of 15000 to 30000.they are stable at low pH and fairly resistant to heat.

FUNCTIOND OF DIFFERENT INTERFERONS

GAMMA-INTERFERONS -it triggers phagocytosis by macrophages and neutrophils. It is produced by lymphocytes.

ALPHA & BETA-INTERFERON-they are produced by host cells infected by a virus which then diffuse to uninfected neighbouring cells and protect them from viruses and so they are said to be HOST CELL SPECIFIC and not VIRAL CELL SPECIFIC.; Because they cant act against the already infected cell...

MODE OF ACTION OF ALPHA AND BETA INTERFERONS
Virus infect the cells and start replicating there their replication induces host cell to produce mRNA for alpha and beta interferons and their further translation in to alpha and beta interferons proteins. These proteins diffuse to the neighbouring cells and degrade the viruses which infect them.

PROBLEMS WITH INTERFERONS :
They are unstable and effective for short periods. So they play prominent riles in acute and short-term viral infections like cold and influenza. But are quite  ineffective against chronic and long term