Download Interferons

By uzair hashmi
Introduction
Types
Function
Induction of Interferon (IFN’s)
Downstream Signaling
Virus resistance to interferon
Diseases
Interferon (IFN’s) are proteins made and released by
eukaryotic cells in the presence of pathogens- such
as viruses, bacteria or parasites- or tumor cells.
 They allow communication between cells to trigger
the protective defenses of the immune system that
eradicate pathogens or tumors.
 They are not expressed in normal cells but viral
infection of a normal cell causes interferon to be
made and released from the cell.

They are a part of non-specific immune system and
are induced at an early stage in viral infectionbefore the specific immune system has had time to
respond.
 IFN’s belong to a large class of Glycoprotein known
as Cytokines.
 Interferon are named after their ability to ‘interfere’
with viral replication within host cells.
 About ten distinct IFN’s have been identified in
mammals, seven of these have been described for
humans.

Based on the type of receptor through which
they signal, human interferon have been
classified into three major types;

Type l

Type ll

Type lll
Type l interferon have two further sub-types:

Interferon-alpha or Leukocyte interferon, which is
produced by virus infected leukocytes. They are a
family of about twenty related proteins.

Interferon-beta or Fibroblast interferon, produced
by virus infected fibroblasts. They are particularly
potent as anti-viral agents.

All type l IFNs bind to a specific cell
surface receptor complex known as the
IFN-alpha receptor (IFNAR) that
consists of IFNAR1 and IFN AR2.

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Interferon Type ll or interferon-gamma,
which is also known as immune interferon, is
produced by certain activated T-cells and NK
cells.
Interferon-gamma is made in response to
antigen (including viral antigens) or mitogen
stimulation of lymphocytes.
It binds to IFNGR.

Acceptance of this classification is less
universal than that of type l and Type ll.

Unlike the other two, it is not currently
included in Medical Subject Headings.

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All interferon share several common effects, they are
anti-viral agents and can fight tumors.
Another function of Interferon is to up regulate major
histocompatibility complex molecules MHC l and
MHC ll, and increase immunoproteasome activity.
Higher MHC 1 expression increases presentation of viral
peptides to cytotoxic T-cells, while the
immunoproteasome processes viral peptides for
loading onto the MHC l molecule, thereby increasing
the recognition and killing of infected cells by T-cells.
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As an infected cell dies from a cytolytic virus,
viral parasites are released that can infect
nearby cells.
However, the infected cell can warn
neighboring cells of a viral presence by
releasing interferon.
The neighboring cells, in response to
interferon, produce large amounts of an
enzyme known as protein kinase R (PKR).
Membrane bound toll like receptors
or the cytoplasmic receptors RIG1
or MDA5, can trigger release of
IFNs.
 Toll Like Receptor 3 (TLR3) is
important for inducing interferon in
response to the presence of double
stranded RNA viruses, the ligand
for this receptor is double stranded
RNA (dsRNA).
 After binding dsRNA, this receptor
activates the transcription factors
IRF3 and NF-kB, which are
important for initiating synthesis of
many inflammatory proteins.

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By interacting with their specific receptors,
IFNs activate signal transducer and activators
of transcription (STAT) complexes.
STATs are a family of transcription factors,
that regulate the expression of certain
immune system genes.
Some STATs are activated by both type l and
type ll IFNs. However, each type can also
activate unique STATs.
Many viruses have evolved mechanisms to resist
interferon activity.
 They circumvent the IFN response by blocking
downstream signaling events that occur after the
cytokine binds to its receptor by preventing further
IFN production, and by inhibiting the functions of
proteins that are induced by IFN.
 Viruses that inhibit IFN signaling include Japanese
Encephalitis Virus (JEV), dengue type 2 virus (DEN-2),
and viruses of the herpes virus family such as Human
cytomegalovirus and Kaposi's sarcoma associated
herpes virus (KSHV).
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The immune effects of interferon may help
for diseases such as actinic keratosis,
superficial basal cell carcinoma, pappiloma
and external genital warts.
Synthetic IFNs are also made, and
administered as anti-viral, antiseptic and anti
carcinogenic drugs, and to treat some
autoimmune diseases.