Interferons Flashcards
3 distinct classes of interferon
- IFN-α
- IFN-β
- IFN-γ
Interferon
A substance secreted by virally infected cells that mediate resistance
Functions of interferons
- Induction of cellular resistance to viral attack
- Regulation of immune function
- Regulation of growth and differentiation of many cell types
- Sustenancce of early phases of pregnancy in some animal species
Type I interferons
- Acid-stable
IFN-α & IFN-β
- 30% amino aicd identity
- bind to same receptor
- induce similar activities
Type II interferon
IFN-γ
- evolutionarily distinct from other interferons
- binds to separate receptor
- induces different range of activity
Biological effects of type I interferons
Antiviral activity
Anti-proliferative effect
Anti-tumour effects of type I interferons
Have ability to increase NK and T-cytotoxic cell acitivity
Biological effects of type II interferons
Weak antiviral and anti-proliferative activity.
Represents main macrophage-activating factor
IFN-γ
Macrophage-mediated effects
- Destruction of invading microbes
- Destruction of intracellular pathogens
- Tumour toxicity
- Increased MHC antigen expression leading to enhanced activation of lymphocytes via antigen presentation
IFN-γ
What happens when IFN-γ is co-administered with type I interferons
Potentiates the antiviral and anti-proliferation activities of IFN-α & IFN-β
Initial therapeutic application of interferons
- Identified in late 1950s but therapeutic application rendered impractical due to low levels produced by the body.
- Large scale purification from sources like blood was non viable.
- Interferons exhibit species preference - only human derived interferons can be used in human medicine
First production of interferon in small quantities
- Until 1970s
- Sourced from human leukocytes obtained from transfused blood supplies
- only 1% pure
- contained mixture of various IFN-αs
First production of interferon in large quantities
- late 1970s
- mammalian cell culture
- cancer cell lines were found to secrete greater quantities of interferons and were amenable to large scale culture due to their transformed nature
Namalaw cell line
A specific strain of human lymphoblastoid cells
- the major industrial source of interferon
Interferon production from namalwa cell line
- Cells propagated in animal cell fermenters
- The additon of an inducing virus (sendai virus)
- Results in production of leukocyte interferon.
- Final product contained 9 IFN-α subtypes
Tradename given to one of first approved interferon products
Wellferon
Most interferons currently in medical use
Recombinant human products produced by E. coli