interferon-alpha (ifn-α) is secreted from which cells course hero

by Garnett Little 6 min read

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What is the difference between interferon α and IFN-β?

Overall, IFN-α can be used to treat hepatitis B and C infections, while IFN-β can be used to treat multiple sclerosis. Interferon type II ( IFN-γ in humans): This is also known as immune interferon and is activated by Interleukin-12. Type II interferons are also released by cytotoxic T cells and type-1 T helper cells.

What is the composition of interferon alpha?

Composition. Interferon alpha contains a mixture of several proteins, all with structural, serological, and functional properties typical for natural interferon alpha (IFN α). The major subtypes identified are IFN-α1, IFN-α2, IFN-α8, IFN-α10, IFN-α14 and IFN-α21. Of these, IFN-α2 and IFN-α14 are glycosylated.

What is the function of human type I interferons?

Human type I interferons ( IFNs) are a large subgroup of interferon proteins that help regulate the activity of the immune system. Interferons bind to interferon receptors. All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor ( IFNAR) that consists of IFNAR1...

What is the International Nonproprietary Name for Interferon alpha?

Although the pharmaceutical product is often simply called "interferon alpha" or "IFN-α" like its endogenous counterpart, the product's International nonproprietary name (INN) is interferon alfa (the spelling of 'alfa' with 'f' reflects INN naming conventions).

Where are interferons secreted from?

Interferons are secreted by infected cells to warn their neighbors, and once stimulated, cells of the immune system secrete interferons as part of their viral surveillance. Interferons are small proteins that bind to receptors on the cell surface.

What secretes interferon alpha?

IFN-alpha 1 is secreted by immune (lymphocytes, NK cells, B-cells and T-cells, macrophages) and non-immune cells (fibroblasts, endothelial cells, osteoblasts and others) in answer to a viral infection.

Where are interferon alpha produced?

IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens.

What cells secrete interferon alpha and beta?

IFN-β was first isolated from fibroblasts, while IFN-α was discovered in lymphoid cells. Within the IFN-α family alone, there are over 13 subtypes encoded by different genes.

How is IFN secreted?

IFN‐γ is primarily secreted by activated T cells and natural killer (NK) cells, and can promote macrophage activation, mediate antiviral and antibacterial immunity, enhance antigen presentation, orchestrate activation of the innate immune system, coordinate lymphocyte–endothelium interaction, regulate Th1/Th2 balance, ...

Which cells secrete IFN-gamma?

Interferon-gamma is secreted predominantly by activated lymphocytes such as CD4 T helper type 1 (Th1) cells and CD8 cytotoxic T cells (23–26), γδ T cells (27–33), and natural killer (NK) cells (34, 35) and, to a less extent, by natural killer T cells (NKT), B cells (36–39), and professional antigen-presenting cells ( ...

Do B cells produce IFN?

B cells produce IFN-gamma in response to IL-12 and IL-18 and when primed by Th1 cells.

Do epithelial cells produce interferons?

When an epithelial cell or fibroblast is infected by virus, RLRs activate NF-κB and IRF3, which then move into the nucleus and upregulate IFN-β and IFN-λ1 transcription. These ligands are then secreted from the basolateral surface of the cell.

Where are dendritic cells?

Dendritic cells are found in tissue that has contact with the outside environment such as the over the skin (present as Langerhans cells) and in the linings of the nose, lungs, stomach and intestines. Immature forms are also found in the blood.

How is IFN-gamma produced?

IFN-γ is produced predominantly by natural killer cells (NK) and natural killer T cells (NKT) as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops as part of the adaptive immune response.

How long did it take for the interferon gene to be found in different human chromosomes?

They described these observations in a 1959 publication, naming the responsible factor viral inhibitory factor (VIF). It took another fifteen to twenty years, using somatic cell genetics, to show that the interferon action gene and interferon gene reside in different human chromosomes.

What is the role of interferons in the immune system?

In general, type I and II interferons are responsible for regulating and activating the immune response . 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 .

What type of interferon is released by cytotoxic T cells?

Interferon type II ( IFN-γ in humans): This is also known as immune interferon and is activated by Interleukin-12. Type II interferons are also released by cytotoxic T cells and type-1 T helper cells. However, they block the proliferation of type-2 T helper cells. The previous results in an inhibition of T h 2 immune response ...

What are the different types of interferons?

Types of interferon. 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 specific cell surface receptor complex known as the IFN-α/β receptor ( IFNAR) that consists of IFNAR1 and IFNAR2 chains.

How does interferon affect the immune system?

All interferons share several common effects: they are antiviral agents and they modulate functions of the immune system. Administration of Type I IFN has been shown experimentally to inhibit tumor growth in animals, but the beneficial action in human tumors has not been widely documented. A virus-infected cell releases viral particles that can infect nearby cells. However, the infected cell can protect neighboring cells against a potential infection of the virus by releasing interferons. In response to interferon, cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 in response to new viral infections; the phosphorylated eIF-2 forms an inactive complex with another protein, called eIF2B, to reduce protein synthesis within the cell. Another cellular enzyme, RNAse L —also induced by interferon action—destroys RNA within the cells to further reduce protein synthesis of both viral and host genes. Inhibited protein synthesis impairs both virus replication and infected host cells. In addition, interferons induce production of hundreds of other proteins—known collectively as interferon-stimulated genes (ISGs)—that have roles in combating viruses and other actions produced by interferon. They also limit viral spread by increasing p53 activity, which kills virus-infected cells by promoting apoptosis. The effect of IFN on p53 is also linked to its protective role against certain cancers.

How do viruses inhibit IFN?

Viruses that inhibit IFN signaling include Japanese Encephalitis Virus (JEV), dengue type 2 virus (DEN-2), SARS-CoV-2 and viruses of the herpesvirus family, such as human cytomegalovirus (HCMV) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8). Viral proteins proven to affect IFN signaling include EBV nuclear antigen 1 (EBNA1) and EBV nuclear antigen 2 (EBNA-2) from Epstein-Barr virus, the large T antigen of Polyomavirus, the E7 protein of Human papillomavirus (HPV), and the B18R protein of vaccinia virus. Reducing IFN-α activity may prevent signaling via STAT1, STAT2, or IRF9 (as with JEV infection) or through the JAK-STAT pathway (as with DEN-2 infection). Several poxviruses encode soluble IFN receptor homologs—like the B18R protein of the vaccinia virus—that bind to and prevent IFN interacting with its cellular receptor, impeding communication between this cytokine and its target cells. Some viruses can encode proteins that bind to double-stranded RNA (dsRNA) to prevent the activity of RNA-dependent protein kinases; this is the mechanism reovirus adopts using its sigma 3 (σ3) protein, and vaccinia virus employs using the gene product of its E3L gene, p25. The ability of interferon to induce protein production from interferon stimulated genes (ISGs) can also be affected. Production of protein kinase R, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral activities of interferons by gene (and thus protein) mutation. The H5N1 influenza virus, also known as bird flu, has resistance to interferon and other anti-viral cytokines that is attributed to a single amino acid change in its Non-Structural Protein 1 (NS1), although the precise mechanism of how this confers immunity is unclear.

What is the IFN?

Interferon type I (α/β/δ...) Interferons ( IFN s, / ˌɪntərˈfɪərɒn /) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral ...

Which cells secrete IFN-?

IFN-α and IFN-β are secreted by many cell types including lymphocytes ( NK cells, B-cells and T-cells ), macrophages, fibroblasts, endothelial cells, osteoblasts and others. They stimulate both macrophages and NK cells to elicit an anti-viral response, involving IRF3/IRF7 antiviral pathways, and are also active against tumors. Plasmacytoid dendritic cells have been identified as being the most potent producers of type I IFNs in response to antigen, and have thus been coined natural IFN producing cells.

Which type of cells produce IFN?

Plasmacytoid dendritic cells have been identified as being the most potent producers of type I IFNs in response to antigen, and have thus been coined natural IFN producing cells. IFN-ω is released by leukocytes at the site of viral infection or tumors.

What is recombinant interferon omega?

Recombinant feline interferon omega is a form of cat IFN-α (not ω) for veterinary use.

What is the purpose of IFNs?

1wu3 I:22-182. Human type I interferons ( IFNs) are a large subgroup of interferon proteins that help regulate the activity of the immune system. Interferons bind to interferon receptors.

How does IFN- affect fever?

IFN-α acts as a pyrogenic factor by altering the activity of thermosensitive neurons in the hypothalamus thus causing fever. It does this by binding to opioid receptors and eliciting the release of prostaglandin-E 2 (PGE 2 ).

Is IFN a pseudogene?

This subtype of type I IFN was recently described as a pseudogene in human, but potentially functional in the domestic cat genome. In all other genomes of non-feline placental mammals, IFN-ν is a pseudogene; in some species, the pseudogene is well preserved, while in others, it is badly mutilated or is undetectable.

Is interferon negative regulation?

In both mice and human, negative regulation of type I interferon is known to be important. Few endogenous regulators have been found to elicit this important regulatory function, such as SOCS1 and Aryl Hydrocarbon Receptor Interacting Protein (AIP).

How many amino acids are in an interferon?

All the interferons are proteins. The human alpha interferons (IFN-α) are proteins having 165 or 166 amino acids as they are produced by the cells.

What is the mechanism of action of interferons?

The mechanism of action of interferons is interesting in the sense that the interferons produced by host cells in response to viral attack have no direct effect on the viruses, rather they induce an antiviral state in neighbours healthy host cells that prevents viral replication in such cells (Fig. 11.15). Double-stranded RNA viruses are the most potent inducers of interferon synthesis.

What are the two types of interferons?

The interferons represent proteins with antiviral activity that are secreted from cells in response to a variety of stimuli. There are two types of interferons (Table 11.2), Type I and Type II, and interferon-like cytokines. Type I interferons consist of seven classes—IFN-α, IFN-β, IFN-ԑ, IFN-κ, IFN-ω, IFN-δ, and IFN-τ. Type II interferon consists of IFN-ϒ only.

Why is interferon considered a nonspecific resistance factor?

Interferon appears to be body’s first line of defense against viral infection and is considered as nonspecific resistance factor because it does not exhibit specificity towards a particular virus.

Which bacteria were introduced to the interferon gene?

But, at last, the technique of genetic engineering came to forefront and the genetic engineers successfully integrated interferon gene into a plasmid and introduced it into E. coli and Methylophilus methylotrophus bacteria.

What are the four interferon-like cytokines?

Four interferon-like cytokines have been reported: limitin (found only in mice), IL-28A, IL-28B, and IL-29 found in human and other mammals. IFN-α, IFN-β, IFN-ԑ, IFN-κ, IFN-ω. IL-28A, IL-28B, and IL-29 are found in humans, whereas IFN-δ, IFN-τ, and limitin are not. IFN-τ was described first as ovine trophoblast protein-1 and is found in ungulates where it is required for implantation of the ovum, but there is no direct human homologue.

What is the material that is secreted into the medium after a virus infection?

They named this material interferon.

Types of Interferon

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Based on the type of receptorthrough which they signal, human interferons have been classified into three major types. 1. Interferon type I: All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α/β receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. The type I interferons present in humans …
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Function

  • All interferons share several common effects: they are antiviral agents and they modulate functions of the immune system. Administration of Type I IFN has been shown experimentally to inhibit tumor growth in animals, but the beneficial action in human tumors has not been widely documented. A virus-infected cell releases viral particles that can infect nearby cells. However, t…
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Induction of Interferons

  • Production of interferons occurs mainly in response to microbes, such as viruses and bacteria, and their products. Binding of molecules uniquely found in microbes—viral glycoproteins, viral RNA, bacterial endotoxin (lipopolysaccharide), bacterial flagella, CpG motifs—by pattern recognition receptors, such as membrane bound toll like receptors or the cytoplasmic receptors …
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Downstream Signaling

  • By interacting with their specific receptors, IFNs activate signal transducer and activator of transcription (STAT) complexes; STATs are a family of transcription factorsthat regulate the expression of certain immune system genes. Some STATs are activated by both type I and type II IFNs. However each IFN type can also activate unique STATs. STAT activation initiates the mos…
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Virus Resistance to Interferons

  • 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), den…
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Coronavirus Response

  • Coronaviruses evade innate immunity during the first ten days of viral infection. In the early stages of infection, SARS-CoV-2 induces an even lower interferon type I (IFN-I) response than SARS-CoV, which itself is a weak IFN-I inducer in human cells. SARS-CoV-2 limits the IFN-III response as well. Reduced numbers of plasmacytoid dendritic cells with age is associated with increased COVID-…
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Interferon Therapy

  • Diseases
    Interferon beta-1a and interferon beta-1b are used to treat and control multiple sclerosis, an autoimmune disorder. This treatment may help in reducing attacks in relapsing-remitting multiple sclerosisand slowing disease progression and activity in secondary progressive multiple scleros…
  • Drug formulations
    Several different types of interferons are approved for use in humans. One was first approved for medical use in 1986. For example, in January 2001, the Food and Drug Administration (FDA) approved the use of PEGylated interferon-alpha in the USA; in this formulation, PEGylated interfe…
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History

  • Interferons were first described in 1957 by Alick Isaacs and Jean Lindenmann at the National Institute for Medical Research in London; the discovery was a result of their studies of viral interference. Viral interference refers to the inhibition of virus growth caused by previous exposure of cells to an active or a heat-inactivated virus. Isaacs and Lindenmann were working …
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