Interferons

Classification of interferons

Based on their ability to bind specific receptors, interferons are grouped into three families:

• Type I. The largest group, including IFNα, IFNβ, IFNδ, IFNε, IFNκ, IFNτ, IFNω, and limitin. Not all variants are present in humans (lacking IFNδ, IFNτ, and limitin). Genes are located on chromosome 9 and lack introns.
• Type II. Represented by a single cytokine — IFNγ (formerly called «immune interferon»). Genetically, structurally, and functionally, it differs significantly from the others.
• Type III. Includes three molecules: IFNλ1, IFNλ2, and IFNλ3 (or IL-29, IL-28A, IL-28B). Genes are located on chromosome 19 and contain introns.

How interferons fight viruses

Direct antiviral action is the hallmark of interferons, especially type I. To suppress viral infection, they trigger intracellular cascades:

1. Degradation of viral RNA. Interferons stimulate the synthesis of 2'5'-oligoadenylate synthetase. It activates the enzyme RNase L, which cleaves single-stranded viral RNA.
2. Cessation of viral protein synthesis. Protein kinase R is induced. Activated by viral double-stranded RNA, it blocks the translation initiation factor eIF2α. As a result, the cell stops assembling viral proteins.
3. Blockade of the viral lifecycle. Interferons trigger the synthesis of Mx family proteins, which are capable of self-assembling into complexes that suppress the transcription of viral proteins.

Producers and receptors

Cells producing interferons depend on the type of molecule. The primary source of type I interferons is plasmacytoid dendritic cells. Upon infection, IFNα begins to be secreted by monocytes, macrophages, and all infected nucleated cells, while IFNβ is secreted predominantly by fibroblasts and epithelium. The main producers of type II interferon (IFNγ) are lymphocytes: natural killer cells (NK cells), T helper 1 cells (Th1), and cytotoxic T lymphocytes.

Interferons act through specific receptors. Type I molecules bind to the IFNAR receptor (composed of β1 and β2 chains). The signal is transmitted inside the cell via Jak family kinases (Jak1, Tyk2) and STAT transcription factors, ultimately triggering the transcription of interferon-stimulated genes.

Immunoregulatory effects

In addition to antiviral activity, interferons modulate immune function. They enhance defense against intracellular bacteria, fungi, and protozoa.

Type I interferons stimulate macrophages, dendritic cells, and cytotoxic lymphocytes, and also upregulate the expression of MHC-I molecules. IFNγ is distinguished by its potent immunoregulatory effect: it strongly activates macrophages, enhances antigen presentation (MHC-II), and directs T-lymphocyte differentiation down the Th1 pathway.

Class and exam questions

What else to study on this topic

• Intracellular signal transduction (JAK-STAT pathway and the role of IRF factors)
• Interaction of interferons with Toll-like receptors (TLRs)
• Kinetics and dynamics of the production of various interferon types
• Interferon-stimulated target genes (MHC, iNOS, TAP)
• Antitumor effects of interferons

Other topics in the "Innate Immunity" section

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