Interferons Immune System – Immune Regulation, Antiviral Defense and Biomarker Analysis
What is the interferons immune system?
The Interferons immune system plays a central role in host defense against viral infections, tumors, and immune dysregulation. Interferons (IFNs) are cytokines that act as key signaling molecules coordinating innate and adaptive immune responses.
Interferons are classified into three main types based on their receptors and biological functions:
Type I interferons (IFN-α, IFN-β)
Type II interferon (IFN-γ)
Type III interferons (IFN-λ)
Each interferon type activates distinct yet interconnected signaling pathways that regulate antiviral immunity, inflammation, immune cell activation, and immune surveillance.
Dysregulation of interferon signaling is associated with chronic viral infections, autoimmune diseases, cancer progression, and impaired immune responses
AMPK substrates act in specific subcellular locales to rewire metabolism.
Overview of interferon signaling pathways in vertebrate hosts. Production of interferons (IFNs) begins with the binding of viral molecules, such as genomic nucleic acids, to either cell surface or intracellular pattern recognition receptors (PRRs) [18,19]. The resulting signaling cascade activates transcription and secretion of IFNs, which then bind to their associated IFN receptor on the same and nearby cells. Binding of IFNs to their receptors activates a signal cascade by Janus tyrosine kinases (JAK) and tyrosine kinase (TYK) that leads to the phosphorylation of STAT1 and/or STAT2 [9,15]. For type I and III IFNs, STAT1 and STAT2 complex with IRF9 and bind to IFN-stimulated response elements (ISREs) to express IFN-stimulated genes (ISGs). For type II IFNs, phosphorylated STAT1 dimers bind to gamma-activated site (GAS) elements for ISG production [9,15]. In turn, ISGs mediate antiviral effects directly within infected cells, or further induce innate and adaptive immune responses [3,120].
Key takeaways
Central regulators of antiviral and antitumor immunity
Bridge innate and adaptive immune responses
Act through JAK-STAT signaling pathways
Control expression of interferon-stimulated genes (ISGs)
Highly relevant for immune profiling and biomarker discovery
Types of interferons and their immune functions
Type I interferons (IFN-α / IFN-β)
Type I interferons are rapidly produced by infected cells in response to viral nucleic acids detected by pattern recognition receptors (PRRs). They induce a strong antiviral state by activating hundreds of interferon-stimulated genes (ISGs) that inhibit viral replication and spread.
Type II interferon (IFN-γ)
IFN-γ is primarily produced by NK cells and T lymphocytes. It plays a critical role in immune activation, macrophage polarization, antigen presentation, and antitumor immunity.
Type III interferons (IFN-λ)
Type III interferons mainly act at epithelial barriers, such as the respiratory and gastrointestinal tracts. They provide antiviral protection with limited systemic inflammation.
Interferon signaling mechanisms
Interferon signaling is initiated when viral or microbial components bind to cell-surface or intracellularPRRs, triggering interferon production.
Secreted interferons bind to their specific receptors on the same or neighboring cells, activating Janus kinases (JAKs) and TYK2, which phosphorylate STAT1 and STAT2.
Type I and III IFNs form STAT1-STAT2-IRF9 complexes that bind to interferon-stimulated response elements (ISREs).
Type II IFN activates STAT1 homodimers that bind to gamma-activated sequences (GAS).
This leads to transcription of interferon-stimulated genes (ISGs), which execute antiviral, immunomodulatory, and inflammatory functions.
Biological roles of interferons in the immune system
Antiviral defense: Interferons induce ISGs that block viral entry, replication, and assembly, protecting infected and neighboring cells.
Immune modulation: They regulate activation and differentiation of NK cells, T cells, dendritic cells, and macrophages.
Antigen presentation: Interferons increase expression of MHC class I and II molecules, enhancing immune recognition of infected or malignant cells.
Inflammation control: While promoting immune activation, interferons also contribute to immune regulation to prevent excessive tissue damage.
Interferons in cancer and immune-mediated diseases
Interferons play a dual role in cancer biology and immune-mediated disorders.
Cancer and immunotherapy
Type I interferons enhance tumor antigen presentation and T-cell–mediated immunity. IFN-α has been used clinically in melanoma and hematological malignancies to boost antitumor responses.
Autoimmune and inflammatory diseases
Persistent interferon signaling contributes to autoimmune conditions such as systemic lupus erythematosus and multiple sclerosis.
Viral and respiratory infections
Interferon responses are critical in controlling respiratory viral infections, including influenza and SARS-CoV-2.
Therapeutic and clinical applications of interferons
Interferons are used clinically in several contexts:
Viral infections: hepatitis B and C
Autoimmune diseases: IFN-β in multiple sclerosis
Cancer therapy: immune activation and tumor control
Understanding interferon-driven gene expression signatures is essential for therapeutic stratification and response monitoring.
Why study interferons immune system with AnyGenes?
At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® designed to analyze interferon signaling and immune responses.
By measuring expression of interferons, receptors, and ISGs using targeted gene expression approaches such as qPCR arrays.
He Y, et al. Suppression of Interferon Response and Antiviral Strategies of Bunyaviruses. Trop Med Infect Dis. (2024)7;9(9):205.
Liu YG, et al. Interferon lambda in respiratory viral infection: immunomodulatory functions and antiviral effects in epithelium. Front Immunol. (2024)1:15:1338096.
Schoggins JW. Interferon-Stimulated Genes: What Do They All Do? Annu Rev Virol. (2019)29;6(1):567-584.
Lee AJ, Ashkar AA. The Dual Nature of Type I and Type II Interferons. Front Immunol. (2018)11;9:2061.