Interferon gamma (IFN-γ) is a signaling molecule within the immune system, classified as a type II interferon. It is a soluble cytokine, acting as a messenger between immune cells. IFN-γ is produced primarily by specialized immune cells such as T lymphocytes (CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T cells) and natural killer (NK) cells. This cytokine regulates immune cell communication and influences their activity.
Orchestrating Immune Responses
IFN-γ orchestrates both innate and adaptive immune responses. It activates macrophages, enhancing their ability to engulf and destroy pathogens. This activation leads to changes within macrophages, including the production of reactive oxygen species (ROS) and nitric oxide (NO), which help kill microbes inside cells.
IFN-γ also enhances antigen presentation by upregulating the expression of major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APCs), such as macrophages and dendritic cells. Improved antigen presentation allows T cells to recognize and respond more effectively to foreign invaders. Additionally, IFN-γ promotes the differentiation of naive T cells into Th1 cells, creating a positive feedback loop as Th1 cells are major producers of IFN-γ, further amplifying the immune response.
Defending Against Invaders and Abnormal Cells
IFN-γ directly contributes to the body’s defense against pathogens and cancerous cells. It exhibits direct antiviral properties by interfering with viral replication. For example, in herpes simplex virus I (HSV) infections, IFN-γ can inhibit the virus’s ability to replicate by compromising its transport mechanisms.
Beyond its direct effects, IFN-γ activates immune cells to target and eliminate infected or tumor cells. It promotes the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), which are specialized in identifying and destroying compromised cells. IFN-γ also activates macrophages, equipping them with enhanced antimicrobial activity and the ability to destroy infected cells. In the context of cancer, IFN-γ helps activate macrophages towards a pro-inflammatory and tumoricidal (M1-like) phenotype, making them more effective at killing tumor cells.
Balancing Inflammation and Autoimmune Conditions
IFN-γ has a complex role in inflammation, capable of both promoting and regulating immune responses. It induces the expression of proteins that promote inflammatory responses.
However, dysregulation of IFN-γ production or signaling can contribute to autoimmune disorders. In conditions like inflammatory bowel disease and diabetes, aberrant IFN-γ production has been observed. Chronic exposure to IFN-γ can also lead to immune evasion, where tumor cells upregulate inhibitory molecules like programmed-death ligand 1 (PD-L1) to avoid immune attack. This highlights the delicate balance required for IFN-γ to function beneficially without excessive inflammation or tissue damage.
Medical Applications and Future Directions
The understanding of IFN-γ’s functions has led to its use in medical diagnostics and therapeutics. One diagnostic application is the Interferon-Gamma Release Assay (IGRA), used for tuberculosis testing. This test measures IFN-γ released by T cells when exposed to specific tuberculosis antigens, indicating a prior infection. This provides a more specific diagnostic tool compared to older methods.
Therapeutically, IFN-γ has been utilized in treating certain diseases. For example, it is approved for use in chronic granulomatous disease (CGD), a genetic disorder that impairs the immune system’s ability to fight off bacterial and fungal infections. IFN-γ administration in CGD patients enhances phagocytic cell function, improving their ability to clear infections. Ongoing research explores further possibilities for modulating IFN-γ activity, either by enhancing its effects in cancer or by inhibiting its activity in autoimmune diseases.