IFNપ

IFNપ is a pleiotropic cytokines that plays a central role in promoting innate and adaptive mechanisms of host defense. Among the important sources of IFNy are natural killer (NK) cells,  TH1-type CD4+ and CD8+ T cells. NK cells and CD8+ T cells rapidly produce IFNy following primary activation, hwereas CD4+ T cells undergo a period of development that dtermines whether type I or II cytokines are produced.

IFNપ  exerts is biologic effects by intereacting with an IFNપ  receptor that is ubiquitously expressed on nearly all cells. Functionally active IFNપ  receptors consist of a 90-kDa receptor α chain and a 62 kDa receptor β chain. Most if not all, IFNપ  responses in cells result from the ligand-induced coupling of the activation IFNપ  receptor complex to particular components of the JAK-STAT signaling pathway which requires the protein tyrosine kinases Jak1 and Jak2 and the transcription factor Stat1.

IFN-gamma is primarily produced by T and NK cells.

What does IFNપ  do?

IFNપ  is intricately involved in the regulation or development of antiviral T-cell-mediated immune responses. It mediates antiviral activity by inducing apoptosis of cells containing double stranded RNA; increases CD4 T-cell adhesion by upregulating the expression of adhesion molecules.

IFN-y activates macrophages resulting in increased expression of class II MHC molecules, increased cytokine production, and increased microbicidal activity.

Along with IL-2 it results in polyclonal and monoclonal expansion of activated T-cells.

IFNપ selectively inhibits proliferation of Th2 cells.

IFNγ  has an extremely important role in promoting host resistance to infectious organisms. Mice which lack IFNપ  either of the IFNપ  receptor subunits, or any of the 3 proximal JAK-STAT signaling proteins disrupts IFNપ  signaling and results in elimination of innate immunity, rendering the host highly susceptible to infection by a variety of microbial pathogens and certain viruses. Humans who have inactivating mutations in the IFNપ  receptor complex die early in life from uncontrolled mycobacterial infections.

IFNપ  Mice lacking sensitivity to either IFNપ  (i.e., IFNપ  receptor deficient mice) or Stat1-deficient mice develop tumors more rapidly and with greater frequency when challenged with different doses of chemical carcinogens.

IFNγ is usually found elevated in the periopheral blood compartment and in the germainal centers of LN during HIV disease.

How Does IFNપ  Exert Its Effects?

IFNપ  exerts it biologic effect by interacting with an IFNપ  receptor that is ubiquitously expressed on nearly all cells. Functionally active IFNપ  receptors consist of two distinct subunits: a 90-kDa receptor alpha chain (IFNGR1) and a 62-kDa receptor B chain (IFNGR2).

Most IFNપ  responses in cells result from the ligand-induced coupling of the activated IFNપ  receptor complex to particular components of the JAK-STAT signaling pathway. IFNપ  signaling requires 3 specific JAK-STAT pathway components: the protein tyrosine kinases Jak1 and Jak2 and the transcription factor Stat1.

IFNપ  therapy

IFNપ has been used for the therapy of various diseases, including chronic granulomatous diases, malignant diseases, and infectious disease.

Inhibitors of IFNγ

Serotin reportedly blocks LPS's ability to induce IFNγ.