Type II interferon

IFN-y modulates a number of components of the immune response. This is the only type II IFN whereas there are more than 20 types of type I IFNs (IFN-a, IFN-(3, IFN-w and IFN-t). It is not related to type I IFNs, has separate receptors and is encoded by a different chromosomal locus. IFN-y is produced by activated T lymphocytes (THi and CD8+ cells), NK cells, B cells, NKT cells and professional APCs. It promotes the activity of cytolytic T lymphocytes, macrophages and NK cells. The cell self-activation and activation of nearby cells in part may result from IFN-y production by professional APCs, which include monocyte/macrophage and dendritic cells. The early host defense against infection is likely to utilize IFN-y secreted by NK and professional APCs. In acquired immune responses, T lymphocytes are the major source of IFN-y. 

IFN-y production is regulated by IL-12 and IL-18, both cytokines secreted by APCs. In the innate immune response, a link is established between infection and IFN-y by these cytokines. IL-12 and chemokines including macrophage inflammatory protein-la (MIP-la) are secreted as macrophages recognize pathogens, and NK cells are attracted to the site of inflammation by the chemokines. This is followed by the induction of IFN-y production and secretion by IL-12. IL-12 and IL-18 further stimulate the production of IFN-y from macrophages. The production of IFN-y is inhibited by IL-4, IL-10 and TGF-(3. 

IL-1 (IL-lot and -( ) Macrophages, dendritic cells, endothelial cells, other cells TH and B cells and various other tissues Activation (other details provided in the text) 

IL-2 THi cells TH, Tc and NK cells T cell and NK proliferation and induction of activity 

IL-3 THi and TH2 cells, mast cells, NK cells Hematopoietic and mast cells Progenitor cell proliferation and differentiation 

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Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5 375— 386... 

Type II interferons. These are acid-labile and are also known as immune (IFN-y) interferons because they are produced by T-lymphocytes (see Chapter 14) in the eellular immune system in response to specific anhgens. 

IFN-y is evolutionarily distinct from the other interferons it binds to a separate receptor and induces a different range of biological activities. It is thus often referred to as type II interferon. 

Interferon-7 was the first secretory product of T cells to be discovered when it was found that supernatants derived from suspensions of T cells that had been treated with mitogenic agents could activate macrophages. This macrophage activating factor , subsequently found to interfere with the replication of viruses, was thus named interferon. The production of this compound, associated with delayed-type hypersensitivity and cell-mediated immunity, was termed immune interferon or type II interferon. With the discovery of other lymphokines with interferon-like activity (interferon-a and -j3), the compound was finally designated interferon-7. 

Type II interferon. Type I interferon binds to receptor, which in turn activates tyrosine kinase phosphorylation and the subsequent transcription pathway that induces viral resistance. Similarly, Type II interferon binds to another receptor and activates the immune response. 

IFN-a and -jS display significant amino acid sequence homology (30%), bind to the same receptor, induce similar biological activities and are acid-stable. For these reasons, IFN-a and IFN-)S are sometimes collectively referred to as type I interferons , or acid-stable interferons . IFN-y is evolutionarily distinct from the other interferons it binds to a separate receptor and induces a different range of biological activities, and it is thus often referred to as type II interferon. 

Types I and type II Interferon Signaling IFNa/p IFNy... 

Specific agents are synthesized using recombinant DNA or other biosynthetic techniques to mimic the effects of naturally-occurring type I or type II interferons. 

Several Type I and Type II interferons (IFN) and interleukin-2 (IL-2) have been approved to treat infectious diseases or malignancies by augmenting immune responses IFN-a2a (chronic hepatitis C) IFN-a2b (hepatitis C, melanoma, chronic myelogenous leukemia, hairy-cell leukemia, Kaposi s sarcoma, cutaneous T-cell lymphoma, renal cell carcinoma) IFN-aconl (chronic hepatitis C) IFN- 31a (multiple sclerosis) IFN-pib (multiple sclerosis) IFN-ylb (malignant osteopetrosis) and IL-2 (renal cell carcinoma). 

Among the most highly selective cytokine biopharmaceuticals are the interferons. Interferons are members of a large family of related proteins that may be divided into two categories type I and type II interferons. Type I interferons (i.e., a- and P-interferon) possess antiviral and anti-proliferative properties, whereas type II interferons (i.e., y-interferon) have immunostimulatory activity. Several animal species were examined for their responsiveness to interferons, and with the exception of nonhuman primates, all tested animal species were found to be unresponsive [15]. 

Bazan, J. F. (1990a). Shared architecture of hormone binding in type I and type II interferon receptors. Cell6, 753-754. 

Marchetti M, Monier MN, Fradagrada A, Mitchell K, Bayche- 126. tier F, Bid P, Johannes L, Lamaze C. Stat-mediated signaling induced by type I and type II interferons (IFNs) is differentially controlled through lipid microdomain association and clathrin-dependent endocytosis of IFN receptors. Mol. Biol. Cell 2006 17 2896-2909. 

Interferons There are two types of interferons Type I, which includes IFN-a and IFN- 3 and Type II consisting of IFN-y. IFN-a and (3 have about 30% homology in amino acid sequence. There are two more recently discovered Type I interferons they are called IFN-cu and IFN-x. IFN-a and IFN- 3 each have 166 amino acids, and IFN-y has 143. Both IFN-a and IFN- 3 are of single chain structure and bind to the same type of cell surface receptors, whereas IFN-y is a dimer of two identical chains and interacts with another type of receptors. All our cells can produce Type I interferons when infected by viruses, bacteria and fungi. Flowever, only T cells and natural killer cells can produce Type II interferon. Type I interferon binds to receptor, which in turn activates tyrosine kinase phosphorylation and the subsequent transcription pathway that induces viral resistance. Similarly, Type II interferon binds to another receptor and activates the immune response. 

IFN-P shares 29% amino acid homology with IFN-a and has been used in the treatment of multiple sclerosis. Type 1 interferons (a and P) differ from Type II interferons (y) in biochemical properties, biological function, and receptor specificity. Side effects common to both classes of interferons include chills, fever, rigors, headache, myalgia s, hypotension, nausea, vomiting, anorexia, constipation, fatigue, neutropenia, and elevated transaminases. This constellation of symptoms frequently results in mild to moderate hypotension and volume depletion and could potentially contribute to prerenal azotemia or acute tubular necrosis. 

Hovanessian, A. G., Meurs, E., Aujean, O., Vaquero, C., Stefanos, S. and Falcoff, E., 1980, Antiviral response and induction of specific proteins in cells treated with immune (Type II) interferon analogous to that from viral interferon (Type I)-treated cells. Virology 104 195. 

GRAYFER L, GARCIA EG, BELOSEVIC M (2010), Comparison of macrophage antimicrobial responses induced by type II interferons of the goldfish Carassius auratus L.) , I Biol Chem, 285,23537-47. 

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