Interferons immune response

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Cellular cytokines (interferons, G-CSF) and immune response modifiers originally produced from human cells, most often leukocytes, have now been replaced with recombinant products with well-defined structure/function. Futuristic advances in experimental hematology portend development of human blood cells produced from the hemopoetic stem cells. Yet for the foreseeable future, homologous blood donated by healthy, altruistic voluntary blood donors remains the principal source of safe and adequate supply of blood and blood products for transfusion therapy. 

Immune Defense. Figure 2 Cytokines involved in the development of adaptive immune responses in secondary lympoid tissues such as the lymph nodes or spleen. Abbreviations B B-lymphocyte, IFN interferon, Ig immunoglobulin, IL interleukin, NK natural killer cell, TE T-effector (cytotoxic) lymphocyte, TH T-helper lymphocyte... 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

Gough DJ, Sabapathy K, Ko EY, Arthur HA, Schreiber RD, Trapani JA, Clarke CJ, Johnstone RW (2007) A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon gamma response genes. J Biol Chem 282 938-946 Guidotti LG, Chisari EV (2001) Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19 65-91... 

Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T (2005) IRF-7 is the master reguiator of type-I interferon-dependent immune responses. Nature 434 772-777... 

Innate immune response to viral infections is predominately through interferon-alpha, -beta (IFN-a and -P) induction and activation of natural killer (NK) cells. Although viral replication can induce IFN-a and -P expression, macrophages are capable of producing and secreting cytokines which also induce the production of these type I interferons (Falk 2001). Bound IFNa and p to its receptors on NK cells increases its ability to lyse virally-infected cells. 

A recent report has demonstrated that the proteolytic activity of NS3 plays an additional role in viral infection, beyond polyprotein processing. An important mediator of the cellular immune response is the transcription factor interferon regulatory factor 3 (IRF-3), which becomes activated on infection and then stimulates production of type-1 interferon and other antiviral genes [46]. It was found that expression of heterodimeric NS3/4A... 

DNA viruses modulate the host immune response, e.g., most likely the etiologic agent of Kaposfs sarcoma, KSHV (human herpes vims —8), has captured complement-binding proteins, three cytokines (two macrophage inflammatory proteins and interleukin 6), bcl-2, interferon regulatory factors, interleukin 8 receptor. Certain retroviruses... 

Biomedical research continues to broaden our understanding of the molecular mechanisms underlining both health and disease. Research undertaken since the 1950s has pinpointed a host of proteins produced naturally in the body that have obvious therapeutic applications. Examples include the interferons and interleukins (which regulate the immune response), growth factors, such as erythropoietin (EPO which stimulates red blood cell production), and neurotrophic factors (which regulate the development and maintenance of neural tissue). 

Colonna, M., Krug, A., and Celia, M. 2002. Interferon-producing cells on the front line in immune responses against pathogens. Current Opinion in Immunology 14(3), 373-379. 

ISG15 (UCRP) Statl, others Immune response (interferon)... 

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. 

Cytokines such as interferons are used for the treatment of hepatitis, cancer, and lymphoma interleukins are used to enhance immune response and growth factors are used for the treatment of anemia and regulation of tumor angiogenesis. 

Interferons—Family of immune system signal proteins that interfere with the ability of viruses to infect cells. Interferons have been genetically engineered to provide treatments by weakening immune response in autoimmune disease such as multiple sclerosis, or by strengthening immune response in diseases like hepatitis C. 

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