NAJRAN UNIVERSITY College of Medicine NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 17 Microbiology &Immunology Course Lecture No. 17 By Dr. Ahmed Morad Asaad Associate Professor of Microbiology Dr. Ahmed Morad Asaad Associate Professor of Microbiology

CYTOKINES They include: ‑ lymphokines (secreted by lymphocytes). ‑ Monokines (secreted by macrophages). ‑ Interleukins and interferon ‑ They are low molecular weight soluble proteins. ‑ They regulate the amplitude and duration of the immune inflammatory responses. ‑ They contribute to the control of haemopoiesis, macrophage activation, chronic inflammation and growth and differentiation of T and B cells during the acquired immune response.

Cytokines include the following : (1)Interferons (IFNs). (2)Interleukins (ILs). (3) Colony stimulating factors (CSFs). (4) Others as tumour necrosis factors  and  (TNF ‑  and  ) and transforming growth factor  (TGF ‑  ).

interferons (IFNs) - IFNs are a large family of proteins secreted by most cells of vertebrates in response to viral infections, or other selected stimuli. There are 3 types : IFN  produced by leucocytes. IFN  produced by fibroblasts. Both are induced by viral infections IFN  is also called immune interferon and is produced by T ‑ cells when stimulated by specific antigen or mitogen. ‑ Actions of interferons: 1. Antiviral activity : Interferons were first recognized by their ability to interfere with viral infection in cultured cells,

- They are produced soon (less than 48 hours) after viral infection, in contrast to antibodies, which appear several days after infection. Hence, IFNs may act in early phase of viral diseases to limit the spread of virus. - Interferons inhibit intracellular replication of viruses in neighboring cells by inducing proteins that prevent the translation of viral mRNA, i.e. they block viral protein synthesis. - Interferon activity is not specific, i.e. an interferon induced by one virus can inhibit replication of any other virus. However, they are species specific, i.e. an interferon produced in mice will only be active in mice.

- Due to this property and the fact that induced cells synthesize quite small amounts of interferon, production of interferon has been difficult. - However, with recombinant DNA techniques, it is possible now to produce human interferon by cloning interferon genes and their expression in large amounts in bacteria and yeast.

2. Immunomodulatory action by  interferon, which includes: 1- It stimulates differentiation of T c cells. 2- It stimulates IgG 2 secretion by B ‑ cells. 3- It is a macrophage activating factor. 4- It enhances cytotoxic actions of NK cells. 5- It antagonizes several actions of IL ‑ 4.

3. Antiproliferative actions : 1- IFNs inhibit cell proliferation and tumor growth. 2- For this action and for their immunostimulatory effects on macrophages, NK cells, etc…, they are used in cancer therapy.

Interleukins: There are more than 16 types. The most important are shown in: InterleukinSourceEffects IL-1Macrophage1- Activates TH cells. 2- B-cell growth and antibody production. 2- Acute phase response. 3- Macrophage activation. 4- Promotes hematopoiesis. IL-2Th cells1- Activation of both T helper and T cytotoxic cells. 2- Activation of NK. 3- B cell proliferation and lg production

ILSourceEffects IL-3T lymphocytes  Growth and differentiation of bone marrow stem cells. IL-4 & IL-5 T helper and mast cells  B cell proliferation.  lgE production by IL-4.  Stimulate TH2 cell,  TC proliferation and functions.  Eosinophil and mast cell growth and function.  Inhibit monokine production. IL-6T helper cells, macrophages  Synergetic effects with IL-1 or TNF  Acute phase response and fever  B cell growth and function

Therapeutic Uses of Cytokines 1 ‑ IL ‑ 2 and LAK cells are used in adaptive immunotherapy of tumors. 2 ‑ IL ‑ 2 is used in treatment of AIDS through activation of NK cells. 3 ‑ TNF  and IL2 are used in cancer therapy. Also TNF  causes hemorrhagic necrosis of tumors. 4 ‑ CSF may be of value in: Treatment of leucopenia after chemotherapy, radiation therapy or AIDS ‑ associated leucopenia. In bone marrow transplantation. May help to protect against bacterial septicemia.

5 ‑ Interferons have proven most useful in : a)Treating hematological disorders. b)Both IFN  and IFN  have been effective in treatment of patients with chronic active hepatitis B and C infections. c)Trials of IFNs in treatment of AIDS are promising. d)Interferon treatment may be helpful in certain severe viral infections (rabies, hemorrhagic fever, herpes encephalitis). f)Topical interferon in the eye may suppress herpetic keratitis.