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CYTOKINES- ITS PROPERTIES AND FUNCTION

CYTOKINES- ITS PROPERTIES AND FUNCTION. BY- CHANDANA KALITA MSC BIOTECHNOLOGY 2 nd SEM ROLL NO. 03 GAUHATI UNIVERSITY. CYTOKINES.

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CYTOKINES- ITS PROPERTIES AND FUNCTION

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  1. CYTOKINES- ITS PROPERTIES AND FUNCTION BY- CHANDANA KALITA MSC BIOTECHNOLOGY 2nd SEM ROLL NO. 03 GAUHATI UNIVERSITY

  2. CYTOKINES • Cytokines are low molecular weight regulatory proteins or glycoproteins secreted by specific cells of the immune system and various other cells in the body in response to a number of stimuli. • Role: Assist in the induction and regulation of the cellular interactions involving cells of the immune system, inflammatory and hematopoietic systems. • Importance: Category of signaling molecules that are used extensively in cellular communication.

  3. CYTOKINES • Cytokines were initially discovered as soluble substances- thought to be secreted by mainly activated T-cells. • Were initially called lymphokines, the term coined by Dumonde in 1969. • Later it was discovered that many of such lymphokines are also produced by nonimmunological cells which play an important role in immunological processes- named CYTOKINES.

  4. GENERAL PROPERTIES OF CYTOKINES • Peptides or glycopeptides –molecular mass ranging between 15 -25 KD • Can exist as monomer(IL-2,GM-CSF), dimers(IFN-gamma,IL-8,MCSF,TNF-betta) or trimers(TNF- alpha) • Stable to temperature and PH than enzymes and can be stored at 0-4oC for months • Withstand exposure to 56oC upto 1 hour • Their isoelectric points vary between 2.5-10.5

  5. PROPERTIES • Bind receptors, alter gene expression. • Specific membrane receptors determine the succeptibility of the target cell to a particular cytokine. • High affinity between cytokines and their receptors- mediate biological effects at picomolar concentration.

  6. PROPERTIES • Potent -some function at 10-15 Molar • Local -Autocrine -Paracrine -(Sometimes) endocrine • Highly interactive -pleiotropic (single cytokine having different effect on different cells) -redundant (different cytokines having same function) -synergistic /antagonistic

  7. PROPERTIES

  8. PROPERTIES

  9. PROPERTIES

  10. PROPERTIES

  11. PROPERTIES • Cytokines can activate many cells eg. cytokines secreted by TH cells can affect B-cells, CTLs, macrophages, natural killer cells- CASCADE INDUCTION Cytokines regulate the immune response

  12. SITE OF CYTOKINE SYNTHESIS • Most lymphoid tissues such as spleen, lymph nodes, blood leukocytes are capable of producing cytokines. • Thymus and bone marrow are not efficient in this regard. • T-cells are major producers,B-cells are also capable.

  13. CYTOKINE FAMILIES • Hematopoietic family • Interferon family • Tumour necrosis factor family • Chemokine family 1,2 & 3 elicit physiolgical responses 4 serves as a chemoattractant

  14. Macrophage Neutrophil B-Cell Eosinophil Basophil T-Cell Mast Cell IFNaIFNb IFNg IL-1IL-6 IL-10 IL-12 IL-15 TNFa IL-1IL-8TNFa IL-10IL-12TNFaTNFb IL-1IFNaIFNbTNFaTNFb IL-1 IFNaIL-6 IFNgIL-8 IFNaIL-10IL-12IL-15IL-18 TNFa IL-1IL-8 IL-1 IFNaIL-3 IFNb IL-4 IFNgIL-10 TNFaIL-13 TNFb IL-5 IL-1 IFNa IL-6 IFNbIL-10 TNFaIL-12 TNFb TNFa IL-1 IFNa IL-2 IFNbIL-4 IFNgIL-6IL-10IL-13IL-14 IL-1 IFNgIL-3 TNFa IL-4 TNFb IL-8 IL-4 IL-1IL-3IL-4IL-8 IL-4 IL-2 IL-16IL-4 IL-17 IL-6 IFNa IL-8 IFNbIL-9 IFNg IL-4 IL-3IL-9IL-10 IL-3IL-4IL-5 IL-10 IL-4 IL-10 IL-4IL-5 c 2009 ProteinLounge.com

  15. Table 1  -  FEATURES OF CYTOKINES

  16. Cross-Regulation of Cytokines • CD4+ T-helper cells can be divided into subsets based on their cytokine production • Th-1 cells produce IL-2, IFN-gamma, TNF-bettaCKs which activate cell-mediated immunity • T h-2 cells activate IL-4, IL-6, IL-10 CKs which activate humoral activity

  17. Cross Regulation of Cytokines • First, cytokines promote the growth of the subset that produces them. • Second, they inhibit the development and activity of the opposite subset, this effect is known as cross-regulation eg. IFN-gamma(secreted by TH1) inhibits proliferation of the TH2 subset. Again, IL-4 and IL-10 (secreted by TH2) down regulate the secretion of IL-12, which is critical cytokine for TH1 differentiation

  18. FACTORS AFFECTING CYTOKINE PRODUCTION • Act as messengers between the cells and the brain to alert the body to certain disturbances • Factors which may elicit cytokine production include illnesses and conditions that the immune systemwill need to fight off • Infections, either bacterial or viral, can both increase cytokine production dramatically

  19. FACTORS AFFECTING CYTOKINE PRODUCTION • White blood cells release cytokines into the bloodstream to alert the body so more T-cells can be produced and released to fight off the infection • The additional proteins in the blood are what cause the spike in temperature associated with infection • Certain cancers and other conditions may also cause a spike in immune response within the body

  20. Factors affecting cytokine production • Those with arthritis and other autoimmune conditions often have higher than normal levels of cytokine production because their immune systems begin responding and attacking the body itself.

  21. GENERAL ROLE OF CYTOKINES • Development of cellular and humoral immune responses • Induction of the inflammatory response • Regulation of hematopoiesis • Control of cellular proliferation and differentiation and • Healing of wounds

  22. Therapeutic Uses of Cytokines 1) Interferon in treatment of viral diseases, cancer 2) Several cytokines are used to enhance T-cell activation in immunofideficincy diseases, e.g. IL-2, IFN-,TNF- 3) IL-2 and lymphokine activating killer cells (LAK) in treatment of cancer 4) GM-CSF induces increase in white cell count, it is used: a- To restore leukocytic count after cytotoxic chemotherapy induced neutropenia b- After bon marrow transplantation c- To correct AIDS-associated leukopenia

  23. Therapeutic Uses of Cytokines 5) Anti-cytokines antibodies in management of autoimmune diseases and transplant rejection: a- Anti-TNF in treatment rheumatoid arthritis b- Anti-IL2R to reduce graft rejection 6) Anti-TNF antibodies in treating septic shock 7) Anti-IL-2R  in treating adult T-cell leukemia 8) Anti-IL-4 is under trial for treatment of allergies

  24. THANK YOU

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