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Cytokines

Cytokines. Ahmad Shihada Silmi Hematologist & Immunologist IUG. General Characteristics. Mediate and regulate the immune system Secretion is brief and self-limited Individual cytokines are produced by multiple cell types Act of multiple cell types-pleiotrophic

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Cytokines

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  1. Cytokines Ahmad Shihada Silmi Hematologist & Immunologist IUG

  2. General Characteristics • Mediate and regulate the immune system • Secretion is brief and self-limited • Individual cytokines are produced by multiple cell types • Act of multiple cell types-pleiotrophic • (PLEITROPISM): one type of cytokine may act on several different cell types.

  3. General Characteristics Actions are redundant • (REDUNDANCY): different cytokines may have the same effect.

  4. General Characteristics • Effect synthesis and actions of other cytokines. • (SYNERGY): two or more different cytokines may have a greater than additive effect. • (ANTAGONISM): one type of cytokine may the action of another type of cytokine.

  5. Cells That Make Cytokines And Their Function • A Variety Of Cells Are Capable Of Making Cytokines • However The Biggest Producers: M and TH • Cytokines Are Involved In • Hematopoiesis • Adaptive Immunity • Innate Immunity • Inflammation • Activities Established Thru Recombinant Cytokines (Simplistic Approach), In Vivo Function Can Vary

  6. General Functions1- Mediators of natural/innate immunity • Produced mainly by mononuclear phagocytes in response to infectious agents. • Act on endothelial cells ( production of adhesion molecules for B-cells and T-cells to bind to and or leukocyte activation ); main members of this group are: • TNF ( tumor necrosis factor): • Causes endothelial cells to produce adhesion molecules for lymphocytes and secret chemokines ( guide leukocytes to the site of inflammation “chemotaxis “ ). • Causes fever. B. IL-7: similar / same effect as TNF. C. IL-6 D. IL-8 E. INF-γ: causes activation of macrophage.

  7. General FunctionII- MEDIATORS & REGULATORS OFADAPTIVE IMMUNITY • Produced mainly by T-lymphocytes in response to specific regulation of antigen. • Act on lymphocyte to induce growth & differentiation during the activation phase at T-cell dependent immune response. • Also act on EFFECTOR CELLS (such as mononuclear phagocytes, neutrophil and eosinophils) in the effector phase of adaptive immune response. • These are divided into:

  8. A- ACTIVATORS OF CYTOTOXIC RESPONSE: • Induction of macrophage cytotoxic T cell & NK cell activation. • Main members of the group: • IL-2:causes exponential proliferation of T cells after recognition of antigen • IL-3 • INF-γ: similar effect to IL-2 • LT ( lymphotoxin): similar effect to TNF, thus as a link between T-cell activation & inflammation.

  9. B- ACTIVATORS OF HUMORAL RESPONSE: • Induction of B-cell activation • Main members of the group: • IL-2: is produced by T-cells, thus have similar gene effect on B-cells • IL-3 • IL-4: similar/ same effect as IL-2, and also cause isotype switch to IgE. • IL-5: causes isotype switch to IgA • IL-6: causes B-cells differentation to plasma cells • TGF-B (Transforming Growth Factor- β): causes isotype switch towards IgA • INF-γ: cause isotype switch towards IgG

  10. General Function III- Activators of inflammatory cells • Type II IFN • IFN-g

  11. General Functions VI- Stimulators of hematopoiesis • Produced by BONE MARROW STROMA CELL & leukocyte to stimulate growth & differentation of immature leukocytes. • Main members of the group. A. IL-3: causes induction of all principal hematocytes. B. IL-7: induction of B- and T- lymphocytes. C. CSF (STEM CELL FACTOR ) :induction of all principal hematocytes. D. GM-CSF (granulocyte –monocytes –CSF. E. M-CSF (MONOCYTE-CSF ). F. G-CSF (GRANULOCYTES-CSF ).

  12. Cytokines Are Non-Specific • How Does Immune Specificity Fit With Non-Specific Cytokines • Answer 1: Thru Receptors • Receptors Expressed On Antigen Activated Cells • Answer 2: Close Proximity To Cytokine Secreting Cells. • Ex. APC-TH • Cytokine Concentrations (TH) Are High Locally • Only Interacting APC Gets Activated • Answer 3: Short Half Life • Short ½ Life Ensures Local Activity

  13. Cytokine Receptors • 5 Major Families • Immunoglobulin Superfamily • Hematopoietin Receptor Family (Class I) • Interferon Receptor Family (Class II) • TNF Receptor Family • Chemokine Receptor Family • Class I and II (Majority Of Receptors) • Multimeric • Upon Receptor Engagement, Tyrosine Phosphorylation

  14. Hematopoietin Receptor Family (Class I)

  15. Th17 (CD4+, FoxP3-) IL-17 is a pro-inflammatory cytokine Promotes secretion of pro-inflammatory cytokines (IL-6) from fibroblasts, epithelial and endothelial cells. Th17 cells are critical to anti-bacterial immunity. Over expression of IL-17 is associated with rheumatoid arthritis, SLE, MS and asthma Treg (CD4+, Foxp3+) Natural (develop in the thymus) Prevent effector T cell development in LN Induced (develop in the periphery) Develop under the influence of TGF-ß Inhibit effector T cell function in periphery. Th17 and Treg Cells

  16. Regulation of Cytokines • Chromatin Structure (Regulation of expression)

  17. Cytokine Therapies Suppression of TH-cell poliferation and TC-cell activation

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