1 / 45

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

onan
Download Presentation

Cytokines

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related