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Cytokines Cytokines-Based Diseases and Cytokine Therapy Cytokines and their Receptors in Inter-Cellular Communication Updated: November 28, 2011 Folder.

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Presentation on theme: "Cytokines Cytokines-Based Diseases and Cytokine Therapy Cytokines and their Receptors in Inter-Cellular Communication Updated: November 28, 2011 Folder."— Presentation transcript:

1 Cytokines Cytokines-Based Diseases and Cytokine Therapy Cytokines and their Receptors in Inter-Cellular Communication Updated: November 28, 2011 Folder title: Cytokine

2 Key Hematopoietic Growth Factors and Their Targets Relatively Multi-Specific: Granulocyte-Macrophage Colony-Stimulating Factor GMCSF Interleukin III - IL3 Relatively Mono-Specific: Granulocyte Colony Stimulating Factor - GCSF Macrophage Colony Stimulating Factor - MCSF Erythropoietin - EPO GrowFact

3 Cytokine Table

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5 Macrophage to T-Helper

6 Inter-Leukins and IL-Receptors

7 Interleukin Actions

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9 Pleiotropic activity of Interferon Gamma. Immunology, 5 th Edition, Figure 15-15, p. 355 Gamma Interferon

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11 Table of Redundancy and Pleiotropy See Table 15-3, Immunology, 5 th Edition, p. 350

12 TH1 and TH2 in Disease Blocked

13 Roles of TH1 and TH2

14 Cytokines and TH1 and TH2 See Table 12-4, p. 315, Immunology, 6 th Edition

15 Functions of TH1 and TH2

16 TH1 and TH2 Helper Cell Subsets in the Pathology and Progression of Infection with Mycobacterium leprae Tuberculoid (Cell-mediated) and Lepromatous (Humoral response) Leprosy (Figure 12-14, Immunology, 6 th Edition, p. 318) Leprosy

17 Discovery of IL1

18 In this graphic, PHA (phytohemagglutinin) is a non-specific mitogen that stimulates T-cell proliferation measured by labeled thymidine incorporation into the cell culture. Why use PHA? Why not use a specific T-cell antigen? 0 of 94 Response Grid

19 The Specific Cytokines that are present, and their concentrations matter in how the immune response reacts. The presence and structure of cytokines receptors matter just as much as the cytokines themselves.

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22 IL2 Receptor Family IL2RFam Figure 12-7 (c) Kuby, 6th Ed., p. 309

23 Cytokines, Cytokine Receptors, and Human Disease (Part 1) Bacterial Septic Shock: Bacterial Cell-wall Endotoxins Macrophage Overproduction if IL-1 and TNF-alpha Bacterial Toxic Shock Polyclonal activation of T-cells by Super-Antigens Over-production of IL-1, TNF, other cytokines Cutaneous T-Cell Lymphoma Inappropriate Expression of IL-2 and IL-2R Chagas Disease Blocked Expression of IL-2R Alpha Subunit CytoSick

24 Cytokines, Cytokine Receptors, and Human Disease (Part 2) X-Linked Severe Combined Immune-Deficiency (X-SCID) Boy-in-the Bubble Syndrome Failure to Express IL-2R Gamma Subunit May Also Affect IL4R and IL7R Produces Broad-ranging Immune Unresponsiveness Anti-inflammatory and Immunosuppressive Viral Products as Mimics of Cytokines and Cytokine Receptors XSCID

25 Gamma C Subunit Shared

26 Severe Combined Immune Deficiency or “Boy-in-a-bubble Syndrome” arises because of 1.A congenital abnormality affecting cytokine synthesis 2.A severe viral infection 3.A congenital abnormality affecting the coding of cytokine receptor subunit 4.A metabolic defect that generates an inhibitor of a cytokine receptor 5.A bacterial endotoxin 6.An autoimmune antibody attack 0 of 94 Response Grid

27 Viral Mimics of Cytokines and Receptors Immunosuppression and Anti-inflammatory Effects of Viral Mimics of Cytokines and of Cytokine Receptors. (Kuby, 6th Ed., p. 314) Viral Mimics For information on chemokines, See Table 13-2, p. 330, and footnotes to Table 13-2, Kuby, 6 th Edition. Not part of BIO 447 Exams or Quizzes.

28 (This is a fill-in-the-blank question) Several viruses are known to produce soluble interferon-γ receptors (INFγR). Why would producing a soluble INFγR be something the virus “wants” to do? Why does that help the virus? (You can use INF to abbreviate interferon-γ) __________________________________ 0 of 103

29 Other Sources of Cytokines used in Host Response to Pathogens: e.g. Mediators in Type I Immediate Hypersensitivity

30 Overview of Mast Cell Mediated Type I Immediate Hypersensitivity: Triggering of Sensitized Cells and Release of Early and Late Mediators: How Do We Treat This??? IgEOView

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32 Cytokines in Therapy of Diseases Since cytokines have potent activities at low concentrations in controlling responses of host cells to normal and pathological events, can we use Cytokines deliberately in therapy?

33 Tumor Necrosis Factor and Melanocytes

34 Tumor Necrosis Factor in Vivo

35 Tumor Necrosis Factor and Weight Loss

36 Cytokine Therapies in the Clinic

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39 LAK Cells

40 TIL Cells

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42 On a scale of -2 to +2 rate: 1 = -2 = I’m totally lost; 2 = -1 = I’m having a hard time but I get some of it 3 = 0 = I’m doing OK. I get a lot of it. I’ll figure the rest out later 4 = +1 = I’m doing fine. I get most of it; 5 = +2 = This is no problem. Please get moving before I get totally bored

43 I am here! n 0 of 103 1.Yes 2.No 3.Not sure

44 Hematopoietic Cytokines and Hematopoiesis: Immunology, 5 th Edition, Figure 12-16, p. 297 He mat opoi esis

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46 IL1, Tumor Necrosis Factor (TNFά) and IL6 all promote fever responses These three cytokines are ___________________ in this effect. 1.Antagonistic 2.Pleiotropic 3.Redundant 4.Synergistic 5.Independent 6.Mutually exclusive 0 of 103 Response Grid

47 IL4 and IL10 inhibit activation of Th1 cells and enhance activation of Th2 cells. Interferon Gamma inhibits the activation of Th2 cells and stimulates the activation of Th1 cells. That means that IL4 and IL10 on the one hand and Interferon gamma on the other hand are ___________________. 1.Antagonistic 2.Pleiotropic 3.Redundant 4.Synergistic 5.Independent 6.Mutually exclusive 0 of 94 Response Grid


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