Cytokines Cytokines and their Receptors in Inter-Cellular Communication Cytokines-Based Diseases and Cytokine Therapy Updated: November 28, 2011 Folder title: Cytokine 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 Cytokine Table Macrophage to T-Helper Inter-Leukins and IL-Receptors Interleukin Actions Gamma Interferon Pleiotropic activity of Interferon Gamma. Immunology, 5th Edition, Figure 15-15, p. 355 Table of Redundancy and Pleiotropy See Table 15-3, Immunology, 5th Edition, p. 350 Blocked TH1 and TH2 in Disease Blocked Roles of TH1 and TH2 Cytokines and TH1 and TH2 See Table 12-4, p. 315, Immunology, 6th Edition Functions of TH1 and TH2 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, 6th Edition, p. 318) Leprosy Discovery of IL1 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? Response Grid 0 of 94 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. IL2 Receptor Family Figure 12-7 (c) Kuby, 6th Ed., p. 309 IL2RFam 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 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 Gamma C Subunit Shared Severe Combined Immune Deficiency or “Boy-in-a-bubble Syndrome” arises because of 1. 2. 3. 4. 5. 6. A congenital abnormality affecting cytokine synthesis A severe viral infection A congenital abnormality affecting the coding of cytokine receptor subunit A metabolic defect that generates an inhibitor of a cytokine receptor A bacterial endotoxin An autoimmune antibody attack Response Grid 0 of 94 Immunosuppression and Anti-inflammatory Effects of Viral Mimics of Cytokines and of Cytokine Receptors. (Kuby, 6th Ed., p. 314) Viral Mimics of Cytokines and Receptors For information on chemokines, See Table 13-2, p. 330, and footnotes to Table 13-2, Kuby, 6th Edition. Not part of BIO 447 Exams or Quizzes. Viral Mimics (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 Other Sources of Cytokines used in Host Response to Pathogens: e.g. Mediators in Type I Immediate Hypersensitivity 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 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? Tumor Necrosis Factor and Melanocytes Tumor Necrosis Factor in Vivo Tumor Necrosis Factor and Weight Loss Cytokine Therapies in the Clinic LAK Cells TIL Cells 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 2 1 0 -1 -2 Duration: 0 Seconds n 33% N su re ot N 0 of 103 33% o 33% Y 1. Yes 2. No 3. Not sure es I am here! mat opoi esis Hematopoietic Cytokines and Hematopoiesis: Immunology, 5th Edition, Figure 12-16, p. 297 IL1, Tumor Necrosis Factor (TNFά) and IL6 all promote fever responses These three cytokines are ___________________ in this effect. Antagonistic Pleiotropic Redundant Synergistic Independent Mutually exclusive 0 of 103 an Sy ed un d 0% 0% 0% Response Grid ne rg is t ic In de pe M nd ut ua en t lly ex cl us iv e 0% t ic 0% tr op Pl ei o A nt a go ni st ic 0% R 1. 2. 3. 4. 5. 6. 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. 2. 3. 4. 5. 6. Antagonistic Pleiotropic Redundant Synergistic Independent Mutually exclusive Response Grid 0 of 94