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Cytokines. Cytokines and their Receptors in Inter-Cellular Communication. Cytokines-Based Diseases and Cytokine Therapy. Updated: November 15, 2012. Folder title: Cytokine. (Presented in Part 2 under “Cells of the Immune Response”). Key Hematopoietic Growth Factors and Their Targets.
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Cytokines Cytokines and their Receptors in Inter-Cellular Communication Cytokines-Based Diseases and Cytokine Therapy Updated: November 15, 2012 Folder title: Cytokine
(Presented in Part 2 under “Cells of the Immune Response”) 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
Cytokine Table P l eo t r o pic R e d u n d a n t
Activities of Cytokines: What They Do Cytokines in Hematopoiesis Cytokines in Innate and Adaptive immunity
Hematopoiesis Stem Cell Factor from Bone Marrow Stromal Cells Lymphocytes Hematopoietic Cytokines and Hematopoiesis: Immunology, 5th Edition, Figure 12-16, p. 297 ------------------Myelocytes------------------
Stem Cell Production Myelocyte Production Lymphocyte Production
The Complexity of Cytokine-Receptor Signaling and Effects What cytokine is being made? When is it being made? At what concentration? How long will it be around? Is it being modified by other proteins? Activated? Degraded? What other cytokines are being made? Do they affect the first cytokine? Do they activate or inhibit the first cytokine? Is the cytokine receptor available on the target cell or cells? Is the receptor being activated or inhibited? Is the receptor defective? Does the receptor have a high enough affinity for the cytokine?
Cytokines: Where They Come From: The Discovery of IL1 How They Work
Discovery of IL1 PHA = phytohemagglutinin (poly-clonal t-cell mitogen from fungi
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
Cytokines and TH1 and TH2 Helper T-Cell Subsets: Immunological and Pathobiological Effects
Blocked TH1 and TH2 in Disease Blocked
Dashed -------- arrow indicates blocking response Roles of TH1 and TH2
Cytokines and TH1 and TH2 See Table 12-4, p. 315, Top Half Immunology, 6th Edition
Functions of TH1 and TH2 See Table 4-4, p. 96 for structures and functions of IgG subtypes See Table 12-4, Bottom Half, p315, 6th Edition
TH1 and TH2 Helper Cell Subsets in the Pathology and Progression of Infection with Mycobacterium lepraeTuberculoid (Cell-mediated) and Lepromatous (Humoral response) Leprosy(Figure 12-14, Immunology, 6th Edition, p. 318)M-RNA from Tuberculoid or lepromatous lesions analyzed for types of cytokines being produced
Cytokine Receptors in Normal immune Response and in Pathobiology 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.
Receptors for IL2 Gamma subunit is used by other cytokine receptors (IL15, IL7, IL9, IL4)
General model of cytokine receptors for interleukin and interferon types of cytokines. See figure 12-6 (b) and (c) p. 308, for interleukin (“hematopoietin”) and interferon class of cytokines STAT = signal transducers and activators of transcription. See Table 12-2, p. 313 for STAT family of transcription factors associated with different cytokines of the interleukin and interferon series
IL2 Receptor Family Figure 12-7 (c) Kuby, 6th Ed., p. 309 IL2RFam
Cytokines, Cytokine Receptors, and Human Disease(Part 1): Over-production of Cytokines 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
Cytokines, Cytokine Receptors, and Human Disease(Part 2) Cytokine Receptor Miss-expression Cutaneous T-Cell Lymphoma Inappropriate Expression of IL-2 and IL-2R 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
Cytokines, Cytokine Receptors, and Human Disease(Part 3) Cytokine Receptor Blocking Chagas Disease (Trypanosoma Cruzi) Severe Immunosuppression of Infectious Etiology Blocked Expression of IL-2R Alpha Subunit
Cytokines, Cytokine Receptors, and Human Disease (Part 4)Cytokine Mimics Anti-inflammatory and Immunosuppressive Viral Products as Mimics of Cytokinesand Cytokine Receptors XSCID
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 Macrophage inflammatory protein For information on chemokines, See Table 13-2, p. 330, and footnotes to Table 13-2, Kuby, 6th Edition. Chemokines are small MW cytokines that mostly regulate leukocyte trafficking and adherence but also regulate non-leukocyte cellular interactions. Monocyte chemoattractant protein
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 ImmediateHypersensitivity: 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?
Turning Down Helper T-Cell and Cytotoxic T-Cell Mediated Auto-immune Responses
Cytokine Activation of Leucocytes in Anti-Leukemia Treatments
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