Structure of Cytokine Receptors PDF

Structure of cytokine receptors 2 Structure of cytokine receptors  Groups of cytokine receptors share identical or highly homologous subunit chains 3 Signaling through...

Structure of cytokine receptors 2 Structure of cytokine receptors  Groups of cytokine receptors share identical or highly homologous subunit chains 3 Signaling through the TNF receptor 4 JAK-STAT signaling induced by cytokines  Cytokine receptors of the type I and type II receptor families engage signal transduction pathways that involve non- receptor tyrosine kinases called Janus kinases (JAKs) and transcription factors called signal transducers and activators of transcription (STATs).  Small molecule JAK antagonists have been approved for the treatment of acute myeloid leukemia, and chronic inflammatory diseases, including rheumatoid arthritis and psoriasis.  T cell proliferation, triggered by cytokines such as IL-2, is targeted by some immunosuppressive small molecules. Rapamycin (mTOR inhibitor) 5 Changes in surface molecules after T cell activation 6 Regulation of IL-2 receptor expression Structure of IL-2 and its receptor 7 Biologic actions of IL-2  Autocrine  Paracrine  Endocrine 8 9 10 Interferon Interferon is also called interferon alfa or Intron A. Interferon is used for several different types of cancer including:  kidney cancer (renal cell cancer)  melanoma  multiple myeloma  some types of leukaemia You are more likely to have interferon as an injection just under the skin (subcutaneously). Or you might have it into the bloodstream through a drip (infusion). How often you have it depends on which type of cancer you are having treatment for. Most people have interferon 3 times a week. Or you might have it as a daily injection. https://www.cancerresearchuk.org/immunotherapy/types/cytokines 12 Interleukin 2 Aldesleukin Aldesleukin is also called Interleukin 2, IL2 or Proleukin. In cancer care, IL-2 is most often used to treat kidney cancer. It is also in clinical trials for some other types of cancer. You are most likely to have it as an injection just under the skin (subcutaneously). But you may have it into a vein, either as an injection or through a drip. How often you have this drug depends on which cancer you are being treated for. The side effects of interferon and aldesleukin include:  a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness  flu-like symptoms  diarrhea  tiredness and weakness (fatigue)  feeling sick  loss of appetite Aldesleukin can also cause low blood pressure. 13 https://www.cancerresearchuk.org/immunotherapy/types/cytokines Role of T cells in eradicating infections  CD4+ T cells recognize antigens of phagocytosed and extracellular microbes and produce cytokines that recruit and activate the phagocytes to kill the microbes.  CD8+ T cells can also secrete some cytokines and participate in similar reactions. B, CD8+ cytotoxic T lymphocytes (CTLs) recognize antigens of microbes residing in the cytoplasm of infected cells and kill the cells. 15 Steps in CD4+ T cell-mediated immune responses 16 Subsets of CD4+ Effector T Cells CXCR3 / CCR5 P, E Selectins Tissues of innate Immunity CCR3-4-8 Mucosal Tissues CCR6 Tissues cells, Macrophages Th1/Th2 Germinal centers 17 Development of Subsets of CD4+ Effector T Cells Th1 Cells Th2 Cells Th17 Cells 18 Functions of Th1 cells  IFN-γ activates macrophages to kill phagocytosed microbes.  FN-γ promotes the differentiation of CD4+ T cells to the Th1 subset and inhibits the development of Th2 and Th17 cells.  IFN-γ stimulates expression of several different proteins that contribute to enhanced antigen presentation and T cell activation  IFN-γ acts on B cells to promote switching to certain IgG subclasses, and to inhibit switching to IL- 4–dependent isotypes, such as IgE.  Th1 cells produce tumor necrosis factor (TNF) and various chemokines, which contribute to the recruitment of leukocytes and enhanced inflammation.  Th1 cells are also produce IL-10, which functions mainly to inhibit dendritic cells and macrophages and thus to suppress Th1 activation. 19 Macrophage activation by Th1 cells 20 Functions of Th2 Cells 23 Classical and alternative macrophage activation 24 Functions of Th17 Cells 25  Induction and effector phases of CD8+ T cell responses 26 Role of helper T cells in the differentiation of CD8+ T lymphocytes 27 Inhibition of CD8+ T Cell Responses: T Cell Exhaustion Steps in CTL-mediated lysis of target cells 28 Mechanisms of CTL-mediated killing of target cells 30