What Schering-Plough Biopharma?

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What Schering-Plough Biopharma?. Pharmaceutical Company What kind of research is performed at the facility?. What Schering-Plough Biopharma?. Pharmaceutical Company What kind of research is performed at the facility? Is there a conflict of interest? - PowerPoint PPT Presentation

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  • What Schering-Plough Biopharma?Pharmaceutical CompanyWhat kind of research is performed at the facility?

  • What Schering-Plough Biopharma?Pharmaceutical CompanyWhat kind of research is performed at the facility?

    Is there a conflict of interest? They all work for Schering-Plough BiopharmaMerged with Merck in 2009

  • What is an Autoimmune disease?Is defined as an immune response against self antigens. What are some of the major autoimmune diseases?

    -Crohns Disease-Lupus -Scleroderma

    - Rheumatoid arthritis - Multiple Sclerosis- Totaling about 50

  • Symptoms

  • Multiple SclerosisProgressive-relapsingSecondary ProgressivePrimary Progressive Relapsing-Remittinghttp://upload.wikimedia.org/wikipedia/commons/3/3c/Ms_progression_types.svgTwo major classesRelapsing85-90% start this way65% remain

    Progressive10-15% Primary20-25% Secondary

  • Environmental FactorsMore common in people that live farther from the equator

    Sunlight link to MS risk (Vitamin D) Related?

    Virus connection? (HHV-6 and EBV)

  • Environmental FactorPer 100,000 individuals in the population

  • What are the different genetic factors?Human leukocyte antigen (HLA) systemGenes that serve as the major histocompatibility complex (MHC)What is a MHC?

  • MHC I and IIMHC I All nucleated cellsThree polymorphic classes6 possible combinations in the populationHow many can you have?MHC IIMainly dendritic cells, macrophages, and B lymphocytesA heterozygote can inherit six or eight allelesThese are one DQ and DP and one or two DRs

  • MHC II

  • MHC IIThere are two alleles associated with MSDR15 DQ6

    There are two protective alleles HLA-C554 HLA-DRB1*11

  • MHC II and T cell InteractionMacrophageT cell

  • T cells or lymphocytesFour classesCytotoxic, Regulatory, Memory, HelperT-helper cells (TH cells)Secrete small proteins (cytokines, interleukins) Several subtypes to create unique immune responseThis differentiation is unknown, but believed to be through the MHC and peptide sequence recognition

  • InterleukinsA group of cytokines released by lymphocytesMost are produced in CD4+ cells They are believe to promote differentiation

    The paper mentions4, 6, 10, 17, 22, 23, 25, 27

    However, the large focus is on 6, 10, 17, 23

  • So, what is so bad about Interleukin 17?Myelinated Schwann CellsComposed of 80% lipid and 20% proteinMyelin Basic Protein, Myelin oligodendrocyte glycoprotein, and?

    Proteolipid ProteinMay assist in compaction, stabilization, and maintenance of myelin sheathshttp://www.google.com/imgres?imgurl=http://www.signaling-gateway.org/update/images/updates_thumbs/nri2325.jpg&imgrefurl=http://www.signaling-gateway.org/update/updates/200805/index.html&usg=__CDzMs7VIzAxllHFTQG85ytleaWY=&h=80&w=80&sz=3&hl=en&start=13&um=1&itbs=1&tbnid=PXKQovmvAyZWWM:&tbnh=74&tbnw=74&prev=/images%3Fq%3Dinterleukin%2B17%26um%3D1%26hl%3Den%26sa%3DN%26tbs%3Disch:1

  • Now what happens in MSProteolipid ProteinTH-17 cellsAxonMyelin

  • Now what happens in MSProteolipid ProteinTH-17 cells

  • Why is this bad?Sodium Channels along axon are exposed (lose Nodes of Ranvier)Demyelination causes a loss of action potential in the cell. Neurons cannot send signals or signals are sent at a very slow rate

  • Other information you may need to know Experimental Autoimmune EncephalomyelitisEAE model Equivalent model in mice

    Transforming growth factor Beta (TGF-)Development of TH-17 cells Development of Regulatory T cellsBlocks the activation of lymphocytes and monocytes

  • Where are we going?The paper wants to show if TGF- promotes pathogenic function of TH-17 cellsOr, does the immunoregulatory effects of TGF- play in TH-17 cells sensitivity and suppressionHere, they look at responses of activated myelin-reactive T cells with treatments of IL-23 or TGF- and IL-6

  • ReferencesMcGeachy, M. J., K. S. Bak-Jensen, Y. Chen, C. M. Tato, W. Blumenschein, T. McClanahan, and D. J. Cua. 2007. TGF- and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated patholgy. Nature Immuno. 8: 1390-97. Langrish, C. L. et al. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201: 233-240. Abbas, A. K. and A. H. Litchman. 2006. Basic Immunology: 3rd edition. Saunders. Victor, M., Ropper, A. H., and R. D. Adams. 2000. Adams & Victors Principles of Neurology: 7th Edition. McGraw-Hill Professional.

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