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What Schering-Plough Biopharma?

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?

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What Schering-Plough Biopharma?

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

  2. What Schering-Plough Biopharma? • Pharmaceutical Company • What kind of research is performed at the facility? • Is there a conflict of interest? • They all work for Schering-Plough Biopharma • Merged with Merck in 2009

  3. What is an Autoimmune disease? • Is defined as an immune response against self antigens. • What are some of the major autoimmune diseases? -Crohn’s Disease -Lupus -Scleroderma • - Rheumatoid arthritis • - Multiple Sclerosis • - Totaling about 50

  4. Symptoms

  5. Multiple Sclerosis Progressive-relapsing • Two major classes • Relapsing • 85-90% start this way • 65% remain • Progressive • 10-15% Primary • 20-25% Secondary Secondary Progressive Primary Progressive Relapsing-Remitting http://upload.wikimedia.org/wikipedia/commons/3/3c/Ms_progression_types.svg

  6. Environmental Factors • More common in people that live farther from the equator • Sunlight link to MS risk (Vitamin D) – Related? • Virus connection? (HHV-6 and EBV)

  7. Environmental Factor Per 100,000 individuals in the population

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

  9. MHC I and II • MHC I • All nucleated cells • Three polymorphic classes • 6 possible combinations in the population • How many can you have? • MHC II • Mainly dendritic cells, macrophages, and B lymphocytes • A heterozygote can inherit six or eight alleles • These are one DQ and DP and one or two DR’s

  10. MHC II

  11. MHC II Peptide-binding cleft α1 β1 • There are two alleles associated with MS • DR15 • DQ6 • There are two protective alleles • HLA-C554 • HLA-DRB1*11 α2 β2 membrane

  12. MHC II and T cell Interaction T cell Macrophage

  13. T cells or lymphocytes • Four classes • Cytotoxic, Regulatory, Memory, Helper • T-helper cells (TH cells) • Secrete small proteins (cytokines, interleukins) • Several subtypes to create unique immune response • This differentiation is unknown, but believed to be through the MHC and peptide sequence recognition

  14. Interleukins • A group of cytokines released by lymphocytes • Most are produced in CD4+ cells • They are believe to promote differentiation • The paper mentions • 4, 6, 10, 17, 22, 23, 25, 27 • However, the large focus is on • 6, 10, 17, 23

  15. So, what is so bad about Interleukin 17? • Myelinated Schwann Cells • Composed of 80% lipid and 20% protein • Myelin Basic Protein, Myelin oligodendrocyte glycoprotein, and? • Proteolipid Protein • May assist in compaction, stabilization, and maintenance of myelin sheaths http://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

  16. Cell Body Dendrites Axon Myelin Sheath Axon Myelinated Schwann Cell Proteolipid Protein

  17. Now what happens in MS • Proteolipid Protein • TH-17 cells • Axon • Myelin

  18. Now what happens in MS • Proteolipid Protein • TH-17 cells

  19. 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

  20. Other information you may need to know • Experimental Autoimmune Encephalomyelitis • EAE model • Equivalent model in mice • Transforming growth factor Beta (TGF-β) • Development of TH-17 cells • Development of Regulatory T cells • Blocks the activation of lymphocytes and monocytes

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

  22. References McGeachy, M. J., K. S. Bak-Jensen, Y. Chen, C. M. Tato, W. Blumenschein, T. McClanahan, and D. J. Cua. 2007. TGF-β 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 & Victor’s Principles of Neurology: 7th Edition. McGraw-Hill Professional.

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