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 PresentationTRANSCRIPT
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? – They all work for Schering-Plough
Biopharma– Merged 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?
-Crohn’s Disease-Lupus -Scleroderma
- Rheumatoid arthritis - Multiple Sclerosis- Totaling about 50
Symptoms
Multiple SclerosisProgressive-relapsing
Secondary Progressive
Primary Progressive
Relapsing-Remitting
http://upload.wikimedia.org/wikipedia/commons/3/3c/Ms_progression_types.svg
• Two major classes– Relapsing
• 85-90% start this way• 65% remain
– Progressive• 10-15% Primary• 20-25% Secondary
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)
Environmental Factor
Per 100,000 individuals in the population
What are the different genetic factors?
• Human leukocyte antigen (HLA) system– Genes that serve as the major histocompatibility
complex (MHC)
What is a MHC?
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
MHC II
MHC II
α1
α2
β1
β2
membrane
Peptide-binding cleft•There are two alleles associated
with MS•DR15 •DQ6
•There are two protective alleles •HLA-C554 •HLA-DRB1*11
MHC II and T cell Interaction
Macrophage
T cell
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
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
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
Cell Body
Myelin Sheath
Dendrites
Axon
Myelinated Schwann CellProteolipid
Protein
Axon
Now what happens in MS• Proteolipid
Protein• TH-17 cells
• Axon• Myelin
Now what happens in MS
• Proteolipid Protein
• TH-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 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
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
ReferencesMcGeachy, 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.