Multiple Sclerosis and Neuroinflammation: Considering Gender differences to design therapeutic agents HALINA OFFNER
|
|
- Luke McDaniel
- 6 years ago
- Views:
Transcription
1 Multiple Sclerosis and Neuroinflammation: Considering Gender differences to design therapeutic agents HALINA OFFNER
2 Sex differences in autoimmune disease Ratio Target Sex distribution of major autoimmune diseases Rose N. Am J Path 173(3) % of the people affected with autoimmune diseases are women affecting 5 to 8% of the population or 14.7 to 23.5 million people Numbers above bars-total number of disease cases (X 1,000,000) in the U.S. Whitacre C. Nature Immunology 2(9) 2001
3 Understanding Multiple Sclerosis and EAE MS - is a severe disorder of the CNS -characterized by chronic inflammation, myelin loss, gliosis, varying degrees of axonal and oligodendrocyte pathology and progressive neurological dysfunction Experimental autoimmune encephalomyelitis (EAE)- is the prevailing animal model for MS -induced in genetically susceptible rodent strains, upon immunization with spinal cord homogenates, myelin or specific myelin peptides in combination with adjuvant (active EAE) -and by adoptive transfer of encephalitogenic CD4+ T cells (passive EAE) Typically thought of as a Th1/Th17-mediated disease -although other cellular players (eg, APC) also play a role in the early and progressive events of the immune reaction leading to inflammation and CNS damage
4 Increased numbers of antigen presenting cells in the CNS increase susceptibility to and severity of EAE in female mice T cell response to foreign antigens increases numbers of activated T cells in female vs. male CNS (may be influenced by sex steroids) CNS T cells recruit higher numbers of APC Increased APCs enhance encephalitogenic activity of myelin-specific T cells, thus producing high susceptibility phenotype
5 Gender-based Immune differences Stronger immune response Higher APC, CD4 + Th2 and immunoglobulin responses (under estrogen influence) Severe inflammation and enhanced CD4 + Th1 & CD8 + T cell activity (under androgen influence) Fundamental differences in immune function may require different immunomodulatory strategies in females vs. males
6 Complex regulatory balance between the detrimental and beneficial effects of immune cells in MS Th2 IFN-g, TNF-a, IL-6, IL-17 Th1 IL-4, IL-10 T reg NK?? CD8 + T Mast Protection Disease
7 A model for the multifactorial nature of autoimmune disease- Sex hormones represent an important modulatory factor in the immune and autoimmune response Whitacre C. Nature Immunology 2(9) 2001
8 Recent increase in the incidence rates of MS onset in females as compared to males Figure: Annual age- and sex-adjusted incidence rate (95% CI) of multiple sclerosis in Lorraine, France according to year of onset. Debouverie M. Journal of Neurological Sciences
9
10
11
12
13 Do the benefits of vitamin D 3 show a female bias in humans?
14 Facts that link vitamin D and MS 1921: MS cases increase with distance from the equator (C.B. Davenport) The decrease in MS cases with increasing UV light has been documented in q USA q UK q Australia
15 MS cases decrease with increasing UV light exposure MS risk (cases per 100,000 people) UV light availability (December 25)
16 Vitamin D levels decrease with distance from the equator MS risk (cases per 100,000 people) UV light availability (December 25) Low Serum 25-hydroxyvitamin D 3 High Low
17 UV light catalyzes the first step in vitamin D 3 synthesis Calcitriol OH OH OH OH 25-hydroxylase 1a-hydroxylase 24-hydroxylase OH OH Serum 25-hydroxyvitamin D 3 levels correlate with exposure to UV light
18 The benefits of vitamin D 3 showed a female bias in mice with EAE Female spinal cord histopathology ~12 nmol/l ~82 nmol/l serum 25-OH-D 3 Spach & Hayes, J. Immunol. 175:4119, 2005
19 Estrogen was needed for vitamin D 3 to inhibit EAE in female mice Ovariectomy eliminated vitamin D 3 - mediated inhibition of EAE Estrogen replacement restored vitamin D 3 -mediated inhibition of EAE
20 If humans have a similar gender difference in vitamin D metabolism in the CNS ( less CYP24A1 transcripts in females), then sunlight deprivation would increase the MS risk more significantly in women then in men. Which could explain higher incidence of MS in females.
21 Hypotheses There may be a female bias in the protective effects of vitamin D 3 in MS Vitamin D 3 insufficiency may contribute to the high female:male sex ratio in MS Life style changes linked to insufficient sunlight exposure may be increasing the female:male sex ratio in MS q q q Women in the work force Indoor life style Sunscreen use Declining ovarian function and limited vitamin D 3 supplies may be driving the transition from RRMS to CPMS
22 Recombinant T-Cell Receptor Ligand MHC II Molecule General RTL Molecule RTL Molecular Structure Antigenic Peptide Interchangeable Peptide p- β linker a1 b1 a 1 b 1 a2 a 2 b2 b 2 Targets antigen-specific receptors on T-Cells a1 b1 MHC II α-β linker Antigen Presenting Cell α2 and β2 subunits deleted Peptide = 10-20aa α-βlinker = 0-10aa P-βlinker = 14aa MW = 25,000 (210aa) Produced in E. coli MS Collaborative Research Group
23 RTL treatment of EAE at the onset of disease FEMALES MALES
24 RTL551 Reverses T-cell Infiltration in Spinal Cords of Male and Female C57BL/6 Mice with EAE Onset 3 days post-treatment Vehicle T Cell Infiltration 3 days post-treatment RTL MS Collaborative Research Group
25 Major Inclusion Criteria for Phase I Study Fulfill McDonald Criteria for MS Confirmed diagnosis of RRMS or SPMS EDSS 0.0 to 6.5 No clinical exacerbations within 8 wks HLA-DR2 positive males and females >18 and <65 years of age MS Collaborative Research Group
26 Trial Design and Sites Six cohorts (escalating doses ranging from 2mg to 200mg) q Up to six subjects/cohort (4 drug; 2 placebo) q DSMB review q 34 subjects (males and females) enrolled and followed over 90 days Clinical Sites: q University of Maryland, College Park q OHSU, Portland q Kansas University, Kansas City q Indiana University, Indianapolis q Yale, New Haven q Seattle Evergreen MS Collaborative Research Group
27 Results: No MS Disease Activity Included as a safety endpoint to determine if RTL1000 increases MS disease activity q q q q q q Neurologic exam Extended Disability Status Score (EDSS) 25-ft timed walk 9-hole peg test Gadolinium-enhanced magnetic resonance imaging (MRI) Reports of MS exacerbation RTL1000 did not increase MS disease activity by any measure in either females or males MS Collaborative Research Group
28 When and how should sex differences be considered? Sex matters in many clinical diseases and animal disease models (eg. Vitamin D but not RTLs) Pre-clinical studies should include both sexes Disease models such as EAE have mainly used a single gender or gender unspecified animals q Justified as a means of decreasing experimental variability caused by female hormone cycling q Based on assumption that disease mechanisms or treatment effects would be the same for both genders
29 ACKNOWLEDGMENT I would like to thank Colleen E. Hayes, Ph.D., Professor of Biochemistry, University of Wisconsin-Madison for the use of her data in my presentation.
What is Autoimmunity?
Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.
More informationWhat is Autoimmunity?
Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.
More information3rd International Conference on Neurology & Therapeutics.
3rd International Conference on Neurology & Therapeutics www.neuroimmunology.ca Multiple sclerosis is a devastating disease The first description of the disease was mentioned in 14th century In 1838 Dr.
More informationSUSPECTED MECHANISMS INVOLVED IN MS AND PUTATIVE INTERACTIONS WITH HEPATITIS B VACCINE IN MS
SUSPECTED MECHANISMS INVOLVED IN MS AND PUTATIVE INTERACTIONS WITH HEPATITIS B VACCINE IN MS Emmanuelle Waubant, M.D. Olaf Stüve, M.D., PhD UCSF MS Center, San Francisco March 11, 2002 EPIDEMIOLOGY OF
More informationPotential Rebalancing of the Immune System by Anti-CD52 Therapy
Potential Rebalancing of the Immune System by Anti-CD52 Therapy Johanne Kaplan, PhD VP Neuroimmunology Research Genzyme March 26, 2013 RESTRICTED USE SEE TRAINING MEMO 2011 DO Genzyme NOT 1COPY Corporation
More informationTh1/Th17 Cytokine Dysregulation during Different Stages of Multiple Sclerosis
Th1/Th17 Cytokine Dysregulation during Different Stages of Multiple Sclerosis Benjamin M. Segal, M.D. Holtom-Garrett Professor of Neurology Director, Multiple Sclerosis Program University of Michigan Disclosures
More informationRelevant Disclosures
6/18/215 Therapeutic developments for autoimmune demyelinating diseases: Musings from a MD (Mouse Doctor) Michael K. Racke, M.D. May 28, 215 Relevant Disclosures Editorial Boards for Journal of Neuroimmunology,
More informationHot Topics Multiple Sclerosis. Natalie Parks, MD, FRCPC Assistant Professor, Dalhousie University June 27, 2018
Hot Topics Multiple Sclerosis Natalie Parks, MD, FRCPC Assistant Professor, Dalhousie University June 27, 2018 Disclosures Natalie Parks has received compensation from Biogen, EMD Serono, Roche, and Sanofi
More informationMEDIA BACKGROUNDER. Multiple Sclerosis: A serious and unpredictable neurological disease
MEDIA BACKGROUNDER Multiple Sclerosis: A serious and unpredictable neurological disease Multiple sclerosis (MS) is a complex chronic inflammatory disease of the central nervous system (CNS) that still
More informationMultiple Sclerosis. Biology 12 Nervous System Project
Multiple Sclerosis Biology 12 Nervous System Project Overview Multiple Sclerosis (MS) is a progressive and unpredictable disorder that affects the central nervous system. Figure 1: The central nervous
More informationPhD thesis. The role of complement in Experimental Autoimmune Encephalomyelitis, the mouse modell of Multiple Sclerosis
PhD thesis The role of complement in Experimental Autoimmune Encephalomyelitis, the mouse modell of Multiple Sclerosis Nóra Terényi Supervisor: Prof. Anna Erdei Biology Doctorate School Immunology Program
More informationNeuroimmunology. Innervation of lymphoid organs. Neurotransmitters. Neuroendocrine hormones. Cytokines. Autoimmunity
Neuroimmunology Innervation of lymphoid organs Neurotransmitters Neuroendocrine hormones Cytokines Autoimmunity CNS has two ways of contacting and regulating structures in the periphery Autonomic
More informationKaspar Rufibach Methods, Collaboration, and Outreach Group (MCO) Department of Biostatistics, Roche Basel
Construction of an Estimand in a Clinical Trial on Progressive Multiple Sclerosis Kaspar Rufibach Methods, Collaboration, and Outreach Group (MCO) Department of Biostatistics, Roche Basel Acknowledgments
More informationPrimary oligodendropathy is not a trigger of CNS autoimmunity
Primary oligodendropathy is not a trigger of CNS autoimmunity Ari Waisman Institute for Molecular Medicine University Medical Center, JGU Mainz 1 How is an anti-myelin immune response initiated? Secondary
More informationAutoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens
Autoimmunity Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmune disease can be caused to primary defects in B cells, T cells and possibly
More informationDepartment of Neurology, Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan , Iran 2
Hindawi Publishing Corporation Multiple Sclerosis International Volume 2012, Article ID 452541, 7 pages doi:10.1155/2012/452541 Clinical Study Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting
More informationNeurodegeneration and macrophages; a beneficial or harmful role for macrophages and microglia in neuronal damage during multiple sclerosis
Neurodegeneration and macrophages; a beneficial or harmful role for macrophages and microglia in neuronal damage during multiple sclerosis Marlijn van der Poel Writing assignment: literature review October
More informationFactors Which Predispose to the Onset of Autoimmune Disease. A Senior Honors Thesis
Factors Which Predispose to the Onset of Autoimmune Disease A Senior Honors Thesis Presented in Partial Fulfillment of the Requirements for graduation with distinction in Biology in the College of Biological
More informationClinician s view of Benefit-Risk
Clinician s view of Benefit-Risk Gordon Francis, MD Novartis, Clinical Development Clinician s View of Benefit-Risk: a need for reliable metrics A tale of 3 drugs Natalizumab MS Crohn s Disease Fingolimod
More informationGender Differences in Autoimmune Diseases
//9 Impact of Gender on the Pathogenesis of Crohn s Disease Theresa T. Pizarro Department of Pathology, CWRU Gender Differences in Autoimmune Diseases n Autoimmune diseases affect ~.7-. million people
More informationCOPAXONE DEVELOPMENT AND STATE OF THE ART RUTH ARNON. The Weizmann Institute of Science Rehovot, ISRAEL
COPAXONE DEVELOPMENT AND STATE OF THE ART RUTH ARNON The Weizmann Institute of Science Rehovot, ISRAEL Research in academic institutions is mostly basic, namely curiosity-driven In some cases it reaches
More informationB-cell. Astrocyte SCI SCI. T-cell
RF #2015 P-01 PI: Azizul Haque, PhD Grant Title: Targeting Enolase in Spinal Cord Injury 12-month Technical Progress Report Progress Report (First Six Months): Enolase is one of the most abundantly expressed
More informationDeterminants of Immunogenicity and Tolerance. Abul K. Abbas, MD Department of Pathology University of California San Francisco
Determinants of Immunogenicity and Tolerance Abul K. Abbas, MD Department of Pathology University of California San Francisco EIP Symposium Feb 2016 Why do some people respond to therapeutic proteins?
More informationBachelor of Chinese Medicine ( ) AUTOIMMUNE DISEASES
Bachelor of Chinese Medicine (2002 2003) BCM II Dr. EYT Chan February 6, 2003 9:30 am 1:00 pm Rm 134 UPB AUTOIMMUNE DISEASES 1. Introduction Diseases may be the consequence of an aberrant immune response,
More informationMucosal Immune System
Exam Format 100 points - 60 pts mandatory; 40 points where 4, 10 point questions will be chosen Some open-ended questions, some short answer. Kuby question Cytokines Terminology How do cytokines achieve
More informationEfficacy of interferon beta-1b as a first-line treatment in patients with Radiologically Isolated Syndrome
Efficacy of interferon beta-1b as a first-line treatment in patients with Radiologically Isolated Syndrome A CONTROLLED, RANDOMIZED, MULTICENTER, DOUBLE-BLIND CLINICAL TRIAL FINAL DEGREE PROJECT Author:
More informationVesicular Demyelination in MS A Pattern of Humoral Immune Pathology Multiple Sclerosis: B-Cells Take Center Stage
Vesicular Demyelination in MS A Pattern of Humoral Immune Pathology Multiple Sclerosis: B-Cells Take Center Stage Stephen L. Hauser, M.D. CD2 B cells in an MS lesion CD2 B cells in an MS lesion 1 CD138
More information1996 vs 2013 MS Phenotype Descriptions of Progressive Disease
Learning Objectives Upon completion, participants should be able to: Describe methods of distinguishing among RRMS, SPMS, and PPMS Incorporate available evidence about emerging and recently approved novel
More informationTop 10 Research Findings of 2016
Top 10 Research Findings of 2016 NMSS Regional Summit 2017 June 10, 2017 Rebecca Spain, MD, MSPH VA Portland Health Care System Oregon Health & Science University Disclosures Research support: NMSS Department
More informationCathepsin S Inhibitors for the Treatment of Inflammatory Bowel Disease. Therapeutic Area Partnerships Presentation.
Inhibitors for the Treatment of Inflammatory Bowel Disease Therapeutic Area Partnerships Presentation November 29, 2012 Cathepsin Cysteine Proteinases Fibrosis Cathepsin O Cathepsin B Cathepsin C Cathepsin
More informationInternational Journal of Scientific & Engineering Research Volume 9, Issue 8, Augsut ISSN
International Journal of Scientific & Engineering Research Volume 9, Issue 8, Augsut-2018 249 HLA-DR as a critical player in Vitamin-D associated Multiple sclerosis pathogenesis. Abida Zulfiqar, Dr. Musarrat
More informationDOWNLOAD OR READ : MULTIPLE SCLEROSIS THE HISTORY OF A DISEASE PDF EBOOK EPUB MOBI
DOWNLOAD OR READ : MULTIPLE SCLEROSIS THE HISTORY OF A DISEASE PDF EBOOK EPUB MOBI Page 1 Page 2 multiple sclerosis the history of a disease multiple sclerosis the history pdf multiple sclerosis the history
More informationTheiler s Murine Encephalomyelitis Virus-Induced CNS Autoimmunity
Theiler s Murine Encephalomyelitis Virus-Induced CNS Autoimmunity Virus-induced molecular mimicry is part of a mouse model of multiple sclerosis that is providing insights about the disease in humans Julie
More informationIntroduction and overview of sex differences in MS risk and course:
Introduction and overview of sex differences in MS risk and course: Tanuja Chitnis MD Associate Professor in Neurology, HMS Medical Director, CLIMB Study, BWH Director, Partners Pediatric MS Center, MGH
More informationReview Article The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
Multiple Sclerosis International, Article ID 285245, 17 pages http://dx.doi.org/10.1155/2014/285245 Review Article The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis
More informationGlioblastoma and CNS tumors
Glioblastoma and CNS tumors PRECEPTORSHIP PROGRAMME IMMUNO-ONCOLOGY Amsterdam, 1 October 2016 Patrick Roth Department of Neurology and Brain Tumor Center University Hospital Zurich Immunology in the CNS
More informationAUBAGIO (teriflunomide) oral tablet
AUBAGIO (teriflunomide) oral tablet Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy
More informationFast Facts: Multiple Sclerosis
Fast Facts Fast Facts: Multiple Sclerosis George D Perkin and Jerry S Wolinsky Second edition 2006 Health Press Ltd. www.fastfacts.com Fast Facts Fast Facts: Multiple Sclerosis Second edition George D
More informationImmunological Tolerance
Immunological Tolerance Introduction Definition: Unresponsiveness to an antigen that is induced by exposure to that antigen Tolerogen = tolerogenic antigen = antigen that induces tolerance Important for
More informationOcrevus (ocrelizumab)
Ocrevus (ocrelizumab) Policy Number: 5.01.629 Last Review: 04/2018 Origination: 05/2017 Next Review: 04/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Ocrevus
More informationTolerance 2. Regulatory T cells; why tolerance fails. FOCiS. Lecture outline. Regulatory T cells. Regulatory T cells: functions and clinical relevance
1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails
More informationT cell maturation. T-cell Maturation. What allows T cell maturation?
T-cell Maturation What allows T cell maturation? Direct contact with thymic epithelial cells Influence of thymic hormones Growth factors (cytokines, CSF) T cell maturation T cell progenitor DN DP SP 2ry
More informationImmune Regulation and Tolerance
Immune Regulation and Tolerance Immunoregulation: A balance between activation and suppression of effector cells to achieve an efficient immune response without damaging the host. Activation (immunity)
More informationPeer review correspondence
Highly polarized Th17 cells induce EAE via a T-bet-independent mechanism Heather M. Grifka-Walk, Stephen J. Lalor and Benjamin M. Segal Corresponding author: Benjamin Segal, Holtom-Garrett Program in Neuroimmunology
More informationMOLECULAR IMMUNOLOGY Manipulation of immune response Autoimmune diseases & the pathogenic mechanism
MOLECULAR IMMUNOLOGY Manipulation of immune response Autoimmune diseases & the pathogenic mechanism SCHMAIEL SHIRDEL CONTENT 2 Introduction Autoimmune diseases Classification Involved components Autoimmune
More informationMRI in Multiple Sclerosis Features of Cerebral Atrophy with special focus on Multiple Sclerosis. E.W. Radue K. Bendfeldt Till Sprenger
MRI in Multiple Sclerosis Features of Cerebral Atrophy with special focus on Multiple Sclerosis E.W. Radue K. Bendfeldt Till Sprenger Medical Image Analysis Center University Hospital Basel www. miac.ch
More informationSupporting Information
Supporting Information Stegbauer et al. 10.1073/pnas.0903602106 SI Methods Analysis of Plasma Renin Activity (PRA) and ACE Activity. PRA and serum ACE activity levels were determined by RIA (RENCTK, DiaSorin;
More informationTECFIDERA (dimethyl fumarate) oral capsule
TECFIDERA (dimethyl fumarate) oral capsule Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy
More informationHORMONES AND DENDRITIC CELLS: INFLUENCES ON THE INITIATION OF THE AUTOIMMUNE DISEASE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS DISSERTATION
HORMONES AND DENDRITIC CELLS: INFLUENCES ON THE INITIATION OF THE AUTOIMMUNE DISEASE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS DISSERTATION Presented in Partial Fulfillment of the Requirements for the
More informationThe Role of NOTCH3 Signaling in T Helper Cell Differentiation and Induction of EAE
University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses 2016 The Role of NOTCH3 Signaling in T Helper Cell Differentiation and Induction of EAE Furkan
More informationDiseases of Immunity 2017 CL Davis General Pathology. Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc.
Diseases of Immunity 2017 CL Davis General Pathology Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc. Autoimmunity Reflects a loss of immunologic tolerance Mechanisms Auto-antibodies
More informationPEDIATRIC MULTIPLE SCLEROSIS
PEDIATRIC MULTIPLE SCLEROSIS N E U R O G E N O M I C S L A B O R AT O R Y M U LT I P L E S C L E R O S I S C E N T E R S H E B A M E D I C A L C E N T E R Definitions Multiple sclerosis (MS), a chronic
More informationENDOGENOUS OPIOIDS AND MULTIPLE SCLEROSIS
The Pennsylvania State University The Graduate School Program in Cellular and Molecular Biology ENDOGENOUS OPIOIDS AND MULTIPLE SCLEROSIS A Dissertation in Cellular and Molecular Biology by Kristen Rahn
More informationOff-Label Treatments. Clinical Trials for Recurrent GBM UCSF Radiation Oncology Course: Management of Recurrent Disease. Outline
Off-Label Treatments Clinical Trials for Recurrent GBM UCSF Radiation Oncology Course: Management of Recurrent Disease Jennifer Clarke, MD, MPH Assistant Professor Division of Neuro-Oncology Depts of Neurological
More informationWhat Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis?
Int. J. Mol. Sci. 2012, 13, 12665-12709; doi:10.3390/ijms131012665 Review OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms What Do Effective Treatments for
More informationLife Long Brain Health and DMT Comparative Effectiveness
Life Long Brain Health and DMT Comparative Effectiveness Timothy Vollmer, MD Professor of Neurology University of Colorado Denver Medical Director- RMMSC and Co-Director Rocky Mountain MS Center at CU
More informationGILENYA (fingolimod) oral capsule
GILENYA (fingolimod) oral capsule Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy Coverage
More informationSelf-tolerance. Lack of immune responsiveness to an individual s own tissue antigens. Central Tolerance. Peripheral tolerance
Autoimmunity Self-tolerance Lack of immune responsiveness to an individual s own tissue antigens Central Tolerance Peripheral tolerance Factors Regulating Immune Response Antigen availability Properties
More informationInternational Symposium of Environmental Medicine
International Symposium of Environmental Medicine Including Asthma, Rhinitis Eczema, Uti Urticaria i (hives) Drug, Food, and Insect allergy Asthma: ~3 3 10 8 patients in the world 250,000 asthma deaths
More informationThe anti-inflammatory enzyme A20 in the neuropathology of Multiple Sclerosis
More Than Neurons, 1-3 December, Turin The anti-inflammatory enzyme A20 in the neuropathology of Multiple Sclerosis Dr. Simona Perga, PhD Neuroscience Institute Cavalieri Ottolenghi (NICO) & Multiple Sclerosis
More informationMultiple Sclerosis. By: Selena Fucci April 22, 2016
Multiple Sclerosis By: Selena Fucci April 22, 2016 Abstract: Multiple Sclerosis, MS, is a chronic neurological disorder in the brain and spinal cord involving inflammation and demyelination of the central
More informationCarolyn Taylor, M.D. Swedish Neuroscience Center
Carolyn Taylor, M.D. Swedish Neuroscience Center When should disease modifying therapy be discontinued in MS? Should we be using aggressive treatments earlier in the MS disease course and reserving the
More informationSupplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured
Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured under Th0, Th1, Th2, Th17, and Treg conditions. mrna
More informationProgressive Multiple Sclerosis
Progressive Multiple Sclerosis Definitions, Clinical Course and Emerging Therapies M. Mateo Paz Soldán, MD, PhD Neurology Service, VA Salt Lake City HCS Assistant Professor of Neurology, University of
More informationRelapses Matter A GUIDE TO REPORTING MULTIPLE SCLEROSIS SYMPTOMS
Relapses Matter A GUIDE TO REPORTING MULTIPLE SCLEROSIS SYMPTOMS Scientific Review by: COLLEEN HARRIS, MN, NP, MSCN Nurse Practitioner/Coordinator University of Calgary MS Program Calgary, Alberta The
More informationNeuroVia, NV1205 Clinical Trials
NeuroVia, NV1205 Clinical Trials Developing a safe and effective treatment for children with Childhood Cerebral Adrenoleukodystrophy Masoud Mokhtarani MD Chief Medical Officer ALD Life Family Weekend Meeting,
More informationCentral nervous system demyelinating diseases - Multiple sclerosis -
Central nervous system demyelinating diseases - Multiple sclerosis - Amilton Antunes Barreira Department of Neurology Faculdade de Medicina and Hospital das Clínicas de Ribeirão Preto - USP Diseases of
More informationSUN HEALTH TECHNOLOGIES
SUN HEALTH TECHNOLOGIES CORRELATION BETWEEN VITAMIN D, UVB, AND MS Researchers are finding a strong association between vitamin D levels, UVB exposure and multiple sclerosis (MS). According to the Mayo
More informationTITLE: Harnessing GPR17 Biology for Treating Demyelinating Disease
AD Award Number: W81XWH-10-1-0723 TITLE: Harnessing GPR17 Biology for Treating Demyelinating Disease PRINCIPAL INVESTIGATOR: Qing Lu, Ph.D. CONTRACTING ORGANIZATION: University of Texas Southwestern Medical
More informationMeeting in Valencia - September 2014 New possibilities about causes of common autoimmune diseases: rheumatoid arthritis, ankylosing spondylitis, multi
Meeting in Valencia - September 2014 Professor Alan Ebringer B.Sc, MD, FRCP. FRACP, FRCPath. Professor of Immunology, King s College, London, U.K. Some autoimmune diseases are caused by bacterial infections.
More informationPEDIATRIC MULTIPLE SCLEROSIS CLINICAL AND TRANSCRIPTIONAL ASPECTS M U L T I P L E S C L E R O S I S C E N T E R
PEDIATRIC MULTIPLE SCLEROSIS CLINICAL AND TRANSCRIPTIONAL ASPECTS M U L T I P L E S C L E R O S I S C E N T E R Gurevich M. PEDIATRIC MS Pediatric MS is defined as onset MS under the age of 18 years Pediatric
More informationDemyelinating Diseases: Multiple Sclerosis January 10, 2018 Dr. Ostrow
Demyelinating Diseases: Multiple Sclerosis January 10, 2018 Dr. Ostrow Reading: Robbins & Cotran, 9 th edition, pp 1283-1286 Robbins Basic Pathology, 9 th edition, 832-835 Overview: Grossly, myelin is
More information2013 MS Phenotype Descriptions: Relapsing MS 1
2013 MS Phenotype Descriptions: Relapsing MS 1 Disease-Modifying Therapies? which can be found in its entirety at. Clinically isolated syndrome (CIS) Not Active a Active a,b Relapsing-remitting disease
More informationTHE NATURAL HISTORY OF MS: DIAGNOSIS, CLINICAL COURSE, AND EPIDEMIOLOGY
THE NATURAL HISTORY OF MS: DIAGNOSIS, CLINICAL COURSE, AND EPIDEMIOLOGY John R. Rinker, II, MD University of Alabama at Birmingham June 2, 2016 DISCLOSURES Research Support: Biogen Idec; Department of
More informationLESSON 2: THE ADAPTIVE IMMUNITY
Introduction to immunology. LESSON 2: THE ADAPTIVE IMMUNITY Today we will get to know: The adaptive immunity T- and B-cells Antigens and their recognition How T-cells work 1 The adaptive immunity Unlike
More informationThe Ying and Yang of IFN-γ in Autoimmunity
The Ying and Yang of IFN-γ in Autoimmunity Chander Raman, Ph.D. Early Late Autoimmune neuroinflammation Experimental autoimmune encephalomyelitis (EAE) Rheumatoid arthritis (RA) Autoimmune neuroinflammation
More informationMS Research-Your Questions Answered. Bruce Bebo, PhD Executive Vice President, Research
MS Research-Your Questions Answered Bruce Bebo, PhD Executive Vice President, Research Overview 1. Multiple Sclerosis 401 2. Key advances MS research 3. What the Society is doing to find solutions for
More informationMULTIPLE SCLEROSIS Update
MULTIPLE SCLEROSIS Update E. Torage Shivapour, M.D. Clinical Professor Department of Neurology University of Iowa Hospitals & Clinics Disclosures I do not have any disclosures. Multiple Sclerosis Most
More informationDisclosure 7/2/2018. Consultant : Ultragenyx, Alexion, Ferrings. Research grant support: Ultragenyx, Shire, Amgen. Clinical Trial : Ultragynyx, Amgen
Pisit (Duke) Pitukcheewanont, MD, FAAP Clinical Director, Pediatric Bone Program, Center for Diabetes, Endocrinology & Metabolism Children s Hospital Los Angeles Professor of Clinical Pediatrics The Keck
More informationS. No Topic Class No Date
S. No Topic Class No Date 1 Introduction 2 3 4 5 6 7 Fundamentals of Immunology Definitions and basic terms Types of immunity Organs of immune system Cells of immune system Innate immunity PAMPs PRRs Phagocytosis
More informationSolution key Problem Set
Solution key- 7.013 Problem Set 6-2013 Question 1 a) Our immune system is comprised of different cell types. Complete the table below by selecting all correct cell types from the choices provided. Cells
More informationSignificance of the MHC
CHAPTER 7 Major Histocompatibility Complex (MHC) What is is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) Significance of the MHC role in immune response role in organ
More informationOligodendrocyte/myelin injury and repair as a function of the central nervous system environment
Clinical Neurology and Neurosurgery 108 (2006) 245 249 Oligodendrocyte/myelin injury and repair as a function of the central nervous system environment Jack Antel Department of Neurology & Neurosurgery,
More informationACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT
ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes
More informationBiologics and Beyond: Treatment of Multiple Sclerosis. Rita Jebrin, PharmD, BCPS
Biologics and Beyond: Treatment of Multiple Sclerosis Rita Jebrin, PharmD, BCPS Disclosure Information Biologics and Beyond: Treatment of Multiple Sclerosis Rita Jebrin, PharmD, BCPS I have no financial
More informationThe Pennsylvania State University. The Graduate School. The Huck Institutes of Life Sciences REGULATORY ROLE OF NKT CELLS ON EFFECTS OF
The Pennsylvania State University The Graduate School The Huck Institutes of Life Sciences REGULATORY ROLE OF NKT CELLS ON EFFECTS OF 1,25(OH) 2 D 3 IN MICE WITH EAE A Thesis in Cell and Developmental
More informationTolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases. Abul K. Abbas UCSF
Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases Abul K. Abbas UCSF Balancing lymphocyte activation and control Activation Effector T cells Tolerance Regulatory T cells
More informationCellular Pathology of immunological disorders
Cellular Pathology of immunological disorders SCBM344 Cellular and Molecular Pathology Witchuda Payuhakrit, Ph.D (Pathobiology) witchuda.pay@mahidol.ac.th Objectives Describe the etiology of immunological
More informationModulation of the immune system by UV radiation: more than just the effects of vitamin D?
Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Prue H. Hart*, Shelley Gorman* and John J. Finlay-Jones Abstract Humans obtain most of their vitamin D through
More informationGILENYA (fingolimod) oral capsule
GILENYA (fingolimod) oral capsule Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Pharmacy Coverage
More informationCellular Immune response. Jianzhong Chen, Ph.D Institute of immunology, ZJU
Cellular Immune response Jianzhong Chen, Ph.D Institute of immunology, ZJU Concept of adaptive immune response T cell-mediated adaptive immune response I. Concept of immune response A collective and coordinated
More informationCELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM.
!! www.clutchprep.com CONCEPT: OVERVIEW OF HOST DEFENSES The human body contains three lines of against infectious agents (pathogens) 1. Mechanical and chemical boundaries (part of the innate immune system)
More informationthe HLA complex Hanna Mustaniemi,
the HLA complex Hanna Mustaniemi, 28.11.2007 The Major Histocompatibility Complex Major histocompatibility complex (MHC) is a gene region found in nearly all vertebrates encodes proteins with important
More informationThe Adaptive Immune Responses
The Adaptive Immune Responses The two arms of the immune responses are; 1) the cell mediated, and 2) the humoral responses. In this chapter we will discuss the two responses in detail and we will start
More informationProgress in MS: Current and Emerging Therapies. Presented by: Dr. Kathryn Giles, MD MSc FRCPC Cambridge, Ontario, Canada
Progress in MS: Current and Emerging Therapies Presented by: Dr. Kathryn Giles, MD MSc FRCPC Cambridge, Ontario, Canada Today s Discussion Natural History and Classification of MS Treating MS Management
More informationIMMUNOTOOLS: EFFECT OF NOTCH-DEFICIENT MACROPHAGES TO AUTOIMMUNE DISEASE WIPAWEE WONGCHANA
IMMUNOTOOLS: EFFECT OF NOTCH-DEFICIENT MACROPHAGES TO AUTOIMMUNE DISEASE 22-02-2017 WIPAWEE WONGCHANA WHAT DO YOU SEE? Allergy Ref: http://carrington.edu/blog/medical/vaccines/smallpox-andsmallpox-vaccine/
More informationCytokines (II) Dr. Aws Alshamsan Department of Pharmaceu5cs Office: AA87 Tel:
Cytokines (II) Dr. Aws Alshamsan Department of Pharmaceu5cs Office: AA87 Tel: 4677363 aalshamsan@ksu.edu.sa Learning Objectives By the end of this lecture you will be able to: 1 Understand the physiological
More informationTolerance 2. Regulatory T cells; why tolerance fails. Abul K. Abbas UCSF. FOCiS
1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails
More informationTumors arise from accumulated genetic mutations. Tumor Immunology (Cancer)
Tumor Immunology (Cancer) Tumors arise from accumulated genetic mutations Robert Beatty MCB150 Mutations Usually have >6 mutations in both activation/growth factors and tumor suppressor genes. Types of
More information