BDC Keystone Genetics Type 1 Diabetes. Immunology of diabetes book with Teaching Slides

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "BDC Keystone Genetics Type 1 Diabetes. Immunology of diabetes book with Teaching Slides"

Transcription

1 BDC Keystone Genetics Type 1 Diabetes Immunology of diabetes book with Teaching Slides

2 PRACTICAL Trailnet screens relatives and new onset patients for autoantibodies and HLA when appropriate for free halt-dm1 GAD Dynal commercial laboratory excellent assay re sensitivity BDC has laboratory re outside samples: (only ZnT8 at present and anti-interferon and HLA re DM) Book Immunology diabetes with slides

3 893 newly diagnosed diabetic subjects (Age: 0.92 to yrs) AutoAb to GAD65, ICA512bdc,insulin (IA-2ic, ICA, ZnT8) #4: ZnT8 antibodies: Beta Cell Zinc Transporter* 753 patients, >= 1 autoantibodies (84.3%) 140 patients, negative for all autoantibodies (15.7%) *ZnT8 Patent BDC

4 AB positive DM C-peptide (pg/ml) Diabetes duration (years)

5 AB negative DM C-peptide (pg/ml) , , patient sister Duration of diabetes (years)

6 JDRF npod 37 yo 20 yrs DM Ab- C-peptide=.2 Atkinson PI

7 Islets with Beta Cells

8 Pseudoatrophic islets

9 Monogenic IPEX syndrome Autoimmune Polyendocrine Type 1 Polygenic Autoimmune Polyendocrine Type 2 Type 1A diabetes

10 9 Months of Age

11 Mutation of FoxP3 gene - Controls regulatory T cells Approximately 80% of children with syndrome develop diabetes Bone marrow transplant can reverse

12 APS-I Autoimmune Polyendocrine Syndrome Type 1 Autosomal Recessive mutations AIRE (Autoimmune Regulator) gene Mucocutaneous Candidiasis/Addison s Disease/Hypoparathyroidism 18% Type 1 Diabetes Transcription Factor in Thymus BDC

13 Eisenbarth GS, Gottlieb PA. NEJM 350:

14 RISK OF TYPE 1 DM Proband with DM % Diabetes % Autoantibody+ General Population 0.3% 4% >=1 Antibody Offspring 1% 4.1% Sibling 6% 7.4% Dizygotic Twin 6% 10% Mother 2% 5% Father 4.6% 6.5% Both Parents 10%?? Monozygotic Twin 60% 70-80%

15

16

17 % Diabetes Proband Diabetes Non-Proband Antibodies Non-Proband Diabetes Age N = % Antibody Positive Redondo, Jeffrey, Fain, Eisenbarth, Orban NEJM 359:

18 HLA Insulin production & metabolism Locus Immunity β cell apoptosis protection Unknown function

19 The IDDM2 Locus Predisposing IDDM2 Class I VNTR repeats 21 alleles Insulin Gene (INS) Protective IDDM2 Class III VNTR repeats 15 alleles Insulin Gene (INS) VNTR = Variable Number of Tandem Repeats

20 Antigen Endocytosis APC MHC II CD4 + T cell T Cell Receptor Trimolecular Complex

21 The Major Histocompatibility Complex Human Chromosome 6 Class II Class III Class I DP DQ DR B C A Antigen Processing Genes Complement Proteins Cytokines Class I-like genes and pseduogenes Mouse Chromosome 17 Class III Class II Class I Class I K I-A I-E D L

22 Human Chromosome 6 Class II Class III Class I DP DQ DR B C A Allele: Haplotype: DRB1*0401 DRB1*0401 DQB1*0302 Genotype: DRB1*0401 DQB1*0302 DRB1*0301 DQB1*0201 Type 1 Diabetes: Molecular, Cellular and Clinical immunology

23 HBDI Series: Transmission from Parents with second haplotype not DQ2 or DQ N= 406/333/33/ 79/ 72/ 55/ 55/ 44/ 42/ 38/ 29/ 37/ 4 DQ8 DQ2 0401/ / / / / / / / / / /0503(1401)

24 NEwborn Cohort (NEC) General population cohort (SOC) Sibling/Offspring Cohort screened = 33,096 Enrolled 391 high risk (2.4 %) 456 moderate risk 384 average-low risk 1,231 offspring siblings Total enrolled 2,270

25 Haplotype Sharing Siblings Share Both Haplotypes Family A Haplotypes A B Siblings Share One Haplotype Family B Siblings Share No Haplotypes Family C C D A B C D A B C D HLA-A HLA-DRB Father Mother Father Mother Father Mother Diabetic Proband DAISY Sibling Diabetic Proband DAISY Sibling Diabetic Proband DAISY Sibling HLA-A HLA-DRB A C A C A C A D A C B D

26 % Autoantibody Positive 100 Siblings at high risk 90 (Share 2) Siblings at low risk 80 (Share 0 or 1) N = N = Age (y) % With Diabetes Age (y) Aly et al. PNAS 103:

27 Autoantibody Positive (%) 30 High Risk 25 (no protective alleles) Low Risk (DRB1* or DPB1*0402) Diabetes (%) Age (years) 30 High Risk 25 (no protective alleles) Low Risk (DRB1* or DPB1*0402) Age (years) Baschal et al. Diabetes 56:

28 Transglutaminase autoantibodies (5% celiac disease) 21-Hydroxylase autoantibodies (1% positive: predictive Addison s disease) Sensitive TSH assay (hypothyroidism very common)

29 Spontaneous Animal Models BB rat Homozygosity Lymphopenia (Ch4;Ian) RT1-U U class II (Ch 20) Additional Loci (Ch2,18,X) NOD mouse Polygenic: class II + class I loci + IL-2 linked polymorphism + >12 iddm loci Long-EvansTokushima Rat RT1-U U MHC Homozygosity Chr 11-Cblb gene BDC

30 TCR MHC PEPTIDE INS B:9-23

31 AA Peptide Side Chains I-A g7 Peptide

32 H S L V 9 13 E A L 16 A Y L V C 23 G R E G Barbara Davis Center

33 % of Diabetes Free ins1+, ins2- (n=24) B16:A Insulin ins1-, ins2- (n=31, P<0.0001) Weeks Nakayama et al. Nature 435:

34 ARG(22) GLU GLY CYS VAL LEU TYR LEU ALA(14)

35 TCR MHC PEPTIDE INS B:9-23

36 Antigen Presenting Cell Peptide V V D J J Chr. 14 Chr. 6

37 THOUGHTS IMMUNE MEDIATED DIABETES HAS A NUMBER OF GENETIC CAUSES DEFINING NON-AUTOIMMUNE IMPORTANT HLA ALLELES MAJOR DETERMINANT IN TERMS OF DIAGNOSIS AND PREDICTION TRIALS IN EXTREME RISK PATIENTS PLANNED/UNDERWAY

Targeting the Trimolecular Complex for Immune Intervention. Aaron Michels MD

Targeting the Trimolecular Complex for Immune Intervention. Aaron Michels MD Targeting the Trimolecular Complex for Immune Intervention Aaron Michels MD Disclosures Research Grant from Novartis. Research Grant from NovoNordisk. Take Home Points Type 1 diabetes is an immunologic

More information

Significance of the MHC

Significance 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 information

Significance of the MHC

Significance of the MHC CHAPTER 8 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 information

The Major Histocompatibility Complex (MHC)

The Major Histocompatibility Complex (MHC) The Major Histocompatibility Complex (MHC) An introduction to adaptive immune system before we discuss MHC B cells The main cells of adaptive immune system are: -B cells -T cells B cells: Recognize antigens

More information

Significance of the MHC

Significance of the MHC CHAPTER 8 Major Histocompatibility Complex (MHC) What is MHC? HLA H-2 Minor histocompatibility antigens Peter Gorer & George Sneell (1940) - MHC molecules were initially discovered during studies aimed

More information

17. Immunologic endocrine disorders

17. Immunologic endocrine disorders 17. Immunologic endocrine disorders Devasenan Devendra, MD, and George S. Eisenbarth, MD, PhD Denver, Colo Immune-mediated tissue destruction or disregulation is the cause of multiple common, as well as

More information

Type 1 Diabetes Pathogenesis, Prediction, and Prevention

Type 1 Diabetes Pathogenesis, Prediction, and Prevention Type 1 Diabetes Pathogenesis, Prediction, and Prevention Peter R Baker II, MD 1 and George S Eisenbarth, MD, PhD 2 1. Fellow, Clinical Genetics and Metabolism, University of Colorado Denver; 2. Executive

More information

Autoimmunity. 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 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 information

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction

Basic Immunology. Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Basic Immunology Lecture 5 th and 6 th Recognition by MHC. Antigen presentation and MHC restriction Molecular structure of MHC, subclasses, genetics, functions. Antigen presentation and MHC restriction.

More information

Development of B and T lymphocytes

Development of B and T lymphocytes Development of B and T lymphocytes What will we discuss today? B-cell development T-cell development B- cell development overview Stem cell In periphery Pro-B cell Pre-B cell Immature B cell Mature B cell

More information

Historical definition of Antigen. An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen.

Historical definition of Antigen. An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen. Historical definition of Antigen An antigen is a foreign substance that elicits the production of antibodies that specifically binds to the antigen. Historical definition of Antigen An antigen is a foreign

More information

Antigen Presentation to T lymphocytes

Antigen Presentation to T lymphocytes Antigen Presentation to T lymphocytes Immunology 441 Lectures 6 & 7 Chapter 6 October 10 & 12, 2016 Jessica Hamerman jhamerman@benaroyaresearch.org Office hours by arrangement Antigen processing: How are

More information

The Human Major Histocompatibility Complex

The Human Major Histocompatibility Complex The Human Major Histocompatibility Complex 1 Location and Organization of the HLA Complex on Chromosome 6 NEJM 343(10):702-9 2 Inheritance of the HLA Complex Haplotype Inheritance (Family Study) 3 Structure

More information

HLA and more. Ilias I.N. Doxiadis. Geneva 03/04/2012.

HLA and more. Ilias I.N. Doxiadis. Geneva 03/04/2012. www.ebmt.org HLA and more Ilias I.N. Doxiadis Geneva 03/04/2012 HLA and more HLA and more / Doxiadis 2 Topic of the day Compatibility testing is a type of testing used to ensure compatibility of the system/application/website

More information

Extreme genetic risk for type 1A diabetes

Extreme genetic risk for type 1A diabetes Extreme genetic risk for type 1A diabetes Theresa A. Aly, Akane Ide, Mohamed M. Jahromi, Jennifer M. Barker, Maria S. Fernando, Sunanda R. Babu, Liping Yu, Dongmei Miao, Henry A. Erlich, Pamela R. Fain,

More information

The role of HLA in Allogeneic Hematopoietic Stem Cell Transplantation and Platelet Refractoriness.

The role of HLA in Allogeneic Hematopoietic Stem Cell Transplantation and Platelet Refractoriness. The role of HLA in Allogeneic Hematopoietic Stem Cell Transplantation and Platelet Refractoriness. Robert Liwski, MD, PhD, FRCPC Medical Director HLA Typing Laboratory Department of Pathology Dalhousie

More information

The Major Histocompatibility Complex

The Major Histocompatibility Complex The Major Histocompatibility Complex Today we will discuss the MHC The study of MHC is necessary to understand how an immune response is generated. And these are the extra notes with respect to slides

More information

HLA Antigen Expression in Autoimmune Endocrinopathies

HLA Antigen Expression in Autoimmune Endocrinopathies Physiol. Res. 53: 191-197, 2004 HLA Antigen Expression in Autoimmune Endocrinopathies P. HRDÁ 1,2, I. ŠTERZL 1,2, P. MATUCHA 2, F. KORIOTH 3, A. KROMMINGA 3 1 Institute of Immunology and Microbiology First

More information

DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS

DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS DEFINITIONS OF HISTOCOMPATIBILITY TYPING TERMS The definitions below are intended as general concepts. There will be exceptions to these general definitions. These definitions do not imply any specific

More information

T Cell Differentiation

T Cell Differentiation T Cell Differentiation Ned Braunstein, MD MHC control of Immune Responsiveness: Concept Whether or not an individual makes an immune response to a particular antigen depends on what MHC alleles an individual

More information

Blood Types and Genetics

Blood Types and Genetics Blood Types and Genetics Human blood type is determined by codominant alleles. An allele is one of several different forms of genetic information that is present in our DNA at a specific location on a

More information

Two categories of immune response. immune response. infection. (adaptive) Later immune response. immune response

Two categories of immune response. immune response. infection. (adaptive) Later immune response. immune response Ivana FELLNEROVÁ E-mail: fellneri@hotmail.com, mob. 732154801 Basic immunogenetic terminology innate and adaptive immunity specificity and polymorphism immunoglobuline gene superfamily immunogenetics MHC

More information

Class I Ag processing. TAP= transporters associated with antigen processing Transport peptides into ER

Class I Ag processing. TAP= transporters associated with antigen processing Transport peptides into ER Antigen processing Class I Ag processing TAP= transporters associated with antigen processing Transport peptides into ER Proteosome degrades cytosolic proteins Large, multi-subunit complex Degrades foreign

More information

10/18/2012. A primer in HLA: The who, what, how and why. What?

10/18/2012. A primer in HLA: The who, what, how and why. What? A primer in HLA: The who, what, how and why What? 1 First recognized in mice during 1930 s and 1940 s. Mouse (murine) experiments with tumors Independent observations were made in humans with leukoagglutinating

More information

Autoimmune diseases. Autoimmune diseases. Autoantibodies. Autoimmune diseases relatively common

Autoimmune diseases. Autoimmune diseases. Autoantibodies. Autoimmune diseases relatively common Autoimmune diseases Fundamental abnormality: the adaptive immune system is triggered by self antigens to initiate a sustained immune response against self molecules that results in tissue injury Specificity

More information

T cell development October 28, Dan Stetson

T cell development October 28, Dan Stetson T cell development October 28, 2016 Dan Stetson stetson@uw.edu 441 Lecture #13 Slide 1 of 29 Three lectures on T cells (Chapters 8, 9) Part 1 (Today): T cell development in the thymus Chapter 8, pages

More information

Sustained adaptive immune response to self antigens may or may not result in tissue injury according to particular host genetics

Sustained adaptive immune response to self antigens may or may not result in tissue injury according to particular host genetics Autoimmune diseases Fundamental abnormality: the adaptive immune system is triggered by self antigens to initiate a sustained immune response against self molecules that results in tissue injury Specificity

More information

Staging of Type 1 Diabetes: Clinical Implications. April Deborah Hefty, MN, RN, CDE.

Staging of Type 1 Diabetes: Clinical Implications. April Deborah Hefty, MN, RN, CDE. Staging of Type 1 Diabetes: TT Clinical Implications April 2016 Deborah Hefty, MN, RN, CDE dhefty@benaroyaresearch.org BRI s major contributions to type 1 diabetes research Identified type 1 diabetes susceptibility

More information

Stella Jacobson. Thesis for doctoral degree (Ph.D.) 2010

Stella Jacobson. Thesis for doctoral degree (Ph.D.) 2010 Thesis for doctoral degree (Ph.D.) 2010 Thesis for doctoral degree (Ph.D.) 2010 TYPE 1 DIABETES - THE AUTOIMMUNE PROCESS AND ISLET TRANSPLANTATION Stella Jacobson TYPE 1 DIABETES - THE AUTOIMMUNE PROCESS

More information

Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT

Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT Role of NMDP Repository in the Evolution of HLA Matching and Typing for Unrelated Donor HCT Stephen Spellman, MBS Director, Immunobiology and Observational Research Assistant Scientific Director CIBMTR,

More information

HLA Mismatches. Professor Steven GE Marsh. Anthony Nolan Research Institute EBMT Anthony Nolan Research Institute

HLA Mismatches. Professor Steven GE Marsh. Anthony Nolan Research Institute EBMT Anthony Nolan Research Institute HLA Mismatches Professor Steven GE Marsh HLA Mismatches HLA Genes, Structure, Polymorphism HLA Nomenclature HLA Mismatches in HSCT Defining a mismatch HLA Mismatches HLA Genes, Structure, Polymorphism

More information

B F. Location of MHC class I pockets termed B and F that bind P2 and P9 amino acid side chains of the peptide

B F. Location of MHC class I pockets termed B and F that bind P2 and P9 amino acid side chains of the peptide Different MHC alleles confer different functional properties on the adaptive immune system by specifying molecules that have different peptide binding abilities Location of MHC class I pockets termed B

More information

Key words: antiphospholipid syndrome, trombosis, pathogenesis

Key words: antiphospholipid syndrome, trombosis, pathogenesis 26. XI,. 4/2011,.,..,..,., -..,,. 2GPI. -,.,,., -,, -, -,,,,, IL-1, IL-2, IL-6, IL-8, IL-12, IL-10, TNF, INF-. :,, N. Stoilov, R. Rashkov and R. Stoilov. ANTIPHOSPHOLIPID SYNDROME HISTORICAL DATA, ETI-

More information

T-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes:

T-cell activation T cells migrate to secondary lymphoid tissues where they interact with antigen, antigen-presenting cells, and other lymphocytes: Interactions between innate immunity & adaptive immunity What happens to T cells after they leave the thymus? Naïve T cells exit the thymus and enter the bloodstream. If they remain in the bloodstream,

More information

Humoral Autoimmunity in Type 1 Diabetes: Prediction, Significance, and Detection of Distinct Disease Subtypes

Humoral Autoimmunity in Type 1 Diabetes: Prediction, Significance, and Detection of Distinct Disease Subtypes Humoral Autoimmunity in Type 1 Diabetes: Prediction, Significance, and Detection of Distinct Disease Subtypes Massimo Pietropaolo 1, Roberto Towns 1, and George S. Eisenbarth 2 1 Laboratory of Immunogenetics,

More information

Diabetes Mellitus in the Pediatric Patient

Diabetes Mellitus in the Pediatric Patient Diabetes Mellitus in the Pediatric Patient William Bryant, M.D. Chief of Section Pediatric Endocrinology Children s Hospital at Scott & White Texas A&M University Temple, Texas Disclosures None Definitions

More information

Antigen Presentation to T lymphocytes

Antigen Presentation to T lymphocytes Antigen Presentation to T lymphocytes Immunology 441 Lectures 6 & 7 Chapter 6 October 10 & 12, 2016 Jessica Hamerman jhamerman@benaroyaresearch.org Office hours by arrangement Antibodies and T cell receptors

More information

Diabetes In Somali Children In Minneapolis and St.Paul, Minnesota

Diabetes In Somali Children In Minneapolis and St.Paul, Minnesota Diabetes In Somali Children In Minneapolis and St.Paul, Minnesota A Thesis SUBMITTED TO THE FACULTY OF UNIVERSITY OF MINNESOTA BY Muna S Sunni, MBBCh IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE

More information

Zinc transporter 8 autoantibodies are a risk factor for type 1 diabetes recurrence in recipients of simultaneous pancreas kidney transplants

Zinc transporter 8 autoantibodies are a risk factor for type 1 diabetes recurrence in recipients of simultaneous pancreas kidney transplants University of Ulm Department of Pediatrics and Adolescent Medicine Chairman: Prof. Dr. med. Klaus-Michael Debatin Division of Pediatric Endocrinology and Diabetes Head: Prof. Dr. med. Martin Wabitsch Zinc

More information

MHC class I MHC class II Structure of MHC antigens:

MHC class I MHC class II Structure of MHC antigens: MHC class I MHC class II Structure of MHC antigens: MHC class I antigens consist of a transmembrane heavy chain (α chain) that is non-covalently associated with β2- microglobulin. Membrane proximal domain

More information

How to Find an Unrelated Donor Theory & Technology

How to Find an Unrelated Donor Theory & Technology How to Find an Unrelated Donor Theory & Technology Carlheinz R. Müller Zentrales Knochenmarkspender-Register für die Bundesrepublik Deutschland (ZKRD) Ulm, Germany How to Find an Unrelated Donor HLA-Basics

More information

Immunology - Lecture 2 Adaptive Immune System 1

Immunology - Lecture 2 Adaptive Immune System 1 Immunology - Lecture 2 Adaptive Immune System 1 Book chapters: Molecules of the Adaptive Immunity 6 Adaptive Cells and Organs 7 Generation of Immune Diversity Lymphocyte Antigen Receptors - 8 CD markers

More information

Ray A. Kroc & Robert L. Kroc. BDC Lectureship 2014

Ray A. Kroc & Robert L. Kroc. BDC Lectureship 2014 Ray A. Kroc & Robert L. Kroc BDC Lectureship 2014 Ray Kroc (Big Mack) 1902-1984 Predominant establisher of the McDonald's Corporation (1961) Philanthropist: Research and treatment of alcoholism, diabetes,

More information

1. PATHOPHYSIOLOGY OF DIABETES MELLITUS

1. PATHOPHYSIOLOGY OF DIABETES MELLITUS 1. PATHOPHYSIOLOGY OF DIABETES MELLITUS Prof. Vladimir Palicka, M.D., Ph.D. Institute for Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic Diabetes mellitus is

More information

[AUTOIMMUNITY] July 14, 2013

[AUTOIMMUNITY] July 14, 2013 This sheet includes only the extra notes. Slide 5,6: [AUTOIMMUNITY] July 14, 2013 Autoimmunity is the condition or case where the immune system is activated by self antigensand when the immune system no

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow. Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature

More information

Chapter 7: Pedigree Analysis B I O L O G Y

Chapter 7: Pedigree Analysis B I O L O G Y Name Date Period Chapter 7: Pedigree Analysis B I O L O G Y Introduction: A pedigree is a diagram of family relationships that uses symbols to represent people and lines to represent genetic relationships.

More information

ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease

ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease (2006) 7, 550 554 & 2006 Nature Publishing Group All rights reserved 1466-4879/06 $30.00 www.nature.com/gene ORIGINAL ARTICLE Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients

More information

Alleles: the alternative forms of a gene found in different individuals. Allotypes or allomorphs: the different protein forms encoded by alleles

Alleles: the alternative forms of a gene found in different individuals. Allotypes or allomorphs: the different protein forms encoded by alleles Nomenclature Alleles: the alternative forms of a gene found in different individuals Allotypes or allomorphs: the different protein forms encoded by alleles Genotype: the collection of genes in an individual,

More information

Diabetes overview and classification

Diabetes overview and classification Diabetes overview and classification Polly Bingley Why classify diabetes? Guide immediate management Inform prognosis Reduce risk of diabetic emergencies Ensure curable causes are not missed Summary ADA/WHO

More information

How T cells recognize antigen. How T cells recognize antigen -concepts

How T cells recognize antigen. How T cells recognize antigen -concepts Adaptive immunity How T cells recognize antigen Starting point: 2. Diversity in antigen recognition is accomplished, in part, by rearrangements in the TCR loci. This occurs in the thymus 3. The T cell

More information

Lecture 1 Mendelian Inheritance

Lecture 1 Mendelian Inheritance Genes Mendelian Inheritance Lecture 1 Mendelian Inheritance Jurg Ott Gregor Mendel, monk in a monastery in Brünn (now Brno in Czech Republic): Breeding experiments with the garden pea: Flower color and

More information

Autoantibodies in Diabetes

Autoantibodies in Diabetes Autoantibodies in Diabetes Catherine Pihoker, Lisa K. Gilliam, Christiane S. Hampe, and Åke Lernmark Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance

More information

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow.

Chapter 11. B cell generation, Activation, and Differentiation. Pro-B cells. - B cells mature in the bone marrow. Chapter B cell generation, Activation, and Differentiation - B cells mature in the bone marrow. - B cells proceed through a number of distinct maturational stages: ) Pro-B cell ) Pre-B cell ) Immature

More information

Abstract. Keywords Type 1 diabetes, HLA-DQB1, Autoantibody, Finland, General population, Risk group.

Abstract. Keywords Type 1 diabetes, HLA-DQB1, Autoantibody, Finland, General population, Risk group. Diabetologia (2003) 46:65 70 DOI 10.1007/s00125-002-0976-5 Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction

More information

Prediction and Pathogenesis in Type 1 Diabetes

Prediction and Pathogenesis in Type 1 Diabetes Prediction and Pathogenesis in Type 1 Diabetes Anette-G. Ziegler 1, * and Gerald T. Nepom 2, * 1 Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804

More information

Lecture 13: May 24, 2004

Lecture 13: May 24, 2004 Lecture 13: May 24, 2004 CH14: Mendel and the gene idea *particulate inheritance parents pass on discrete heritable units *gene- unit of inheritance which occupies a specific chromosomal location (locus)

More information

Graves' disease and HLA association

Graves' disease and HLA association ISSN: 2319-7706 Volume 3 Number 1 (2014) pp. 155-159 http://www.ijcmas.com Review Article Graves' disease and HLA association Batool Mutar Mahdi* Director of HLA Typing Research Unit, Depatment of Microbiology,

More information

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes Received: 28 September 2016 Revised: 26 June 2017 Accepted: 10 July 2017 DOI: 10.1002/dmrr.2921 RESEARCH ARTICLE Building and validating a prediction model for paediatric type 1 diabetes risk using next

More information

Altering The Course Of Type 1 Diabetes

Altering The Course Of Type 1 Diabetes Altering The Course Of Type 1 Diabetes JDRF TypeOneNation Summit 09.18.16 Stephen E. Gitelman, MD UCSF sgitelma@.ucsf.edu Today s Agenda My story The path to Type 1 Diabetes Prevention efforts New-onset

More information

Immunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters,

Immunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, Immunology T-Lymphocytes 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, karin.peters@rub.de The role of T-effector cells in the immune response against microbes cellular immunity humoral immunity

More information

Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype

Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype Research: Genetics HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotype J. M. M. Howson 1,2, M. S. Roy 3, L. Zeitels 1, H. Stevens 1 and J. A. Todd

More information

Genetic and mechanism-based therapeutic approaches to treat human autoimmune diseases

Genetic and mechanism-based therapeutic approaches to treat human autoimmune diseases Genetic and mechanism-based therapeutic approaches to treat human autoimmune diseases Professor John Todd FRS PhD Director, JDRF/WT Diabetes & Inflammation Laboratory NIHR Cambridge Biomedical Research

More information

Fetal-Maternal HLA Relationships and Autoimmune Disease. Giovanna Ibeth Cruz. A dissertation submitted in partial satisfaction of the

Fetal-Maternal HLA Relationships and Autoimmune Disease. Giovanna Ibeth Cruz. A dissertation submitted in partial satisfaction of the Fetal-Maternal HLA Relationships and Autoimmune Disease By Giovanna Ibeth Cruz A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Epidemiology

More information

IMMUNOBIOLOGY OF TRANSPLANTATION. Wasim Dar

IMMUNOBIOLOGY OF TRANSPLANTATION. Wasim Dar IMMUNOBIOLOGY OF TRANSPLANTATION Wasim Dar Immunobiology of Transplantation Overview Transplantation: A complex immunologic process Contributions Innate Immunity Adaptive immunity T Cells B Cells HLA Consequences

More information

Adaptive Immunity: Specific Defenses of the Host

Adaptive Immunity: Specific Defenses of the Host 17 Adaptive Immunity: Specific Defenses of the Host SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function

More information

SEVENTH EDITION CHAPTER

SEVENTH EDITION CHAPTER Judy Owen Jenni Punt Sharon Stranford Kuby Immunology SEVENTH EDITION CHAPTER 16 Tolerance, Autoimmunity, and Transplantation Copyright 2013 by W. H. Freeman and Company Immune tolerance: history * Some

More information

The Adaptive Immune Response. T-cells

The Adaptive Immune Response. T-cells The Adaptive Immune Response T-cells T Lymphocytes T lymphocytes develop from precursors in the thymus. Mature T cells are found in the blood, where they constitute 60% to 70% of lymphocytes, and in T-cell

More information

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder)

Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) Genetics and Pharmacogenetics in Human Complex Disorders (Example of Bipolar Disorder) September 14, 2012 Chun Xu M.D, M.Sc, Ph.D. Assistant professor Texas Tech University Health Sciences Center Paul

More information

MHC Class II. Alexandra López Laura Taberner Gemma Vilajosana Ilia Villate. Structural Biology Academic year Universitat Pompeu Fabra

MHC Class II. Alexandra López Laura Taberner Gemma Vilajosana Ilia Villate. Structural Biology Academic year Universitat Pompeu Fabra MHC Class II Alexandra López Laura Taberner Gemma Vilajosana Ilia Villate Structural Biology Academic year 2012-2013 Universitat Pompeu Fabra Index - Introduction - Peptide binding to MHC class II - pockets

More information

CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic and -extrinsic mechanisms

CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic and -extrinsic mechanisms Class 15, BBS821: Control of pathogenic self-reactive T cells by co-inhibitory molecules, J. Kang Oct 29, 2015 CTLA-4 regulates pathogenicity of antigen-specific autoreactive T cells by cell-intrinsic

More information

HLA Selected Platelets

HLA Selected Platelets HLA Selected Platelets Dr PhD Clinical Scientist Department of Histocompatibility & Immunogenetics NHS Blood and Transplant Colindale Poor increment (

More information

MULTIFACTORIAL DISEASES. MG L-10 July 7 th 2014

MULTIFACTORIAL DISEASES. MG L-10 July 7 th 2014 MULTIFACTORIAL DISEASES MG L-10 July 7 th 2014 Genetic Diseases Unifactorial Chromosomal Multifactorial AD Numerical AR Structural X-linked Microdeletions Mitochondrial Spectrum of Alterations in DNA Sequence

More information

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Prepared

More information

IMMUNITY AND DISEASE II

IMMUNITY AND DISEASE II IMMUNITY AND DISEASE II A. Evolution of the immune system. 1. Figure 1--57.25, p. 1167 from Raven and Johnson Biology 6 th ed. shows how the immune system evolved. Figure 1. How the immune system evolved.

More information

GENETIC SIMILARITIES BETWEEN LADA, TYPE 1 AND TYPE 2 DIABETES

GENETIC SIMILARITIES BETWEEN LADA, TYPE 1 AND TYPE 2 DIABETES Diabetes Publish Ahead of Print, published online March 13, 2008 GENETIC SIMILARITIES BETWEEN LADA, TYPE 1 AND TYPE 2 DIABETES Camilla Cervin 1, Valeriya Lyssenko 1, Ekaterine Bakhtadze 1, Eero Lindholm

More information

Islet Cell Autoantibodies in Cord Blood from Children with Blood Group Incompatibility or Hyperbilirubinemia

Islet Cell Autoantibodies in Cord Blood from Children with Blood Group Incompatibility or Hyperbilirubinemia Autoimmunity, 2003 Vol. 36 (2), pp. 111 115 Islet Cell Autoantibodies in Cord Blood from Children with Blood Group Incompatibility or Hyperbilirubinemia A. MARIA ELFVING a, BENGT A. LINDBERG b, *, M. LANDIN-OLSSON

More information

Chapter 35 Active Reading Guide The Immune System

Chapter 35 Active Reading Guide The Immune System Name: AP Biology Mr. Croft Chapter 35 Active Reading Guide The Immune System Section 1 Phagocytosis plays an important role in the immune systems of both invertebrates and vertebrates. Review the process

More information

MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy

MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy Zhao Cui,* Li-jun Xie,* Fang-jin Chen, Zhi-yong Pei, Li-jie Zhang, Zhen Qu,* Jing Huang,* Qiu-hua Gu,* Yi-miao Zhang,*

More information

A second type of TCR TCR: An αβ heterodimer

A second type of TCR TCR: An αβ heterodimer How s recognize antigen: The T Cell Receptor (TCR) Identifying the TCR: Why was it so hard to do By the early 1980s, much about function was known, but the receptor genes had not been identified Recall

More information

Complex Multifactorial Genetic Diseases

Complex Multifactorial Genetic Diseases Complex Multifactorial Genetic Diseases Nicola J Camp, University of Utah, Utah, USA Aruna Bansal, University of Utah, Utah, USA Secondary article Article Contents. Introduction. Continuous Variation.

More information

Effector T Cells and

Effector T Cells and 1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New

More information

The Basics: A general review of molecular biology:

The Basics: A general review of molecular biology: The Basics: A general review of molecular biology: DNA Transcription RNA Translation Proteins DNA (deoxy-ribonucleic acid) is the genetic material It is an informational super polymer -think of it as the

More information

Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients 6,7

Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients 6,7 Pathophysiology/Complications O R I G I N A L A R T I C L E Identification of Autoantibody-Negative Autoimmune Type 2 Diabetic Patients BARBARA M. BROOKS-WORRELL, PHD 1,2,3,4 JESSICA L. REICHOW, BS 3 AMIT

More information

A gene is a sequence of DNA that resides at a particular site on a chromosome the locus (plural loci). Genetic linkage of genes on a single

A gene is a sequence of DNA that resides at a particular site on a chromosome the locus (plural loci). Genetic linkage of genes on a single 8.3 A gene is a sequence of DNA that resides at a particular site on a chromosome the locus (plural loci). Genetic linkage of genes on a single chromosome can alter their pattern of inheritance from those

More information

PREIMPLANTATION GENETIC DIAGnosis

PREIMPLANTATION GENETIC DIAGnosis ORIGINAL CONTRIBUTION Preimplantation HLA Testing Yury Verlinsky, PhD Svetlana Rechitsky, PhD Tatyana Sharapova, MS Randy Morris, MD Mohammed Taranissi, MD Anver Kuliev, MD, PhD For editorial comment see

More information

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country The new england journal of medicine original article Risk of Pediatric Celiac Disease According to HLA Haplotype and Country Edwin Liu, M.D., Hye-Seung Lee, Ph.D., Carin A. Aronsson, M.Sc., William A.

More information

Amino Acids. Amino Acids. Fundamentals. While their name implies that amino acids are compounds that contain an NH. 3 and CO NH 3

Amino Acids. Amino Acids. Fundamentals. While their name implies that amino acids are compounds that contain an NH. 3 and CO NH 3 Fundamentals While their name implies that amino acids are compounds that contain an 2 group and a 2 group, these groups are actually present as 3 and 2 respectively. They are classified as α, β, γ, etc..

More information

Class XII Chapter 5 Principles of Inheritance and Variation Biology

Class XII Chapter 5 Principles of Inheritance and Variation Biology Question 1: Mention the advantages of selecting pea plant for experiment by Mendel. Mendel selected pea plants to carry out his study on the inheritance of characters from parents to offspring. He selected

More information

B-4.7 Summarize the chromosome theory of inheritance and relate that theory to Gregor Mendel s principles of genetics

B-4.7 Summarize the chromosome theory of inheritance and relate that theory to Gregor Mendel s principles of genetics B-4.7 Summarize the chromosome theory of inheritance and relate that theory to Gregor Mendel s principles of genetics The Chromosome theory of inheritance is a basic principle in biology that states genes

More information

Pedigree Analysis Why do Pedigrees? Goals of Pedigree Analysis Basic Symbols More Symbols Y-Linked Inheritance

Pedigree Analysis Why do Pedigrees? Goals of Pedigree Analysis Basic Symbols More Symbols Y-Linked Inheritance Pedigree Analysis Why do Pedigrees? Punnett squares and chi-square tests work well for organisms that have large numbers of offspring and controlled mating, but humans are quite different: Small families.

More information

Prevention of type 1 diabetes by gene therapy

Prevention of type 1 diabetes by gene therapy Related Commentary, page 892 Research article Prevention of type 1 diabetes by gene therapy Chaorui Tian, 1 Jessamyn Bagley, 1 Nathalie Cretin, 1 Nilufer Seth, 2 Kai W. Wucherpfennig, 2 and John Iacomini

More information

Examples of questions for Cellular Immunology/Cellular Biology and Immunology

Examples of questions for Cellular Immunology/Cellular Biology and Immunology Examples of questions for Cellular Immunology/Cellular Biology and Immunology Each student gets a set of 6 questions, so that each set contains different types of questions and that the set of questions

More information

Treatment of Chronic Antibody Mediated Rejection

Treatment of Chronic Antibody Mediated Rejection Treatment of Chronic Antibody Mediated Rejection Robert A. Montgomery MD, DPhil Professor of Surgery Director of the NYU Langone Transplant Institute Disclosures: Served on Advisory Boards for Genentech

More information