Control of Immune Responses by Regulatory T Cells. Dr Lucy Walker University of Birmingham

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Control of Immune Responses by Regulatory T Cells. Dr Lucy Walker University of Birmingham"

Transcription

1 Control of Immune Responses by Regulatory T Cells Dr Lucy Walker University of Birmingham

2 What are Regulatory T cells? T cells which can negatively regulate immune responses (prevent autoimmunity) There are likely to be many different types: most well characterised is the natural Treg that is derived from the thymus and is a CD4+CD25+ T cell. CD4+ CD25+ There are also adaptive Treg : these are conventional T cells that are induced to turn into Treg in the periphery will cover these briefly towards end of lecture

3 History of Treg 1970 s/80 s Existence of Suppressor T cells proposed. Some data flawed. Idea became discredited. Mid 1990 s Re-birth of the idea of suppressor cells. This time termed Regulatory T cells. The work of Shimon Sakaguchi was particularly important (also Ethan Shevach and Fiona Powrie). Present Enormous research interest in Treg. Thought to have significant clinical potential.

4 Natural CD4+CD25+ Treg CD4+ CD25+ Generated in the thymus Treg Express CD25 (the IL-2 Receptor alpha chain). Note: this is also expressed by activated T cells CD25 CD4 Constitute 5-10% of peripheral CD4 T cells Conventional T cells Can suppress multiple cell types: CD4, CD8 T cells, B cells?, innate immune system

5 Treg Phenotype Express CTLA-4. % of Max CD4 + Foxp3 - Tconv CD4 + Foxp3 + Tregs Intracellular CTLA-4 Express low levels of the CD127 (IL-7 receptor) (particularly important in phenotyping of human Treg) Are anergic in vitro Fail to proliferate following TCR stimulation in vitro. Also fail to make IL-2. Express the transcription factor FOXP3 (involved in Treg differentiation)

6 FOXP3: the masterswitch for Treg differentiation? A transcription factor with a forkhead domain Foxp3 is expressed in CD4+CD25+ cells [Fontenot et al (2003) 4:304] Foxp3 deficient mice: CD4 T cell-dependent lymphoproliferative disease, wasting. T cells are activated and proliferate spontaneously [Clark et al JI :2546] QuickTime and a TIFF (LZW) decompressor are needed to see this picture. Targets of Foxp3? Foxp3 reinforces the Treg phenotype Directly binds to CD25 and CTLA-4 promoters Represses alternative T cell differentiation fates [Zheng et al (2007) 445:936-40] [Gavin et al (2007) 445:771-5] Foxp3- (scurfy) Wildtype Foxp3- plus wildtype CD4+CD25+ cells

7 IPEX: a human syndrome characterised by mutations in Foxp3 Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome Rare recessive disorder - aggressive autoimmunity + early death >80% IPEX patients have Type 1 diabetes (also IBD, allergy) QuickTime and a TIFF (LZW) decompressor are needed to see this picture. [Wildin et al J Med Gen :537]

8 Natural Treg CD4+ CD25+ Produced in the thymus Express CD25 (IL-2 receptor alpha chain) and CTLA-4 Express the transcription factor Foxp3 Experimental Evidence?

9 Pioneering Treg work of mid 1990s Sakaguchi Lab: Asano et al. (1996). JEM 184: Mice lacking thymus (nude) Reconstitute with. Outcome Total T cells Healthy CD25-depleted T cells Autoimmunity (Gastritis, Oophoritis, Thyroiditis) Our own T cells are dangerous unless kept in check by CD25+ Treg!!

10 QuickTime and a TIFF (LZW) decompressor are needed to see this picture. How are natural Treg born? Treg differentiation in the thymus is influenced by: TCR ligand CD28 signals What determines deletion versus Treg selection? DO11 DO11 x RIP-OVA CD25 and a mpressor is picture. CD4 TCR TCR + antigen in thymus Treg differentiation doesn t require a dedicated antigen-presenting cell [Liston et al PNAS :11903] [Wirnsberger et al PNAS :10278] but may be limited by the availability of peptide-mhc complexes [Bautista et al Nat Immunol :610]

11 How do Treg work? Is suppression antigen-specific? Does suppression require cytokines? Does suppression require CTLA-4? Does suppression involve modulating the antigen-presenting cell?

12 Is suppression antigen-specific? CD25- CD25+ TCR A TCR B APC Can a Treg specific for one peptide control a naïve T cell specific for a different peptide?

13 Is suppression antigen-specific? Peptide A 25+ TCR A 25- TCR A + APC suppression Peptide B 25+ TCR A 25- TCR B + APC No Suppression (Treg has no ligand) Peptide A Peptide B 25+ TCR A 25- TCR B + APC suppression [Thornton et al J Immunol (2000) 164:183-90]

14 Treg need to be activated through their TCR to acquire suppressive function. Induction of suppressive activity in Treg is antigen-dependent BUT Once, activated, they can then suppress T cells bearing different specificities. Effector function of Treg is NOT antigen-specific

15 Is suppression antigen-specific? Does suppression require cytokines? Does suppression require CTLA-4? Does suppression involve modulating the antigen-presenting cell?

16 Treg aren t able to control colitis in presence of blocking TGFbeta antibodies [Powrie et al JEM (1996) 183: ] CD8 T cells that can t receive TGFbeta signals can t be suppressed in a diabetes model [Green et al PNAS (2003) 100: ] TGFbeta not required in all models of suppression

17 Treg aren t able to control colitis in presence of blocking IL-10 antibodies [Asseman et al JEM (1999) 190: ] Mice in which Treg can t make IL-10, don t look like Foxp3-null mice Implies IL-10 doesn t account for all Treg function [Rubtsov et al Immunity (2008) 28:546-58] Effector cell IL-10-/- Treg Effector cell Treg Perhaps the requirement for IL-10 depends on what is being regulated? IL-10 is needed for Treg control of colitis induced by antigen-experienced T cells, but is dispensible for control of colitis induced by naïve T cells [Asseman et al J Immunol (2003) 171:971-8]

18 Made up of the Epstein-Barr-virus-induced gene 3 (Ebi3) paired with IL-12α IL-35 = Ebi3 + IL-12α (Ebi3 is the IL-27β chain - it can also pair with IL-27α to form the cytokine IL-27) IL-27 = Ebi3 + IL27α Treg express both Ebi3 and IL-12α and it has been suggested that Tregs from Ebi3-/- mice are less suppressive. Expression of IL-35 in T cells can confer regulatory activity. [Collinson LW et al Nature 450:566-9 (2007)] [Niedbala W et al Eur.J. Immunol. 37: (2007)] The extent to which IL-35 forms naturally is unclear The role of IL-35 in Treg suppression is controversial... [Bardel E et al J Immunol 181: (2008)]

19 Is suppression antigen-specific? Does suppression require cytokines? Does suppression require CTLA-4? Does suppression involve modulating the antigen-presenting cell? CTLA-4 CD28 CD86/80 T cell TCR MHC CD40L CD40 APC

20 Ctla-4-/- CTLA-4-/- mice die of autoimmune lymphoproliferative syndrome (like Foxp3-null mice) Control Ctla-4-/- Treg CTLA-4-/- Is this because CTLA-4 is needed for Treg to work? What if you knock out CTLA-4 just in Treg? Effector cell Mouse gets lethal lymphoproliferative disease! Only lives a few weeks longer than a mouse lacking CTLA-4 everywhere (not just in Treg) Wing et al (2008) Science 322:271-5

21 Role for CTLA-4 in Treg Function? Adoptive transfer mouse model of diabetes OVA-specific T cells OVA in pancreas Diabetes OVA-specific Treg (what if Treg are CTLA-4 deficient?)

22 Can antigen-specific CTLA-4-/- Treg protect from diabetes? CD25- alone CD25- plus wt CD25+ CD25- plus ct-/- CD Days post Transfer CTLA-4-/- Treg don t! Normal Treg protect [Schmidt et al (2009) J Immunol, 182:274-82] Suggests CTLA-4 expression important for Treg function, at least in some settings

23 Is suppression antigen-specific? Does suppression require cytokines? Does suppression require CTLA-4? Does suppression involve modulating the antigen-presenting cell?

24 Does suppression involve modifying the Antigen Presenting Cell? Treg inhibits APC CD25+ CD25- APC APC loses its stimulatory capacity ie. Effect of Treg on naïve responder T cells could be indirect

25 Treg may alter antigen presenting cells Treg may influence expression of costimulatory ligands on dendritic cells [Cederbom EJI 2003] Treg may influence dendritic cell maturation [Sakaguchi EJI 2003] QuickTime and a TIFF (LZW) decompressor are needed to see this picture. Treg can also alter phenotype of macrophages [Tiemessen et al (2007) PNAS 104: ]

26 Other proposed mechanisms of Treg Function [Vignali et al Nat Rev Immunol (2008) 8:523-32] very controversial! QuickTime and a TIFF (LZW) decompressor are needed to see this picture. Competition (for cytokines, APC, space) Granzyme B-mediated apoptosis CD39 or CD73-generated adenosine etc

27 Clinical Relevance of Treg Biology Autoimmunity Cancer Transplantation Infection

28 Autoimmunity Treg defects may underlie certain autoimmune conditions (Autoimmune polyglandular syndrome Type II) T cells may be resistant to Treg control (SLE) Cancer Depletion of CD25+ cells can enhance anti-tumour responses. [Shimizu et al (1999) J.Immunol 163:5211-8] Implies that Treg may regulate immuno-surveillance to tumour antigens

29 Transplantation In a model of transplantation tolerance, the CD25+ cells are the ones responsible for tolerance induction. [Hara et al (2001) J.Immunol 166: ] Role of Treg in transplantation tolerance = extremely active area of research Infection Depletion of CD25+ cells can enhance responses to infectious agents eg Leishmania major. [Aseffa et al (2002) J.Immunol 169: ]

30 Adaptive Treg Treg (CD4+Foxp3+) can be readily induced in vitro from naïve CD4+ T cells - e.g. by culture with TGFβ Treg may be induced in vivo at specialised sites Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. [Sun et al J Exp Med (2007) 204: ] Priming conditions can control whether a mature CD4+ T cell differentiates into a pathogenic cell (IL-17) or regulatory cell (Foxp3) [Veldhoen et al Immunity (2006) 24:179-89] [Bettelli et al Nature (2006) 441:1235-8] = very topical and exciting area

31 Future Treg suppressive mechanisms - which ones when and where? Stability of Treg? Fixed lineage or plastic? Specialisation of Treg (Expression of transcription factors normally associated with effector T cells eg.tbet) Clinical exploitation of our knowledge of Treg

The immune system. Bone marrow. Thymus. Spleen. Bone marrow. NK cell. B-cell. T-cell. Basophil Neutrophil. Eosinophil. Myeloid progenitor

The immune system. Bone marrow. Thymus. Spleen. Bone marrow. NK cell. B-cell. T-cell. Basophil Neutrophil. Eosinophil. Myeloid progenitor The immune system Basophil Neutrophil Bone marrow Eosinophil Myeloid progenitor Dendritic cell Pluripotent Stem cell Lymphoid progenitor Platelets Bone marrow Thymus NK cell T-cell B-cell Spleen Cancer

More information

Lecture 8: The Development and Survival of Lymphocytes (based on lecture by Dr. Barbara Birshtein)

Lecture 8: The Development and Survival of Lymphocytes (based on lecture by Dr. Barbara Birshtein) Lecture 8: The Development and Survival of Lymphocytes (based on lecture by Dr. Barbara Birshtein) Questions to Consider How does the immune system provide a high degree of sensitivity and specificity

More information

CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES

CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES An understanding of the distinct families of molecules present on different cells of the immune system provides the tools for distinguishing

More information

Chapter 17A: Adaptive Immunity Part I

Chapter 17A: Adaptive Immunity Part I Chapter 17A: Adaptive Immunity Part I 1. Overview of Adaptive Immunity 2. T and B Cell Production 3. Antigens & Antigen Presentation 4. Helper T cells 1. Overview of Adaptive Immunity The Nature of Adaptive

More information

Micro 204 Tumor Immunology.

Micro 204 Tumor Immunology. Micro 204 Tumor Immunology Lewis.Lanier@ucsf.edu Immunological Surveillance Ehrlich, Burnet & Thomas Paul Ehrlich (1909) Concept of cancer immunosurveillance. Predicted that cancer would occur at incredible

More information

Autoimmunity and immunemediated. FOCiS. Lecture outline

Autoimmunity and immunemediated. FOCiS. Lecture outline 1 Autoimmunity and immunemediated inflammatory diseases Abul K. Abbas, MD UCSF FOCiS 2 Lecture outline Pathogenesis of autoimmunity: why selftolerance fails Genetics of autoimmune diseases Therapeutic

More information

Vitamin D deficiency exacerbates ischemic cell loss and sensory motor dysfunction in an experimental stroke model

Vitamin D deficiency exacerbates ischemic cell loss and sensory motor dysfunction in an experimental stroke model Vitamin D deficiency exacerbates ischemic cell loss and sensory motor dysfunction in an experimental stroke model Robyn Balden & Farida Sohrabji Texas A&M Health Science Center- College of Medicine ISC

More information

The Most Common Autoimmune Disease: Rheumatoid Arthritis. Bonita S. Libman, M.D.

The Most Common Autoimmune Disease: Rheumatoid Arthritis. Bonita S. Libman, M.D. The Most Common Autoimmune Disease: Rheumatoid Arthritis Bonita S. Libman, M.D. Disclosures Two googled comics The Normal Immune System Network of cells and proteins that work together Goal: protect against

More information

99 學年度中醫系免疫學第二次期中考. Dr. Hsi-Hsien Lin (40%) I. Terminology: (12 %) 1. Immunoproteasome 2. ITAM. 3. Invariant chain. 4. Anchor residues 5.

99 學年度中醫系免疫學第二次期中考. Dr. Hsi-Hsien Lin (40%) I. Terminology: (12 %) 1. Immunoproteasome 2. ITAM. 3. Invariant chain. 4. Anchor residues 5. 99 學年度中醫系免疫學第二次期中考 學號 姓名 Dr. Hsi-Hsien Lin (40%) I. Terminology: (12 %) 1. Immunoproteasome 2. ITAM 3. Invariant chain 4. Anchor residues 5. SMAC 6. Cross-presentation of Ag II. Single Choice (12%). Please

More information

Cancer Immunotherapy: Can Your Immune System Cure Cancer? Steve Emerson, MD, PhD Herbert Irving Comprehensive Cancer Center

Cancer Immunotherapy: Can Your Immune System Cure Cancer? Steve Emerson, MD, PhD Herbert Irving Comprehensive Cancer Center Cancer Immunotherapy: Can Your Immune System Cure Cancer? Steve Emerson, MD, PhD Herbert Irving Comprehensive Cancer Center Bodnar s Law Simple Things are Important Very Simple Things are Very Important

More information

Chapter 22: The Lymphatic System and Immunity

Chapter 22: The Lymphatic System and Immunity Chapter 22: The Lymphatic System and Immunity Introduction Immune system the body s defenses against pathogens that produce disease 2 types of immunity Nonspecific immune mechanisms (Innate immunity) Provide

More information

specific B cells Humoral immunity lymphocytes antibodies B cells bone marrow Cell-mediated immunity: T cells antibodies proteins

specific B cells Humoral immunity lymphocytes antibodies B cells bone marrow Cell-mediated immunity: T cells antibodies proteins Adaptive Immunity Chapter 17: Adaptive (specific) Immunity Bio 139 Dr. Amy Rogers Host defenses that are specific to a particular infectious agent Can be innate or genetic for humans as a group: most microbes

More information

Adaptive Immunity in Organ Transplantation

Adaptive Immunity in Organ Transplantation Adaptive Immunity in Organ Transplantation Rainer Krebs Transplantation Laboratory Cardiopulmonary Research Group 12-02-2014 Adaptive vs innate immunity INNATE immunity: first line of defense quick reaction,

More information

and Antigen Presentation

and Antigen Presentation 1 Innate Immunity and Antigen Presentation Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Innate immunity Receptors and mechanisms Roles in disease Antigen

More information

IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM

IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM 59 IMMUNOLOGY STRUCTURE AND FUNCTION OF IMMUNE SYSTEM 59.1 INTRODUCTION The immune system is engaged in a constant surveillance of the body for pathogens or tumors. Whether disease develops depends on

More information

B Cells and Antibodies

B Cells and Antibodies B Cells and Antibodies Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School Lecture outline Functions of antibodies B cell activation; the role of helper T cells in antibody production

More information

T cell maturation. T-cell Maturation. What allows T cell maturation?

T 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 information

Dendritic Cells: A Basic Review *last updated May 2003

Dendritic Cells: A Basic Review *last updated May 2003 *last updated May 2003 Prepared by: Eric Wieder, PhD MD Anderson Cancer Center Houston, TX USA What is a dendritic cell? Dendritic cells are antigen-presenting cells (APCs) which play a critical role in

More information

T Cell Maturation,Activation and Differentiation

T Cell Maturation,Activation and Differentiation T Cell Maturation,Activation and Differentiation Positive Selection- In thymus, permits survival of only those T cells whose TCRs recognize self- MHC molecules (self-mhc restriction) Negative Selection-

More information

The Adaptive Immune System

The Adaptive Immune System Chapter 17 Functional Anatomy of Prokaryotic and Eukaryotic Cells Lectures prepared by Christine L. Case The Adaptive Immune System Learning Objectives 17-1 Differentiate innate from adaptive immunity.

More information

THE IMMUNOLOGICAL BASIS FOR AUTOIMMUNITY Sita Naik Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow

THE IMMUNOLOGICAL BASIS FOR AUTOIMMUNITY Sita Naik Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow Immunology for clinicians J Indian Rheumatol Assoc 2004 : 12 : 22-28 THE IMMUNOLOGICAL BASIS FOR AUTOIMMUNITY Sita Naik Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,

More information

FARMACOLOGIA DEL SISTEMA INMUNE

FARMACOLOGIA DEL SISTEMA INMUNE FARMACOLOGIA DEL SISTEMA INMUNE Inmunosupresión Inmunoestimulación Medicina Molecular. JM,2008 Las dos caras de Janus INMUNOSUPRESIÓN CICLOSPORINA Jean Francois Borel Scanning electron micrograph of

More information

B cell activation and Humoral Immunity

B cell activation and Humoral Immunity B cell activation and Humoral Immunity Humoral immunity is mediated by secreted antibodies and its physiological function is defense against extracellular microbes (including viruses) and microbial exotoxins.

More information

B Cell Generation, Activation & Differentiation. B cell maturation

B Cell Generation, Activation & Differentiation. B cell maturation B Cell Generation, Activation & Differentiation Naïve B cells- have not encountered Ag. Have IgM and IgD on cell surface : have same binding VDJ regions but different constant region leaves bone marrow

More information

Fundamental Immunology (Introduction to the Immune System) By. Faculty of Medicine, Suez canal University, Ismailia EGYPT

Fundamental Immunology (Introduction to the Immune System) By. Faculty of Medicine, Suez canal University, Ismailia EGYPT Fogarty-IBRO School Nairobi-KENYA May 22 nd 25 th 2007 Fundamental Immunology (Introduction to the Immune System) By Ahmed El-Gohary, M.D. Faculty of Medicine, Suez canal University, Ismailia EGYPT The

More information

Natalia Taborda Vanegas. Doc. Sci. Student Immunovirology Group Universidad de Antioquia

Natalia Taborda Vanegas. Doc. Sci. Student Immunovirology Group Universidad de Antioquia Pathogenesis of Dengue Natalia Taborda Vanegas Doc. Sci. Student Immunovirology Group Universidad de Antioquia Infection process Epidermis keratinocytes Dermis Archives of Medical Research 36 (2005) 425

More information

REVIEWS. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans FOCUS ON IMMUNE TOLERANCE

REVIEWS. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans FOCUS ON IMMUNE TOLERANCE FOCUS ON IMMUNE TOLERANCE REVIEWS Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans Maria-Grazia Roncarolo* and Manuela Battaglia* Abstract Substantial progress

More information

Chapter 43: The Immune System

Chapter 43: The Immune System Name Period Our students consider this chapter to be a particularly challenging and important one. Expect to work your way slowly through the first three concepts. Take particular care with Concepts 43.2

More information

Amphibian Immunology. Vertebrate Immunology. Lymphoid Organs 3/4/14

Amphibian Immunology. Vertebrate Immunology. Lymphoid Organs 3/4/14 Amphibian Immunology Heather Williamson University of Tennessee Department of Microbiology March 4, 2014 Vertebrate Immunology Lymphoid Organs 1 3/4/14 Immunity First Line of Defense 2 Innate Immunity:

More information

Study Guide for Immunobiology BIO401. Fall 2009 Eddies Final Study Guide

Study Guide for Immunobiology BIO401. Fall 2009 Eddies Final Study Guide Study Guide for Immunobiology BIO401. Fall 2009 Eddies Final Study Guide What are the two branches of the immune system? Which is the first to respond? Which is more specific? Give examples of components

More information

11/20/2011. Outline. Immune System Function. Terminology. Two Types of Immune Defense. Innate Immunity = Non Specific

11/20/2011. Outline. Immune System Function. Terminology. Two Types of Immune Defense. Innate Immunity = Non Specific Chapter 43 Immune System Outline I. Nonspecific Defenses A. Barrier B. Protective proteins C. Phagocytes D. Natural killer cells E. Inflammatory reaction II. Specific Defenses A. B cells Antibody mediated

More information

AN INTRODUCTION TO IMMUNOLOGY. Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital

AN INTRODUCTION TO IMMUNOLOGY. Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital AN INTRODUCTION TO IMMUNOLOGY Paul Thomas Unit 1 Department of Immunology St. Jude Children s Research Hospital CATEGORIES OF PATHOGENS Viruses (~0.2 microns) Bacteria (1-2 microns) Parasites (Millimeters)

More information

Test 4 Immune System (Chapters 20 & 21)

Test 4 Immune System (Chapters 20 & 21) Test 4 Immune System (Chapters 20 & 21) Name: Date: 1) The is the largest lymphoid organ. 1) A. lymph node B. spleen C. thymus D. tonsil 2) Tonsils promote memory of pathogens by. 2) A. secreting antibodies

More information

Making the switch to a safer CAR-T cell therapy

Making the switch to a safer CAR-T cell therapy Making the switch to a safer CAR-T cell therapy HaemaLogiX 2015 Technical Journal Club May 24 th 2016 Christina Müller - chimeric antigen receptor = CAR - CAR T cells are generated by lentiviral transduction

More information

The Immune System: A Tutorial

The Immune System: A Tutorial The Immune System: A Tutorial Modeling and Simulation of Biological Systems 21-366B Shlomo Ta asan Images taken from http://rex.nci.nih.gov/behindthenews/uis/uisframe.htm http://copewithcytokines.de/ The

More information

The role of IBV proteins in protection: cellular immune responses. COST meeting WG2 + WG3 Budapest, Hungary, 2015

The role of IBV proteins in protection: cellular immune responses. COST meeting WG2 + WG3 Budapest, Hungary, 2015 The role of IBV proteins in protection: cellular immune responses COST meeting WG2 + WG3 Budapest, Hungary, 2015 1 Presentation include: Laboratory results Literature summary Role of T cells in response

More information

Immune Checkpoint Blockade in Acute Myeloid Leukemia. Kinsey McCormick Hematology Fellow s Conference January 10, 2014

Immune Checkpoint Blockade in Acute Myeloid Leukemia. Kinsey McCormick Hematology Fellow s Conference January 10, 2014 Immune Checkpoint Blockade in Acute Myeloid Leukemia Kinsey McCormick Hematology Fellow s Conference January 10, 2014 Overview Overview of immune checkpoints Immune checkpoints as mechanism of immune evasion

More information

Master Answers for the Autoimmune Disease Small group

Master Answers for the Autoimmune Disease Small group Master Answers for the Autoimmune Disease Small group Master Answer for Cases 1A and 1B There are multiple possible etiologies of autoimmune endocrinopathies, but regardless of the precise cause, there

More information

Types of Hypersensitivity. Type I: Allergic Reactions. more on Allergic Reactions

Types of Hypersensitivity. Type I: Allergic Reactions. more on Allergic Reactions Chapter 19: Disorders of the Immune System 1. Hypersensitivity 2. Autoimmunity 3. Transplant Rejection 1. Hypersensitivity What is Hypersensitivity? Hypersensitivity is an immunological state in which

More information

Introduction. Question: IL 22 producing ILCs or T cells have a role in commensal bacteria containment

Introduction. Question: IL 22 producing ILCs or T cells have a role in commensal bacteria containment Introduction Commensal bacteria compartmentalization live commensal bacteria are anatomically restricted to the mucosal immune compartment Many layers of defense participate in this compartmentalization

More information

Presenter Disclosure: Renier J. Brentjens, MD, PhD. Nothing to disclose

Presenter Disclosure: Renier J. Brentjens, MD, PhD. Nothing to disclose Presenter Disclosure: Renier J. Brentjens, MD, PhD Nothing to disclose Adoptive Therapy of Cancer with T cells Genetically Targeted to Tumor Associated Antigens through the Introduction of Chimeric Antigen

More information

Microbiology AN INTRODUCTION EIGHTH EDITION

Microbiology AN INTRODUCTION EIGHTH EDITION TORTORA FUNKE CASE Microbiology AN INTRODUCTION EIGHTH EDITION Differentiate between innate and acquired immunity. Chapter 17 Specific Defenses of the Host: The Immune Response B.E Pruitt & Jane J. Stein

More information

The Adaptive Immune Response. B-cells

The Adaptive Immune Response. B-cells The Adaptive Immune Response B-cells FUNCTIONS OF THE IMMUNE SYSTEM: Recognize, destroy and clear a diversity of pathogens. Initiate tissue and wound healing processes. Recognize and clear damaged self

More information

LESSON 3: ANTIBODIES/BCR/B-CELL RESPONSES

LESSON 3: ANTIBODIES/BCR/B-CELL RESPONSES Introduction to immunology. LESSON 3: ANTIBODIES/BCR/B-CELL RESPONSES Today we will get to know: The antibodies How antibodies are produced, their classes and their maturation processes Antigen recognition

More information

Inflammation and Cancer

Inflammation and Cancer Inflammation and Cancer A H PD C C B P Why Care About The Role Inflammation In Cancer? In a state of perpetual activation, immune mediators (cytokines, chemokines, free radicals) may cause tissue damage

More information

Name (print) Name (signature) Period. (Total 30 points)

Name (print) Name (signature) Period. (Total 30 points) AP Biology Worksheet Chapter 43 The Immune System Lambdin April 4, 2011 Due Date: Thurs. April 7, 2011 You may use the following: Text Notes Power point Internet One other person in class "On my honor,

More information

A link between gut microbiota, mucosal immunity and autoimmune arthritis. Hsin-Jung Joyce Wu "Microbiota and man: the story about us

A link between gut microbiota, mucosal immunity and autoimmune arthritis. Hsin-Jung Joyce Wu Microbiota and man: the story about us A link between gut microbiota, mucosal immunity and autoimmune arthritis Microbes and Man The majority of microbes we encounter are gut microbiota that live mostly in harmony with their host Duodenum 10

More information

Functional comparison of cord and adult blood-derived dendritic cells. Title. Author(s) Wong, On-hang.; 黃安恆. Citation.

Functional comparison of cord and adult blood-derived dendritic cells. Title. Author(s) Wong, On-hang.; 黃安恆. Citation. Title Functional comparison of cord and adult blood-derived dendritic cells Advisor(s) Chiang, AKS; Huang, F Author(s) Wong, On-hang.; 黃安恆. Citation Issued Date 2004 URL http://hdl.handle.net/10722/31762

More information

SUMMARY AND CONCLUSIONS

SUMMARY AND CONCLUSIONS SUMMARY AND CONCLUSIONS Summary and Conclusions This study has attempted to document the following effects of targeting protein antigens to the macrophage scavenger receptors by maleylation. 1. Modification

More information

HUMORAL IMMUNE RE- SPONSES: ACTIVATION OF B CELLS AND ANTIBODIES JASON CYSTER SECTION 13

HUMORAL IMMUNE RE- SPONSES: ACTIVATION OF B CELLS AND ANTIBODIES JASON CYSTER SECTION 13 SECTION 13 HUMORAL IMMUNE RE- SPONSES: ACTIVATION OF B CELLS AND ANTIBODIES CONTACT INFORMATION Jason Cyster, PhD (Email) READING Basic Immunology: Functions and Disorders of the Immune System. Abbas,

More information

SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY

SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY SOPHOMORE DENTAL/OPTOMETRY MICROBIOLOGY SECTION: IMMUNOLOGY LYMPHOCYTE ACTIVATION Lecturer: Louis B. Justement, Ph.D. 934-1429 lbjust@uab.edu Objectives: To review the structure of the T and B cell antigen

More information

4.1 Autoimmune Diseases in GM-CSF- and GM-CSF/IL-3-Deficient Mice

4.1 Autoimmune Diseases in GM-CSF- and GM-CSF/IL-3-Deficient Mice 4. DISCUSSION 4.1 Autoimmune Diseases in GM-CSF- and GM-CSF/IL-3-Deficient Mice My studies indicate that GM-CSF and GM-CSF/IL-3 deficiency in mice on the C57Bl/6, but not on the Balb/c background, greatly

More information

Regulatory T cells, tumour immunity and immunotherapy

Regulatory T cells, tumour immunity and immunotherapy Regulatory T, tumour immunity and immunotherapy Weiping Zou Abstract Tumours express a range of antigens, including self-antigens. Regulatory T are crucial for maintaining T-cell tolerance to self-antigens.

More information

2) Macrophages function to engulf and present antigen to other immune cells.

2) Macrophages function to engulf and present antigen to other immune cells. Immunology The immune system has specificity and memory. It specifically recognizes different antigens and has memory for these same antigens the next time they are encountered. The Cellular Components

More information

Discussion of natural killer cells and innate immunity. Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213

Discussion of natural killer cells and innate immunity. Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213 Discussion of natural killer cells and innate immunity Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213 Myths in tumor immunology Cancer cells are ignored by the

More information

Latest advances in the treatment of mesothelioma

Latest advances in the treatment of mesothelioma Latest advances in the treatment of mesothelioma Assoc Prof Thomas John Medical Oncologist, NHMRC Fellow Olivia Newton-John Cancer Research Institute 28 th March 2015 Disclosures Nil relevant Honoraria:

More information

Rheumatoid arthritis: an overview. Christine Pham MD

Rheumatoid arthritis: an overview. Christine Pham MD Rheumatoid arthritis: an overview Christine Pham MD RA prevalence Chronic inflammatory disease affecting approximately 0.5 1% of the general population Prevalence is higher in North America (approaching

More information

TEMA 10. REACCIONES INMUNITARIAS MEDIADAS POR CÉLULAS.

TEMA 10. REACCIONES INMUNITARIAS MEDIADAS POR CÉLULAS. TEMA 10. REACCIONES INMUNITARIAS MEDIADAS POR CÉLULAS. The nomenclature of cytokines partly reflects their first-described function and also the order of their discovery. There is no single unified nomenclature,

More information

SYNERGISTIC ROLE OF IL-15 IN THE EPITHELIUM AND THE LAMINA PROPRIA IN CELIAC DISEASE PATHOGENESIS

SYNERGISTIC ROLE OF IL-15 IN THE EPITHELIUM AND THE LAMINA PROPRIA IN CELIAC DISEASE PATHOGENESIS SYNERGISTIC ROLE OF IL-15 IN THE EPITHELIUM AND THE LAMINA PROPRIA IN CELIAC DISEASE PATHOGENESIS Bana Jabri Department of Medicine Celiac Disease Center University of Chicago Ingested gluten Environmental

More information

Chapter 43: The Immune System

Chapter 43: The Immune System Name Period Our students consider this chapter to be a particularly challenging and important one. Expect to work your way slowly through the first three concepts. Take particular care with Concepts 43.2

More information

Induction of Immunological tolerance via T regulatory cells

Induction of Immunological tolerance via T regulatory cells Induction of Immunological tolerance via T regulatory cells A clinical reality or just a nice experiment in mice? Manuela Battaglia Induction of Immunological tolerance via T regulatory cells A clinical

More information

Activation and effector functions of HMI

Activation and effector functions of HMI Activation and effector functions of HMI Hathairat Thananchai, DPhil Department of Microbiology Faculty of Medicine Chiang Mai University 25 August 2015 ว ตถ ประสงค หล งจากช วโมงบรรยายน แล วน กศ กษาสามารถ

More information

Innate immunity: Definition and Importance. Updated: July 2015

Innate immunity: Definition and Importance. Updated: July 2015 Innate immunity: Definition and Importance Updated: July 2015 1 Contents INNATE IMMUNITY... 3 DEFINITION AND IMPORTANCE... 3 Overview of innate immunity in animals... 3 The innate immune system acts early

More information

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai Systems Biology: A Personal View XV. Network Medicine Sitabhra Sinha IMSc Chennai Diseases, Genes and Networks http://learn.genetics.utah.edu/ Now that we have the ability to sequence entire genomes, can

More information

Cytotoxic T Lymphocytes (CTLs) and NK Cells. Effector T cells. After activation, naïve T cells differentiate into effector and memory T cells

Cytotoxic T Lymphocytes (CTLs) and NK Cells. Effector T cells. After activation, naïve T cells differentiate into effector and memory T cells After activation, naïve T cells differentiate into effector and memory T cells Cytotoxic T Lymphocytes (CTLs) and NK Cells After activation, T cells remain in lymph nodes for 5-6 days Effector T cells

More information

Back to Index. 1. Immunological Tolerance and Autoimmunity 1. Tolerance. 2. Mechanisms of tolerance to self-antigens

Back to Index. 1. Immunological Tolerance and Autoimmunity 1. Tolerance. 2. Mechanisms of tolerance to self-antigens Back to Index 1. Immunological Tolerance and Autoimmunity 1. Tolerance Normally we do not make immune responses against our own tissue, a concept known as "self-tolerance". Determining how the immune system

More information

Overview. Transcriptional cascades. Amazing aspects of lineage plasticity. Conventional (B2) B cell development

Overview. Transcriptional cascades. Amazing aspects of lineage plasticity. Conventional (B2) B cell development Overview B cell development Transcriptional cascades Amazing aspects of lineage plasticity Conventional (B2) B cell development What happens to an autoreactive B cell? B1 vs B2 cells Key anatomical sites

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: adoptive_immunotherapy 11/1993 3/2016 3/2017 3/2016 Description of Procedure or Service The spontaneous regression

More information

AP BIOLOGY 2007 SCORING GUIDELINES (Form B)

AP BIOLOGY 2007 SCORING GUIDELINES (Form B) AP BIOLOGY 2007 SCORING GUIDELINES (Form B) Question 2 The defenses of the human body to the entry and establishment of a pathogen (disease-causing organism) can be divided into nonspecific responses and

More information

Genetics of autoimmune diseases disorders of immune homeostasis

Genetics of autoimmune diseases disorders of immune homeostasis Genetics of autoimmune diseases disorders of immune homeostasis Peter K. Gregersen* and Timothy W. Behrens Abstract In the past few years, our extensive knowledge of the mammalian immune system and our

More information

What are cytokines and chemokines? What do cytokines, chemokines and growth factors do? Lecture 11

What are cytokines and chemokines? What do cytokines, chemokines and growth factors do? Lecture 11 Lecture 11 T-cell Effector Mechanisms-II: Cytokine Secretion & T-cell Polarization September 21, 2005 Chris Schindler cws4@columbia.edu What do cytokines, chemokines and growth factors do? They direct

More information

Multiple choice questions: ANSWERS

Multiple choice questions: ANSWERS Multiple choice questions: ANSWERS Chapter 2. Modification of the gut microbiota to promote human health 1. Bacteriocins are: b. Bacterially produced heat-stable antimicrobial peptides 2. Prebiotics, probiotics,

More information

An Update On Autoimmune Diseases

An Update On Autoimmune Diseases California Association for Medical Laboratory Technology Distance Learning Program An Update On Autoimmune Diseases by Paula J. D Amore, Ph.D., D(AMBLI) Assistant Professor, Division of Health Sciences

More information

Immune tolerance. Lu,Linrong Institute of Immunology, ZJU

Immune tolerance. Lu,Linrong Institute of Immunology, ZJU 免疫耐受 Immune tolerance Lu,Linrong Institute of Immunology, ZJU Lu.Linrong@gmail.com g http://mypage.zju.edu.cn/llr Immunological Tolerance *Definition *History (Early l observations ) *Mechanism Central

More information

2006 7.012 Problem Set 6 KEY

2006 7.012 Problem Set 6 KEY 2006 7.012 Problem Set 6 KEY ** Due before 5 PM on WEDNESDAY, November 22, 2006. ** Turn answers in to the box outside of 68-120. PLEASE WRITE YOUR ANSWERS ON THIS PRINTOUT. 1. You create an artificial

More information

Figure 14.2 Overview of Innate and Adaptive Immunity

Figure 14.2 Overview of Innate and Adaptive Immunity I M M U N I T Y Innate (inborn) Immunity does not distinguish one pathogen from another Figure 14.2 Overview of Innate and Adaptive Immunity Our first line of defense includes physical and chemical barriers

More information

AUTOIMMUNITY AND AUTOIMMUNE DISEASES

AUTOIMMUNITY AND AUTOIMMUNE DISEASES 64 AUTOIMMUNITY AND AUTOIMMUNE DISEASES 64.1 INTRODUCTION Normally the function of immune system in our body is to recognize foreign elements and to destroy these before they could harm us either by humoral

More information

Characterisation of regulatory T cells during acute Friend retrovirus infection of mice.

Characterisation of regulatory T cells during acute Friend retrovirus infection of mice. Characterisation of regulatory T cells during acute Friend retrovirus infection of mice. Inaugural Dissertation for the Doctoral Degree of Dr. rer. nat. from the Faculty of Biology University of Duisburg-Essen,

More information

Frequency Of Autoreactive T Cells 3/5/2014. Circulation Of Activated Cells To The CNS

Frequency Of Autoreactive T Cells 3/5/2014. Circulation Of Activated Cells To The CNS Immune Basis of New MS Therapies Samia J Khoury, MD Director of Abou-Haidar Neuroscience Institute Director of Multiple Sclerosis Center Professor of Neurology AUBMC MS Center & Harvard Medical School

More information

Immune System. Chapter 24

Immune System. Chapter 24 Immune System Chapter 24 Chapter Outline Immunology Lymphatic System Non-specific defense a. Defense at body surface b. Inflammation c. Phagocytosis macrophages, neutrophils d. Opsonins Ig and C 3 b e.

More information

Chapter 39 - The Body Defenses

Chapter 39 - The Body Defenses Chapter 39 - The Body Defenses Immunity - refers to the body s ability to resist or eliminate potentially harmful foreign material s or abnormal cells Mechanisms include: 1. Defense against invading pathogens

More information

How to construct transgenic mice

How to construct transgenic mice How to construct transgenic mice Sandra Beer-Hammer Autumn School 2010 Bad Schandau Methods additional genetic information transgenic mouse line gene inactivation gene-deficient knockout mouse line Jak2

More information

The Immune System. Albert Urwyler University Hospital Basel, Switzerland

The Immune System. Albert Urwyler University Hospital Basel, Switzerland The Immune System Albert Urwyler University Hospital Basel, Switzerland albert.urwyler@unibas.ch Outline Invaders and Physical Barriers Innate Immune System AdapAve Immune System AnAbodies B Cells Clonal

More information

DNA METHYLATION AND THE CONCEPT OF EPIGENETICS

DNA METHYLATION AND THE CONCEPT OF EPIGENETICS DNA METHYLATION AND THE CONCEPT OF EPIGENETICS The term Epigenetics describes heritable genetic modifications that are not attributable to changes in the primary DNA sequence. Epigenetic modifications

More information

Benefits in oncology. Mechanism of action

Benefits in oncology. Mechanism of action Mechanism of action The word cancer refers to a number of different diseases that share a common trait: the rapid, unrestrained growth and spread of cells that can invade and destroy surrounding tissues,

More information

3. Ag-dependent rearrangement of receptors and cytoskeleton at the T APC contact site

3. Ag-dependent rearrangement of receptors and cytoskeleton at the T APC contact site Seminars in Immunology 15 (2003) 295 300 Imaging immune cell interactions and functions: SMACs and the Immunological Synapse Abraham Kupfer a,b,, Hannah Kupfer a a Departments of Pediatrics and Immunology,

More information

The Humoral Immune system Structure and Diversity

The Humoral Immune system Structure and Diversity The Humoral Immune system Structure and Diversity Discussion: Introduction Our immune system protects our bodies from the harmful affects of a dizzying array of disease causing pathogens. Although our

More information

Pathogens and the immune system

Pathogens and the immune system Review of lecture 7 Pathogens and the immune system Veronica Leautaud, Ph.D. vl2@ rice.edu BRC 511 / 530-lab Lecture 8 BIOE 301-Bioengineering and World Health Science Science is the human activity of

More information

MICROBIOLOGY - IMMUNOLOGY MODULE Dr Ronnie Russell

MICROBIOLOGY - IMMUNOLOGY MODULE Dr Ronnie Russell The Specific/Adaptive Immune Response The Third Line of Defence Is called specific immunity The body s ability to recognize and defend itself against distinct invaders and their products Is a smart system

More information

Institute of Biochemistry I - Pathobiochemistry

Institute of Biochemistry I - Pathobiochemistry Institute of Biochemistry I - Pathobiochemistry Johann Wolfgang Goethe-University Our mission It is the intention to elucidate biochemical signatures with relevance to inflammation and hypoxia, thus contributing

More information

Pathogens and the immune system

Pathogens and the immune system Pathogens and the immune system Veronica Leautaud, Ph.D. vl2@ rice.edu BRC 511 / 530-lab Lecture 8 BIOE 301-Bioengineering and World Health Review of lecture 7 Science Science is the human activity of

More information

OKT3. ~ The first mouse monoclonal antibody. used in clinical practice in the field of transplantation ~

OKT3. ~ The first mouse monoclonal antibody. used in clinical practice in the field of transplantation ~ g944202 潘 怡 心 OKT3 ~ The first mouse monoclonal antibody used in clinical practice in the field of transplantation ~ As everybody knows, OKT3 is the first mouse monoclonal antibody produced for the treatment

More information

A disease and antibody biology approach to antibody drug discovery

A disease and antibody biology approach to antibody drug discovery A disease and antibody biology approach to antibody drug discovery Björn Frendéus, PhD VP, Preclinical research Presenter: Björn Frendéus Date: 2011-11-08 1 Antibodies have revolutionized Cancer Treatment!

More information

Antigens have specific regions where antibodies bind to them Antigens are usually molecules on the surface of viruses or foreign cells Antigenic

Antigens have specific regions where antibodies bind to them Antigens are usually molecules on the surface of viruses or foreign cells Antigenic Bio 100 Guide 22 Antigens have specific regions where antibodies bind to them Antigens are usually molecules on the surface of viruses or foreign cells Antigenic determinants are the specific regions on

More information

PATHOGENESIS OF AIDS

PATHOGENESIS OF AIDS Neal Nathanson, MD Emeritus Professor Department of Microbiology University of Pennsylvania School of Medicine 1 Definitions Structure of HIV HIV entry and cell tropism HIV-cell interactions Course of

More information

7.013 Problem Set

7.013 Problem Set 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 types that Participate

More information

NEW CLINICAL RESEARCH OPTIONS IN PANCREATIC CANCER IMMUNOTHERAPY. Alan Melcher Professor of Clinical Oncology and Biotherapy Leeds

NEW CLINICAL RESEARCH OPTIONS IN PANCREATIC CANCER IMMUNOTHERAPY. Alan Melcher Professor of Clinical Oncology and Biotherapy Leeds NEW CLINICAL RESEARCH OPTIONS IN PANCREATIC CANCER IMMUNOTHERAPY Alan Melcher Professor of Clinical Oncology and Biotherapy Leeds CANCER IMMUNOTHERAPY - Breakthrough of the Year in Science magazine 2013.

More information

From Mystery Case to

From Mystery Case to From Mystery Case to Management Conundrum CULLEN DUTMER, MD ELIE HADDAD, MD, PHD C L I NICAL I M M U NOLOGY S O C I E T Y S C H OOL I N P R I MA RY I M M U NODEFICI ENCY D I S EA S ES 2015 Mystery Case

More information

Your Guide to HLH. Hemophagocytic Lymphohistiocytosis

Your Guide to HLH. Hemophagocytic Lymphohistiocytosis Your Guide to HLH Hemophagocytic Lymphohistiocytosis What is HLH? Pronounced: HEE-moh-FA-goh-SIH-tik LIM-foh-HIS-tee-oh-sy-TOH-sis Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening

More information