Anti-Ly9 (CD229) antibody treatment reduces marginal zone B cell numbers and salivary gland inflammation in a mouse model of Sjögren s Syndrome
|
|
- Allan Price
- 5 years ago
- Views:
Transcription
1 Anti-Ly9 (CD229) antibody treatment reduces marginal zone B cell numbers and salivary gland inflammation in a mouse model of Sjögren s Syndrome Joan Puñet-Ortiz, Manuel Sáez Moya, Marta Cuenca, Adriana Lázaro, Pablo Engel Immunology Unit, Department of Biomedical Sciences, Medical School, University of Barcelona, C/ Casanova 143, 836 Barcelona, Spain. Barcelona, November 218
2 Ly9 (CD229) IS AN IMPORTANT IMMUNE-MODULATOR OF AUTOIMMUNIT AND B CELLS Ly9 (CD229) Unique SLAM family molecule with 4 Ig-like domains. V Ly9 interacts in a homophilic manner. C 2 V C 2 S S S S Expression restricted to lymphocytes. Highly expressed on innatelike lymphocytes, such as NKT cells and MZ B cells. Contains two immunoreceptor tyrosine-based switch motifs (ITSM) in its cytoplasmic tail. Recruits SAP adaptor molecule or phosphatases (SHP2 or SHIP-1) ITSM=Immunoreceptor tyrosine-basedswitchmotif Aged Ly9-deficient mice spontaneously develop features of systemic autoimmunity (de Salort et al., Front Immunol 213) Ly9 is a negative regulator for the development of marginal zone B cells (Cuenca et al., J Immunol 215)
3 SJÖGREN S SNDROME (SjS) MA BE A POTENTIAL TARGET FOR Ly9 TARGETING SjS is a common chronic autoimmune disease affecting salivary/lacrimal glans (dryness) but also extraglandular tissues Presence of autoantibodies (anti-dsdna, anti- Ro, Rheumatoid Factor) are key markers B-cell hyperactivity induces MZ B cell expansion that can lead to MZ-B cell lymphoma B cells play a key role in both humans and mice SjS All current therapies have failed Murine models are essential to understand its pathophysiology Salivary gland tissue with lymphocytic infiltrate. Voulgarelis, M. & Tzioufas, A. G. Nat. Rev. Rheumatol. 6, (21). Lymphocytic CD3 and CD2 cell infiltrate. x2
4 THE NOD.H-2 h4 MICE: AN SPONTANEOUS MODEL OF SJS-LIKE DISEASE The NOD.H-2 h4 mice spontaneously develope SjS-like disease but not diabetes At 24 weeks-old all female mice have SjS-related autoantibodies and salivary gland infiltrates The NOD.H-2 h4 mice show abnormal MZ B cell pool enlargment Spleen Balb/c MZ 3,37% NOD.H2 h4 MZ 24.6% Salivary Gland infiltrateof NODH2h4 mice. 1x. CD21 CD23
5 Previous results demonstrated that treatment of mice with, an agonistic mab against moue Ly9, had a dramatic effect on splenic MZ and B1 B cells. Since these two subsets of innate-like B cells have been postulated to be essential players in SjS in both humans and mice, we decided to test the hypothesis that injection with may be able to hinder the development of autoimmunity in NOD.H-2 h4 mice Specific Objectives 1. To test the ability of to deplete the MZ B cells and other subsets in the murine model of SjS NOD.H-2 h4. 2. To check if treatment with anti-ly9 mab have an impact on salivary gland infiltrates of d NOD.H-2 h4 mice. 3. To assess if treatment is able to reduce the levels of autoantibodies in NOD.H-2 h4 mice. 4. To prove if anti-ly9 mab is able to protect NOD.H-2 h4 mice from developing SjS disease. NOD.H-2 h4 Autoantibodies Salivary Gland infiltrate 8w 24w 27w 3w 25µg/mouse 25µg/mouse End-point evaluation Read-out: Organs - Spleen - Draining LN - Salivary Gland - Kidney Plasma
6 Results: MZ, B1 and GC B cells are depleted in different lymphoid organs CD21 CD95 Spleen % of lymphocytes CD23 Gated on B22 + MZ: 32.9% GL FO: 56.8% Gated on B22 + GC:.52% MZ: 1.45% **** **** ** B1 B1a B1b FO: 86.8% GC:.82% Control x1 6 lymphocytes MZ B cells (% of B22 + ) GC B cells (% of B22 + ) **** 8 Control MZ B cells (x1 6 ) ***.2 GC B cells (x1 6 ) Control ** **** **** ** B1 B1a B1b Draining LN CD21 CD95 CD23 Gated on B22 + MZ: 4.16% GL7 FO: 87.9% Gated on B22 + GC: 1.59% MZ: 1.29% FO: 93.2% GC:.15% MZ B cells (% of B22 + ) GC B cells (% of B22 + ) ***.2 MZ B cells (x1 6 ) Control Control GC B cells (x1 6 ) **
7 Results: Salivary gland area of infiltrate is reduced in anti-ly9 treated NOD.H-2 h4 mice Salivary Gland 1x 1x B22 + CD3 B22 + CD3 1x 1x B22 + CD3 4x B22 + CD3 4x B22 + CD4 B22 + CD4 1x 1x B22 + CD8 B22 + CD8
8 Results: Treatment with is able to affect autoantibodies levels Serum pre-treatment 1/32 4x 1/32 4x ANAs titers (dilution) 1, * anti-dsdna IgG (µg/ml) * post-treatment 1/32 4x 1/32 4x Rheumatoid Factor (IgM) (O.D.) ** anti-ro52 IgG (O.D.)
9 Results: Early treatment with is able to protect from salivary gland infiltration Salivary Gland Autoantibodies Salivary Gland infiltrate 8w 12w 14w 24w 27w 3w NOD.H-2 h4 25µg/mouse End-point evaluation A 1 B.5 Foci Number Total Area of Infiltrate (mm 2 ) Untreated Untreated 12-weeks-old 14-weeks-old 12-weeks-old 14-weeks-old
10 CONCLUSIONS Ly9 (CD229) targeting is able to deplete MZ, B1 and GC B cells in the spleen and draining lymph nodes Mice treated with the mab anti-ly9 show reduced area of lymphocyte infiltrates in the salivary glands The administration of is capable to affect autoantibody levels in mouse sera Early anti-ly9 mab treatment before disease onset impedes salivary gland infiltration In contrast with the B cell depletion therapies, the selective deletion of MZ, B1 and GC B cells should be regarded as an attractive new therapeutic approach
11 THANKS! Pablo Engel Manu Sáez Adriana Lázaro Marta Cuenca
Early Life Intervention Diminishes Manifestations. NOD.H-2 h4 mice. Tamer Mahmoud. Rachel Ettinger. Postdoctoral Fellow.
Early Life Intervention Diminishes Manifestations of Sjögren's Syndrome in NOD.H-2 h4 mice Tamer Mahmoud Postdoctoral Fellow Rachel Ettinger Senior Scientist Clinical Manifestations of Sjögren s Syndrome
More informationLPS CD40 + IL-4. Vorinostat (24 Hours) Vorinostat (24 Hours) Panobinostat (24 Hours) Panobinostat (24 Hours) Romidepsin (48 Hours)
A) CD + IL- B) LPS ( Hours) ( Hours) Cell number (x1-3 ) 1 1 3.7 M 1. M. M.1 M Cell number (x1 - ) 1 1 3. M 1. M.7 M.38 M Cell number (x1-3 ) Cell number (x1-3 ) 3 1 1 1 ( Hours) 7.nM.nM 1.7nM.nM Romidepsin
More informationSupporting Information Table of Contents
Supporting Information Table of Contents Supporting Information Figure 1 Page 2 Supporting Information Figure 2 Page 4 Supporting Information Figure 3 Page 5 Supporting Information Figure 4 Page 6 Supporting
More informationSUPPLEMENTARY INFORMATION
doi:1.138/nature1554 a TNF-α + in CD4 + cells [%] 1 GF SPF 6 b IL-1 + in CD4 + cells [%] 5 4 3 2 1 Supplementary Figure 1. Effect of microbiota on cytokine profiles of T cells in GALT. Frequencies of TNF-α
More informationSUPPLEMENTARY FIGURE 1
SUPPLEMENTARY FIGURE 1 A LN Cell count (1 ) 1 3 1 CD+ 1 1 CDL lo CD hi 1 CD+FoxP3+ 1 1 1 7 3 3 3 % of cells 9 7 7 % of cells CD+ 3 1 % of cells CDL lo CD hi 1 1 % of CD+ cells CD+FoxP3+ 3 1 % of CD+ T
More informationRegulatory B cells in autoimmunity. Liwei Lu University of Hong Kong, China
Regulatory B cells in autoimmunity Liwei Lu University of Hong Kong, China Multiple functions of B cells in immunity LeBien and Tedder, Blood (2008) B cell functions in autoimmune pathogenesis The Immunopathogensis
More informationSupporting Information
Supporting Information Desnues et al. 10.1073/pnas.1314121111 SI Materials and Methods Mice. Toll-like receptor (TLR)8 / and TLR9 / mice were generated as described previously (1, 2). TLR9 / mice were
More informationSupplemental Figure 1. Cell-bound Cetuximab reduces EGFR staining intensity. Blood
Antibody-mediated depletion of CD19-CAR T cells Supplemental 1 Supplemental Materials Supplemental Figure 1. Supplemental Figure 1. Cell-bound Cetuximab reduces EGFR staining intensity. Blood cells were
More informationNew Therapeutic Perspectives in Sjögren's Syndrome
New Therapeutic Perspectives in Sjögren's Syndrome Claudio Vitali Chairman of the EULAR Task Force for Disease Activity Criteria in Sjögren s Syndrome. Member of the Steering Committee for the ACR- EULAR
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 informationAntigen Presentation and T Lymphocyte Activation. Abul K. Abbas UCSF. FOCiS
1 Antigen Presentation and T Lymphocyte Activation Abul K. Abbas UCSF FOCiS 2 Lecture outline Dendritic cells and antigen presentation The role of the MHC T cell activation Costimulation, the B7:CD28 family
More informationEosinophils are required. for the maintenance of plasma cells in the bone marrow
Eosinophils are required for the maintenance of plasma cells in the bone marrow Van Trung Chu, Anja Fröhlich, Gudrun Steinhauser, Tobias Scheel, Toralf Roch, Simon Fillatreau, James J. Lee, Max Löhning
More informationImmunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells
Immunology Basics Relevant to Cancer Immunotherapy: T Cell Activation, Costimulation, and Effector T Cells Andrew H. Lichtman, M.D. Ph.D. Department of Pathology Brigham and Women s Hospital and Harvard
More informationGeneration of Robust Antibody Responses to HIV-1 MPER Antigens in Mice Reconstituted with Cultured B cells
Generation of Robust Antibody Responses to HIV-1 MPER Antigens in Mice Reconstituted with Cultured B cells T. Matt Holl 1, Masayuki Kuraoka 1, Dongmei Liao 1, Laurent Verkoczy 2, M. Anthony Moody 2, Munir
More informationNK cell flow cytometric assay In vivo DC viability and migration assay
NK cell flow cytometric assay 6 NK cells were purified, by negative selection with the NK Cell Isolation Kit (Miltenyi iotec), from spleen and lymph nodes of 6 RAG1KO mice, injected the day before with
More informationT Lymphocyte Activation and Costimulation. FOCiS. Lecture outline
1 T Lymphocyte Activation and Costimulation Abul K. Abbas, MD UCSF FOCiS 2 Lecture outline T cell activation Costimulation, the B7:CD28 family Inhibitory receptors of T cells Targeting costimulators for
More informationNormal GC initiation then collapse; normal mutation and 10. Constitutive signalling leads to spontaneous GC in PP, even BCR -/- 19
S1 Genetic modifications affecting germinal-centre formation and function Gene Compartment GC Phenotype Ref LTα, LTβ, TNF, Organ Disorganized lymphoid architecture in spleens; poor 1 TNFRI, LTβR architecture
More informationMolecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU
Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU Lecture outline Time 10:00 11:00 11:15 12:10 12:20 13:15 Content Introduction to lymphoma Review of lymphocyte biology
More informationSupplemental Table I.
Supplemental Table I Male / Mean ± SEM n Mean ± SEM n Body weight, g 29.2±0.4 17 29.7±0.5 17 Total cholesterol, mg/dl 534.0±30.8 17 561.6±26.1 17 HDL-cholesterol, mg/dl 9.6±0.8 17 10.1±0.7 17 Triglycerides,
More informationAcquired Immunity 2. - Vaccines & Immunological Memory - Wataru Ise. WPI Immunology Frontier Research Center (IFReC) Osaka University.
Acquired Immunity 2 - Vaccines & Immunological Memory - Wataru Ise WPI Immunology Frontier Research Center (IFReC) Osaka University Outline 1. What is vaccine (vaccination)? 2. What is immunological memory?
More informationAntigen Presentation and T Lymphocyte Activation. Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School. FOCiS
1 Antigen Presentation and T Lymphocyte Activation Shiv Pillai MD, PhD Massachusetts General Hospital Harvard Medical School FOCiS 2 Lecture outline Overview of T cell activation and the rules of adaptive
More informationSUPPLEMENTARY MATERIALS
SUPPLEMENTARY MATERIALS Supplementary Table 1. Demographic and clinical characteristics of the primary Sjögren's syndrome patient cohort Number % Females/males 73/5 93.6/6.4 Age, median (range) years 65
More informationSupplementary Information:
Supplementary Information: Follicular regulatory T cells with Bcl6 expression suppress germinal center reactions by Yeonseok Chung, Shinya Tanaka, Fuliang Chu, Roza Nurieva, Gustavo J. Martinez, Seema
More informationB cell activation and antibody production. Abul K. Abbas UCSF
1 B cell activation and antibody production Abul K. Abbas UCSF 2 Lecture outline B cell activation; the role of helper T cells in antibody production Therapeutic targeting of B cells 3 Principles of humoral
More informationImmune responses in autoimmune diseases
Immune responses in autoimmune diseases Erika Jensen-Jarolim Dept. of Pathophysiology Medical University Vienna CCHD Lecture January 24, 2007 Primary immune organs: Bone marrow Thymus Secondary: Lymph
More informationA. Incorrect! The duodenum drains to the superior mesenteric lymph nodes. B. Incorrect! The jejunum drains to the superior mesenteric lymph nodes.
USMLE Step 1 Problem Drill 11: Immunology Question No. 1 of 10 1. A 67 year old man is discovered to have metastatic disease involving his inferior mesenteric lymph nodes. His primary cancer is most likely
More informationImmunopathogenesis of SLE and Rationale for Biologic Therapy
Immunopathogenesis of SLE and Rationale for Biologic Therapy Peter Lipsky, MD Editor, Arthritis Research and Therapy Bethesda, MD Environmental Triggers, Gender, and Genetic Factors Contribute to SLE Pathogenesis
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nature10134 Supplementary Figure 1. Anti-inflammatory activity of sfc. a, Autoantibody immune complexes crosslink activating Fc receptors, promoting activation of macrophages, and WWW.NATURE.COM/NATURE
More informationRestoring Immune Function of Tumor-Specific CD4 + T Cells during Recurrence of Melanoma
Restoring Immune Function of Tumor-Specific CD4 + T Cells during Recurrence of Melanoma Goding SR et al. J Immunol 2013; 190:4899-4909 C. Nikolowsky Christian Doppler Laboratory for Cardiac and Thoracic
More informationErbb2 transgenic mice: a tool to evaluate the potential efficacy of vaccination in the prevention and cure of carcinomas
1 st International MUGEN Conference on Animal Models for Human Immunological Disease Athens, 11 September 2006 Erbb2 transgenic mice: a tool to evaluate the potential efficacy of vaccination in the prevention
More informationChapter 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 informationSupplementary Figure 1. Characterization of basophils after reconstitution of SCID mice
Supplementary figure legends Supplementary Figure 1. Characterization of after reconstitution of SCID mice with CD4 + CD62L + T cells. (A-C) SCID mice (n = 6 / group) were reconstituted with 2 x 1 6 CD4
More informationRegulation of Germinal Center Reactions by B and T Cells
Antibodies 2013, 2, 554-586; doi:10.3390/antib2040554 Review OPEN ACCESS antibodies ISSN 2073-4468 www.mdpi.com/journal/antibodies Regulation of Germinal Center Reactions by B and T Cells Young Uk Kim
More informationRole of BAFF in B cell Biology and Autoimmunity
Role of BAFF in B cell Biology and Autoimmunity B cell development in health and disease: B-lymphocytes or B cells, and the antibodies they produce, are crucial mediators of humoral immunity, providing
More informationAdaptive immune responses: T cell-mediated immunity
MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,
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 informationMODELLING THE HUMAN IMMUNE RESPONSE
MODELLING THE HUMAN IMMUNE RESPONSE Professor John Gordon MRC Centre for Immune Regulation Institute of Biomedical Research The Medical School Birmingham, UK Slides available for download at: www.celentyx.com
More informationSUPPORTING INFORMATIONS
SUPPORTING INFORMATIONS Mice MT/ret RetCD3ε KO α-cd25 treated MT/ret Age 1 month 3 mnths 6 months 1 month 3 months 6 months 1 month 3 months 6 months 2/87 Survival 87/87 incidence of 17/87 1 ary tumor
More information% of live splenocytes. STAT5 deletion. (open shapes) % ROSA + % floxed
Supp. Figure 1. a 14 1 1 8 6 spleen cells (x1 6 ) 16 % of live splenocytes 5 4 3 1 % of live splenocytes 8 6 4 b 1 1 c % of CD11c + splenocytes (closed shapes) 8 6 4 8 6 4 % ROSA + (open shapes) % floxed
More informationPrimary Immunodeficiency
Primary Immunodeficiency DiGeorge Syndrome Severe Combined Immunodeficiency SCID X-Linked Agammaglobulinemia Common variable immunodeficiency (CVID) IgA deficiency Hyper- IgM Syndrome Wiskott-Aldrich syndrome
More informationDetection of Anti-nuclear Antibodies in Women with Hyperprolactinaemia
Detection of Anti-nuclear Antibodies in Women with Hyperprolactinaemia Salahdeen Ismail Mohammed 12, Alaaeldeen Balal Ahmed 1, Nuha Abdurhaman 2, Abdalla Hassan Sharief 2 1 Faculty of Medical Laboratory
More informationT Cell Activation, Costimulation and Regulation
1 T Cell Activation, Costimulation and Regulation Abul K. Abbas, MD University of California San Francisco 2 Lecture outline T cell antigen recognition and activation Costimulation, the B7:CD28 family
More informationChapter 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 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 informationImmunology 2011 Lecture 17 Lymphoid Tissue Architecture 13 October
Immunology 2011 Lecture 17 Lymphoid Tissue Architecture 13 October TODAY Lymphoid Tissue Architecture, Chap. 16 APC Antigen processing (dendritic cells, MΦ et al.) Antigen "presentation" Ag/Ab complexes
More informationHow the Innate Immune System Profiles Pathogens
How the Innate Immune System Profiles Pathogens Receptors on macrophages, neutrophils, dendritic cells for bacteria and viruses Broad specificity - Two main groups of bacteria: gram positive, gram-negative
More informationAutoimmune diseases. SLIDE 3: Introduction to autoimmune diseases Chronic
SLIDE 3: Introduction to autoimmune diseases Chronic Autoimmune diseases Sometimes relapsing : and remitting. which means that they present as attacks Progressive damage Epitope spreading more and more
More informationT Cell Activation. Patricia Fitzgerald-Bocarsly March 18, 2009
T Cell Activation Patricia Fitzgerald-Bocarsly March 18, 2009 Phases of Adaptive Immune Responses Phases of T cell responses IL-2 acts as an autocrine growth factor Fig. 11-11 Clonal Expansion of T cells
More informationInnate immunity (rapid response) Dendritic cell. Macrophage. Natural killer cell. Complement protein. Neutrophil
1 The immune system The immune response The immune system comprises two arms functioning cooperatively to provide a comprehensive protective response: the innate and the adaptive immune system. The innate
More informationLoss of early innate immune control leads to severe EBV
Loss of early innate immune control leads to severe EBV Disease The History of Epstein Barr Virus Glandular Fever (Drusenfieber), Pfeiffer, 1889 Infectious Mononucleosis, Sprunt, 1920 The History of Epstein
More informationWhat will we discuss today?
Autoimmune diseases What will we discuss today? Introduction to autoimmune diseases Some examples Introduction to autoimmune diseases Chronic Sometimes relapsing Progressive damage Epitope spreading more
More informationHematology 101. Rachid Baz, M.D. 5/16/2014
Hematology 101 Rachid Baz, M.D. 5/16/2014 Florida 101 Epidemiology Estimated prevalence 8,000 individuals in U.S (compare with 80,000 MM patients) Annual age adjusted incidence 3-8/million-year 1 More
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 informationSupplementary Figure 1: Expression of NFAT proteins in Nfat2-deleted B cells (a+b) Protein expression of NFAT2 (a) and NFAT1 (b) in isolated splenic
Supplementary Figure 1: Expression of NFAT proteins in Nfat2-deleted B cells (a+b) Protein expression of NFAT2 (a) and NFAT1 (b) in isolated splenic B cells from WT Nfat2 +/+, TCL1 Nfat2 +/+ and TCL1 Nfat2
More informationSupporting Information
Supporting Information lpek et al. 1.173/pnas.1121217 SI Materials and Methods Mice. cell knockout, inos / (Taconic arms), Rag1 /, INγR /, and IL-12p4 / mice (The Jackson Laboratory) were maintained and/or
More informationSpleen. mlns. E Spleen 4.1. mlns. Spleen. mlns. Mock 17. Mock CD8 HIV-1 CD38 HLA-DR. Ki67. Spleen. Spleen. mlns. Cheng et al. Fig.
C D E F Mock 17 Mock 4.1 CD38 57 CD8 23.7 HLA-DR Ki67 G H I Cheng et al. Fig.S1 Supplementary Figure 1. persistent infection leads to human T cell depletion and hyper-immune activation. Humanized mice
More informationPathology of the indolent B-cell lymphomas Elias Campo
Pathology of the indolent B-cell lymphomas Elias Campo Hospital Clinic, University of Barcelona Small B-cell lymphomas Antigen selection NAIVE -B LYMPHOCYTE MEMORY B-CELL MCL FL LPL MZL CLL Small cell
More informationInnate immunity. Abul K. Abbas University of California San Francisco. FOCiS
1 Innate immunity Abul K. Abbas University of California San Francisco FOCiS 2 Lecture outline Components of innate immunity Recognition of microbes and dead cells Toll Like Receptors NOD Like Receptors/Inflammasome
More informationLymphatic System. Where s your immunity idol?
Lymphatic System Where s your immunity idol? Functions of the Lymphatic System Fluid Balance Drains excess fluid from tissues Lymph contains solutes from plasma Fat Absorption Lymphatic system absorbs
More informationImmunity and Cancer. Doriana Fruci. Lab di Immuno-Oncologia
Immunity and Cancer Doriana Fruci Lab di Immuno-Oncologia Immune System is a network of cells, tissues and organs that work together to defend the body against attacks of foreign invaders (pathogens, cancer
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 informationChapter 24 The Immune System
Chapter 24 The Immune System The Immune System Layered defense system The skin and chemical barriers The innate and adaptive immune systems Immunity The body s ability to recognize and destroy specific
More informationCHAPTER 9 BIOLOGY OF THE T LYMPHOCYTE
CHAPTER 9 BIOLOGY OF THE T LYMPHOCYTE Coico, R., Sunshine, G., (2009) Immunology : a short course, 6 th Ed., Wiley-Blackwell 1 CHAPTER 9 : Biology of The T Lymphocytes 1. 2. 3. 4. 5. 6. 7. Introduction
More informationFOCiS. Lecture outline. The immunological equilibrium: balancing lymphocyte activation and control. Immunological tolerance and immune regulation -- 1
1 Immunological tolerance and immune regulation -- 1 Abul K. Abbas UCSF FOCiS 2 Lecture outline Principles of immune regulation Self-tolerance; mechanisms of central and peripheral tolerance Inhibitory
More informationT cell and Cell-mediated immunity
T cell and Cell-mediated immunity ( 第十章 第十二章第十二章 ) Lu Linrong ( 鲁林荣 ) PhD Laboratory of Immune Regulation Institute of Immunology Zhejiang University, School of Medicine Medical Research Building B815-819
More informationDC were seeded into tissue culture dishes in IMDM 2% FCS, and added with PMN. (1:1; PMN: DC) for 16h also in the presence of DNAse (100 U/ml); DC were
Supplementary methods Flow cytometric analysis of DCs. DC were seeded into tissue culture dishes in IMDM 2% FCS, and added with PMN (1:1; PMN: DC) for 16h also in the presence of DNAse (100 U/ml); DC were
More informationImmunobiology 7. The Humoral Immune Response
Janeway Murphy Travers Walport Immunobiology 7 Chapter 9 The Humoral Immune Response Copyright Garland Science 2008 Tim Worbs Institute of Immunology Hannover Medical School 1 The course of a typical antibody
More informationAssociation of anti-mcv autoantibodies with SLE (Systemic Lupus Erythematosus) overlapping with various syndromes
International Journal of Medicine and Medical Sciences Vol. () pp. 21-214, June 211 Available online http://www.academicjournals.org/ijmms ISSN 2-972 211 Academic Journals Full Length Research Paper Association
More informationUnit 5 The Human Immune Response to Infection
Unit 5 The Human Immune Response to Infection Unit 5-page 1 FOM Chapter 21 Resistance and the Immune System: Innate Immunity Preview: In Chapter 21, we will learn about the branch of the immune system
More informationand follicular helper T cells is Egr2-dependent. (a) Diagrammatic representation of the
Supplementary Figure 1. LAG3 + Treg-mediated regulation of germinal center B cells and follicular helper T cells is Egr2-dependent. (a) Diagrammatic representation of the experimental protocol for the
More informationAUTOIMMUNITY CLINICAL CORRELATES
AUTOIMMUNITY CLINICAL CORRELATES Pamela E. Prete, MD, FACP, FACR Section Chief, Rheumatology VA Healthcare System, Long Beach, CA Professor of Medicine, Emeritus University of California, Irvine Colonel
More informationSupplementary Figure 1 Protease allergens induce IgE and IgG1 production. (a-c)
1 Supplementary Figure 1 Protease allergens induce IgE and IgG1 production. (a-c) Serum IgG1 (a), IgM (b) and IgG2 (c) concentrations in response to papain immediately before primary immunization (day
More informationAUTOIMMUNITY TOLERANCE TO SELF
AUTOIMMUNITY CLINICAL CORRELATES Pamela E. Prete, MD, FACP, FACR Section Chief, Rheumatology VA Healthcare System, Long Beach, CA Professor of Medicine, Emeritus University of California, Irvine Colonel
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 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 informationAutoimmunity and Primary Immune Deficiency
Autoimmunity and Primary Immune Deficiency Mark Ballow, MD Division of Allergy & Immunology USF Morsani School of Medicine Johns Hopkins All Children s Hospital St Petersburg, FL The Immune System What
More informationT Cell Effector Mechanisms I: B cell Help & DTH
T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide
More informationSupplementary Figure 1. Generation of knockin mice expressing L-selectinN138G. (a) Schematics of the Sellg allele (top), the targeting vector, the
Supplementary Figure 1. Generation of knockin mice expressing L-selectinN138G. (a) Schematics of the Sellg allele (top), the targeting vector, the targeted allele in ES cells, and the mutant allele in
More informationEffector 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 information3. Lymphocyte proliferation (fig. 15.4): Clones of responder cells and memory cells are derived from B cells and T cells.
Chapter 15 Adaptive, Specific Immunity and Immunization* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. Specific
More informationAdaptive immunity. Adaptive Immunity. Principles of immune defense. Adaptive immunity. against extracellular or intracellular pathogens
Principles of immune defense Toxicology Course Vienna MODULE 12 Immunotoxicology, Allergy July 2, 2008 Prof. Erika Jensen-Jarolim, MD Dept. of Pathophysiology Medical University Vienna Gastrointestinaltrakt:
More informationDendritic cells in cancer immunotherapy Aimin Jiang
Dendritic cells in cancer immunotherapy Aimin Jiang Feb. 11, 2014 Dendritic cells at the interface of innate and adaptive immune responses Dendritic cells: initiators of adaptive immune responses Dendritic
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 informationRequirements in the Development of an Autoimmune Disease Amino Acids in the Shared Epitope
+ T cell MHC/self-peptide MHC/Vβ Induction of + T H 1 mediated autoimmunity: A paradigm for the pathogenesis of rheumatoid arthritis, multiple sclerosis and type I diabetes APC Activated autoreactive +
More informationImmune receptors Y Y. Multiple immune responses CLR TLR NLR ITAM RLR. C-type lectin. ITAM: Immunoreceptor Tyrosine-based Activation Motif
C Immune receptors Innate immunity Acquired immunity TLR CLR FcR BCR TCR C-type lectin Y Y Ig Ig NLR ITAM ITAM ITAM RLR Multiple immune responses ITAM: Immunoreceptor Tyrosine-based Activation Motif Immune
More informationDisruption of Healthy Tissue by the Immune Response Autoimmune diseases: Inappropriate immune response against self-components
Chapter 13 Disruption of Healthy Tissue by the Immune Response Autoimmune diseases: Inappropriate immune response against self-components Humoral imm 胞外 胞內 CMI: CD8 T Self Ag Self(Auto) antigen (encoded
More informationPrepared by: Dr.Mansour Al-Yazji
C L L CLL Prepared by: Abd El-Hakeem Abd El-Rahman Abu Naser Ahmed Khamis Abu Warda Ahmed Mohammed Abu Ghaben Bassel Ziad Abu Warda Nedal Mostafa El-Nahhal Dr.Mansour Al-Yazji LEUKEMIA Leukemia is a form
More informationNKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies
NKTR-255: Accessing The Immunotherapeutic Potential Of IL-15 for NK Cell Therapies Saul Kivimäe Senior Scientist, Research Biology Nektar Therapeutics NK Cell-Based Cancer Immunotherapy, September 26-27,
More informationFollicular Lymphoma. ced3 APOPTOSIS. *In the nematode Caenorhabditis elegans 131 of the organism's 1031 cells die during development.
Harvard-MIT Division of Health Sciences and Technology HST.176: Cellular and Molecular Immunology Course Director: Dr. Shiv Pillai Follicular Lymphoma 1. Characterized by t(14:18) translocation 2. Ig heavy
More information3rd Pannonia Congress of Pathology. Slide seminar / Gastrointestinal pathology: Case Nr. 1. Lukáš Plank
3rd Pannonia Congress of Pathology Bled, May 16, 2014 Slide seminar / Gastrointestinal pathology: Case Nr. 1. Lukáš Plank National Consultation Center for Haematopathology in Slovakia: Department of Pathology,
More informationOut of the IgM B cells that develop daily in the
Published Online: 5 July, 1999 Supp Info: http://doi.org/10.1084/jem.190.1.75 Downloaded from jem.rupress.org on May 9, 2018 B Cell Development in the Spleen Takes Place in Discrete Steps and Is Determined
More informationHua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder I Nakaya, Kousik
SUPPLEMENTARY FIGURES 1-19 T H 2 response to cysteine-proteases requires dendritic cell-basophil cooperation via ROS mediated signaling Hua Tang, Weiping Cao, Sudhir Pai Kasturi, Rajesh Ravindran, Helder
More informationT-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 informationT-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 informationMACROPHAGE "MONOCYTES" SURFACE RECEPTORS
LECTURE: 13 Title: MACROPHAGE "MONOCYTES" SURFACE RECEPTORS LEARNING OBJECTIVES: The student should be able to: Describe the blood monocytes (size, and shape of nucleus). Enumerate some of the monocytes
More informationIMMUNOLOGICAL MEMORY. CD4 T Follicular Helper Cells. Memory CD8 T Cell Differentiation
IMMUNOLOGICAL MEMORY CD4 T Follicular Helper Cells Memory CD8 T Cell Differentiation CD4 T Cell Differentiation Bcl-6 T-bet GATA-3 ROR t Foxp3 CD4 T follicular helper (Tfh) cells FUNCTION Provide essential
More informationBlood and Immune system Acquired Immunity
Blood and Immune system Acquired Immunity Immunity Acquired (Adaptive) Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated
More informationSupplementary Figure S1. PTPN2 levels are not altered in proliferating CD8+ T cells. Lymph node (LN) CD8+ T cells from C57BL/6 mice were stained with
Supplementary Figure S1. PTPN2 levels are not altered in proliferating CD8+ T cells. Lymph node (LN) CD8+ T cells from C57BL/6 mice were stained with CFSE and stimulated with plate-bound α-cd3ε (10µg/ml)
More informationSpecific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice
Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice Marianne A. Bryan, Siobhan E. Guyach, Karen A. Norris* Department of Immunology,
More informationSUPPLEMENTAL INFORMATION. Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus
1 SUPPLEMENTAL INFORMATION 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17 18 19 2 21 22 23 24 25 26 27 28 29 3 31 32 33 34 35 36 37 38 39 4 Impaired TLR9 responses in B cells from patients with systemic lupus
More information