DOCSLIB.ORG

Transcriptome Reprogramming and Myeloid Skewing in Haematopoietic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transcriptome Reprogramming and Myeloid Skewing in Haematopoietic Ann Rheum Dis: first published as 10.1136/annrheumdis-2019-215782 on 28 November 2019. Downloaded from Systemic lupus erythematosus TRANSLATIONAL SCIENCE Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus Maria Grigoriou,1,2 Aggelos Banos,2 Anastasia Filia,2 Pavlos Pavlidis,3 Stavroula Giannouli,4 Vassiliki Karali,1 Dionysis Nikolopoulos,1,2 Antigone Pieta,1 George Bertsias,5 Panayotis Verginis,6 Ioannis Mitroulis,7,8 Dimitrios T Boumpas 1,2,9 Handling editor Josef S ABSTRact Key messages Smolen Objectives Haematopoietic stem and progenitor cells (HSPCs) are multipotent cells giving rise to both ► Additional material is What is already known about this subject? published online only. To view, myeloid and lymphoid cell lineages. We reasoned that ► Most cells participating in the pathogenesis of please visit the journal online the aberrancies of immune cells in systemic lupus systemic lupus erythematosus (SLE) originate (http:// dx. doi. org/ 10. 1136/ erythematosus (SLE) could be traced back to HSPCs. annrheumdis- 2019- 215782). from bone marrow (BM) haematopoietic stem Methods A global gene expression map of bone and progenitor cells (HSPCs). HSPCs actively For numbered affiliations see marrow (BM)-derived HSPCs was completed by RNA respond to inflammatory stimuli by myeloid end of article. sequencing followed by pathway and enrichment skewing, but this may lead to exhaustion, analysis. The cell cycle status and apoptosis status of decreased function, increased risk for Correspondence to HSPCs were assessed by flow cytometry, while DNA inflammation, decreased adaptive immunity Dr Dimitrios T Boumpas, 4th damage was assessed via immunofluorescence. Department of Internal − + + and increased cardiovascular mortality. Medicine, University Hospital, 1 Results Transcriptomic analysis of Lin Sca-1 c- Kit Riminis Street, 124 62 Chaidari, haematopoietic progenitors from diseased lupus mice What does this study add? Athens, Greece; demonstrated a strong myeloid signature with expanded boumpasd@ uoc. gr ► In SLE, there is evidence of deregulation frequencies of common myeloid progenitors (CMPs)— of haematopoiesis with skewing towards MG and AB contributed equally. but not of common lymphoid progenitors—reminiscent the myeloid lineage at the expense of of a ’trained immunity’ signature. CMP profiling lymphopoiesis and priming of HSPCs that Received 26 May 2019 revealed an intense transcriptome reprogramming exhibit a ‘trained immunity’ signature; this may Revised 30 September 2019 Accepted 18 October 2019 with suppression of granulocytic regulators indicative contribute to inflammation and risk of flare. of a differentiation arrest with downregulation trend of major regulators such as Cebpe, Cebpd and Csf3r, How might this impact on clinical practice or and disturbed myelopoiesis. Despite the differentiation future developments? arrest, frequencies of BM neutrophils were markedly ► Abnormalities of immune cells in SLE can increased in diseased mice, suggesting an alternative be traced back in the BM HSPCs, a disease http://ard.bmj.com/ granulopoiesis pathway. In patients with SLE with where stem cell therapy has been considered severe disease, haematopoietic progenitor cells for refractory cases. Re-establishment of the (CD34+) demonstrated enhanced proliferation, cell appropriate myeloid versus lymphoid balance differentiation and transcriptional activation of cytokines and alleviation of cell exhaustion may improve and chemokines that drive differentiation towards transplantability of HSPCs and may restore immune function. This could also decrease risk myelopoiesis, thus mirroring the murine data. on September 27, 2021 by guest. Protected copyright. Conclusions Aberrancies of immune cells in SLE can of infection and atherosclerosis and attenuate be traced back to the BM HSPCs. Priming of HSPCs and inflammation, decreasing the risk of flare. aberrant regulation of myelopoiesis may contribute to inflammation and risk of flare. Trial registration number 4948/19-07-2016. immune- complex depositions affects several organs, leading to significant morbidity.1 2 Haematopoietic stem and progenitor cells (HSPCs) represent the most primitive multipo- INTRODUCTION tent population giving rise to all blood cell types.3 © Author(s) (or their In systemic lupus erythematosus (SLE), an inter- HSPCs reside in the bone marrow (BM) niche employer(s)) 2019. Re- use play between environmental, genetic and epigenetic permitted under CC BY. and remain in a quiescent state. Under stress or Published by BMJ. factors leads to perturbation of complex biological inflammatory conditions, they respond by prolifer- networks culminating into diverse clinical pheno- ating and differentiating to replenish any progeny To cite: Grigoriou M, types. In this disease, interferon- alpha (IFN-α)- needed.4–6 Banos A, Filia A, et al. Ann Rheum Dis Epub ahead driven immunological alterations result in persistent A key observation in SLE is that most cells partic- of print: [please include Day immune responses against autologous nucleic acids, ipating in its pathogenesis, such as lymphocytes, Month Year]. doi:10.1136/ mimicking a sustained antiviral response. Intrac- monocytes and neutrophils, originate from HSPCs. annrheumdis-2019-215782 table tissue damage caused by autoantibodies or In a congenic strain of lupus mice, the function of Grigoriou M, et al. Ann Rheum Dis 2019;0:1–12. doi:10.1136/annrheumdis-2019-215782 1 Ann Rheum Dis: first published as 10.1136/annrheumdis-2019-215782 on 28 November 2019. Downloaded from Systemic lupus erythematosus hematopoietic stem cells is altered by both genetic and inflam- Mononuclear cell isolation and processing matory factors with evidence of increased self- renewal and resis- Bone marrow mononuclear cells (BMMCs) were isolated using tance to stress.7 In patients with SLE with cytopenias, BM exhibits Histopaque 1077 (Sigma- Aldrich). BMMCs were washed, and necrosis, stromal alterations, hypocellularity, dyspoiesis and erythrocytes were lysed with red blood cell buffer (420301, distortion of normal architecture with abnormal localisation of Biolegend) and stained with conjugated antibodies. CD34+ cells immature precursors aggregates.8 Gene expression studies from were isolated from BMMCs using magnetic beads (18056, Stem- our group have demonstrated upregulation of genes involved in Cell Technologies). cell death and granulopoiesis, providing further evidence of the 9 role of apoptosis and granulocytes in its pathogenesis. RNA sequencing Within the BM niche, inflammatory cytokines and myeloid- LSKs and CMPs were sorted from BM of NZBW/F1 and specific growth factors, including interleukin (IL)-1 and C57BL/6 mice. CD34+ cells were isolated from BMMCs. Genes 10 granulocyte macrophage growth factor, drive the repro- with a false discovery rate of ≤0.05 and a fold change of >1.5 gramming of HSPCs towards myeloid lineage by epigenetic were considered statistically significantly upregulated/downreg- modifications and induction of lineage- specific transcription ulated, respectively. For the human–mouse comparison, human factors. These alterations increase their adaptation to inflam- genes were converted to mouse orthologos and pathways were matory and haematopoietic stress, promoting the generation compared based on their ID. of myeloid cells that confer protection to secondary infection, in a phenomenon termed ‘trained innate immunity’ or ‘innate 11 12 Statistics immune memory’. Perturbed immunological imprinting Statistical analyses were performed using unpaired two-tailed (mediated by hyperactive and myeloid priming) could be Student’s t- test, while Mann- Whitney U test was used for the detrimental, exaggerating immune responses in autoimmune comparison of two groups. Data are presented as mean±SD. 13 14 15 and inflammatory diseases such as arthritis, SLE or Differences were considered statistically significant at p<0.05. 16–18 atherothrombosis. All data were analysed using GraphPad Prism V.5 software. We reasoned that the fundamental molecular aberrations in SLE (genetic or epigenetic) may be traced back in the HSPCs Study approval within the BM. To this end, we used the NZBW/F1 mouse Informed consent was obtained from all patients and HC prior to model of SLE to investigate the lupus transcriptome of HSPCs sample collection (Athens, Greece, protocol 10/22-6-2017). All and compared it with transcriptomic data from human SLE + procedures in mice were in accordance with institutional guide- CD34 cells. Herein, we report reprogramming of HSPCs lines and were reviewed and approved by the Greek Federal towards myeloid lineage—with evidence of a ‘trained immunity’ Veterinary Office (Athens, Greece). signature—and propose that this may contribute to exaggerated immune responses and flares in SLE. RESULTS The transcriptional profile of murine lupus HSPCs METHODS demonstrates myeloid skewing Mice To study whether HSPCs in SLE exhibit transcriptional alter- 21–23 C57BL/6 mice were purchased from the Jackson Laboratory. ations, we used the spontaneous mouse model NZBW/F1 NZB/OlaHsd and NZW/OlaHsd mice were purchased from at two time points: preclinical stage (F1- P) and clinical stage, Envigo. NZBW/F1 mice were considered diseased, when exhib- defined as the point with proteinuria of >100 ng/dL (F1- L). http://ard.bmj.com/ iting ≥100 ng/dL of urine protein after the completion of Age- matched female C57BL/6 mice served as controls (B6- Y and 6 months of their life.19 Age-
Load more

Recommended publications
  • Primer the Complement System
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE providedMagazine by ElsevierR259 - Publisher Connector vascular permeability and the infection. The second category Primer extravasation of plasma. This is in which there is persistent accompanied by the adhesion of formation of immune complexes is leukocytes to vascular endothelium autoimmune disease, in which, by The complement and their emigration into definition, the antigen is a system surrounding tissue. Complement permanent feature of the host. plays an important part in An understanding of how immune Philip Taylor, Marina inflammation, in helping to recruit complexes cause tissue injury effector cells and in promoting the developed from study of such Botto and Mark Walport killing and clearance of pathogens. diseases in humans and animals, and But complement can be both from the induction of experimental The system of plasma proteins called friend and foe. In some immune complex disease. In these complement was so-named because circumstances the activation of situations, immune complexes were it complements the activity of complement in response to immune shown to cause tissue injury through antibody in the lysis of bacteria. It complexes may cause harm: acutely activation of complement, as opsonin has a central role in host defence in the context of massive (binding to complement receptors on against many micro-organisms and in complement activation occurring in leukocytes) and as the source of the modulation of inflammatory patients with overwhelming Gram- anaphylatoxins (stimulating leukocyte reactions, an activity that has been negative bacterial sepsis, and chemotaxis and degranulation). But illuminated by the study of humans chronically, when an antibody the development of gene-targeted with naturally occurring deficiencies response develops in the context of mice with deficiencies of complement of complement.
    [Show full text]
  • Foundation Block Lecture Three Cell Mediated Immunity
    Foundation Block Lecture Five Hypersensitivity Objectives: • To know that hypersensitivity reactions are over and excessive immune responses that can be harmful to body in four different ways • To be familiar with inflammatory processes in type I hypersensitivity reaction that mediates allergic inflammation • To recognize that type II hypersensitivity deals with immune responses against antigens that are integral part of cell membrane and are usually associated with autoimmune disorders • To know that type III hypersensitivity reactions are mediated by immune complexes and cause vasculitis • To describe type IV hypersensitivity is a purely cell mediated immune response associated with chronic inflammation ● Important. ● Extra notes. ● Females notes ● Males notes. What is hypersensitivity? Protective immunity: desirable reaction. Hypersensitivity: undesirable damaging reaction produced by excessive immune reactions. - Undesirable responses can be mediated by: - Antibody binding to antigens (Types I-III). - Cell mediated reaction to chemicals or proteins (Type IV). Types of hypersensitivity: 4 Types of hypersensitivity responses are classified by GEL AND COOMBS (names of scientists) according to the responding mechanisms, NOT the responding antigens: *From 433 team Type I: 1- Also termed as: - Immediate Hypersensitivity. - Allergic reactions. (e.g. asthma and eczema) - Anaphylactic reactions: severe and rapidly progressing systemic forms which can be quickly life threatening. …..............(causes.vasodilation and hypovolemia which causes heart stop then death) 2- Most people will not react to these allergens but some individuals “atopic” respond by producing large amounts of IgE in …........response to those otherwise harmless substances. 3- Non-allergic individuals respond to these allergens by producing IgG antibodies. 4- Features: - Antibody type: IgE - Cellular components: Mast cells, basophiles & eosinophils - Antigens: Also known as allergens ( antigens with low molecular weight & highly soluble).
    [Show full text]
  • Suppression of Immune Complex-Induced Inflammation by the Chemotactic Factor Inactivator
    Suppression of immune complex-induced inflammation by the chemotactic factor inactivator. K J Johnson, … , T P Anderson, P A Ward J Clin Invest. 1977;59(5):951-958. https://doi.org/10.1172/JCI108717. Research Article Small amounts (10(-10) mol) of purified human chemotactic factor inactivator (CFI) suppress leukocytic infiltration, permeability changes, and hemorrhage associated with acute immune complex-induced injury in rats. The reversed passive dermal Arthus reaction and acute immune complex-induced alveolitis in rats have served as the model systems of inflammation. The mechanism of inhibition does not appear to relate to interference with formation and deposition of immune complexes, or with fixation of complement in vitro or iv vivo. Human CFI inhibits in vitro the chemotactic activity generated in complement-activated rat serum. The inhibitory effects of human CFI are not seen if it is first heat inactivated. The data provide the first direct support for the conclusion that CFI has anti-inflammatory activity. Find the latest version: https://jci.me/108717/pdf Suppression of Immune Complex-Induced Inflammation by the Chemotactic Factor Inactivator KENT J. JOHNSON, THOMAS P. ANDERSON, and PETER A. WARD From the Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06032 A B S T RA C T Small amounts (10-10 mol) of purified fested by skin tests (7-10). These observations have human chemotactic factor inactivator (CFI) suppress suggested that CFI is an important regulator of the leukocytic infiltration, permeability changes, and inflammatory response. In this communication direct hemorrhage associated with acute immune complex- evidence is presented to show that purified human CFI induced injury in rats.
    [Show full text]
  • Understanding the Immune System: How It Works
    Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them.
    [Show full text]
  • Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border
    PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border † ‡ Ivy A. Rosales,* A. Bernard Collins,* Paula Alves S. do Carmo, Nina Tolkoff-Rubin, R. Neal Smith,* and Robert B. Colvin* Department of *Pathology and ‡Division of Nephrology, Renal Transplantation Program, Massachusetts General Hospital, Boston, Massachusetts; and †Centro Especializado em Anatomia Patologica, Belo Horizonte, Minas Gerais, Brazil ABSTRACT Immune complex tubulointerstitial nephritis due to antibodies to brush border associated with focal tubulitis. Interstitial antigens of the proximal tubule has been demonstrated experimentally and rarely in fibrosis and tubular atrophy were diffuse humans. Our patient developed ESRD and early recurrence after transplantation. and present in 70% of the cortex. No gi- IgG and C3 deposits were conspicuous in the tubular basement membrane of antcellswereseen.Anarteryshowed proximal tubules, corresponding to deposits observed by electron microscopy. mild intimal fibrosis. Few IgG4-positive Rare subepithelial deposits were found in the glomeruli. The patient had no plasma cells were detected in the intersti- evidence of SLE and had normal complement levels. Serum samples from the tium (mean of 2 per high-power field). patient reacted with the brush border of normal human kidney, in contrast with the Immunofluorescence (IF) showed negative results with 20 control serum samples. Preliminary characterization of widespread granular deposits along the the brush border target antigen excluded megalin, CD10, and maltase. We postulate proximal tubular basement membrane that antibodies to brush border antigens cause direct epithelial injury, accumulate in (TBM), which stained for IgG (3+), C3 the tubular basement membrane, and elicit an interstitial inflammatory response.
    [Show full text]
  • LECTURE: 10 Title: IMMUNOLOGICAL MECHANISM in TISSUE DAMAGE TYPE-III IMMUNE-COMPLEX MEDIATED HYPERSENSITIVITY
    LECTURE: 10 Title: IMMUNOLOGICAL MECHANISM IN TISSUE DAMAGE TYPE-III IMMUNE-COMPLEX MEDIATED HYPERSENSITIVITY LEARNING OBJECTIVES: The student should be able to: • Define type III hypersensitivity reactions. • Identify the role of the immune complex in type III reactions, and indicate which cause more damage small or large immune complexes, and locate the possible deposition of each complex. • Compare type III and type I reactions. • List some of the immune complex diseases: - Autoimmune diseases: ♦ Systemic lupus erythematosus (SLE). ♦ Rheumatoid arthritis (RA). ♦ Hyperthyroidism. - Infectious agents: ♦ Infectious mononucleosis. ♦ Meningitis. ♦ Viral hepatitis (Chronic stage). ♦ Poststreptococcal glomerulonephritis. ♦ Streptokinase (bacterial enzymes) in cardiac patients. - Drugs: ♦ Sulfonamides + penicillin. • Determine either type III reactions act locally or systematically. • Explain the mechanism of local immune complex deposition and give one example. • Explain the mechanism of generalized immune complex deposition, and give one example. • Explain the main target organ (s) for type III reactions. • Describe the mechanism of activation of type III reaction. • List a diagnostic method, and some examples of clinical features of type III such as: - Arthus reactions (Local immune complex-deposition). - Serum sickness (Systemic immune complex-deposition). LECTURE REFRENCE: 1. TEXTBOOK: ROITT, BROSTOFF, MALE IMMUNOLOGY. 6th edition. Chapter 23. pp. 357-367. 2. HANDOUT. Hypersensitivity – Type III Immune complexes are formed every time antibody meets antigen and are removed by the mononuclear phagocyte system following complement activation. Persistence of antigen from continued infection or in autoimmune disease can lead to immune-complex disease. Immune complexes can form both in the circulation, leading to systemic disease, and at local sites such as the lung. Complement helps to disrupt antigen-antibody bonds and keeps immune complexes soluble.
    [Show full text]
  • Fcγ Receptors As Regulators of Immune Responses
    REVIEWS Fcγ receptors as regulators of immune responses Falk Nimmerjahn* and Jeffrey V. Ravetch‡ Abstract | In addition to their role in binding antigen, antibodies can regulate immune responses through interacting with Fc receptors (FcRs). In recent years, significant progress has been made in understanding the mechanisms that regulate the activity of IgG antibodies in vivo. In this Review, we discuss recent studies addressing the multifaceted roles of FcRs for IgG (FcγRs) in the immune system and how this knowledge could be translated into novel therapeutic strategies to treat human autoimmune, infectious or malignant diseases. Regulatory T cells A productive immune response results from the effec- of antigenic peptides that are presented on the surface A T cell subset that is capable tive integration of positive and negative signals that of DCs to cytotoxic T cells, T helper cells, and regulatory of suppressing the activity have an impact on both innate and adaptive immune T cells. Thus, FcγRs are involved in regulating a multitude of other antigen-specific T cells cells. When positive signals dominate, cell activation of innate and adaptive immune responses, which makes including autoreactive T cells. Depletion of regulatory and pro-inflammatory responses ensue, resulting in the them attractive targets for the development of novel T cells results in the loss of elimination of pathogenic microorganisms and viruses. immunotherapeutic approaches (FIG. 1). peripheral tolerance and the In the absence of such productive stimulation, cell activa- In this Review, we summarize our current under- development of autoimmune tion is blocked and active anti-inflammatory responses standing of the role of different members of the FcγR disease.
    [Show full text]
  • I M M U N O L O G Y Core Notes
    II MM MM UU NN OO LL OO GG YY CCOORREE NNOOTTEESS MEDICAL IMMUNOLOGY 544 FALL 2011 Dr. George A. Gutman SCHOOL OF MEDICINE UNIVERSITY OF CALIFORNIA, IRVINE (Copyright) 2011 Regents of the University of California TABLE OF CONTENTS CHAPTER 1 INTRODUCTION...................................................................................... 3 CHAPTER 2 ANTIGEN/ANTIBODY INTERACTIONS ..............................................9 CHAPTER 3 ANTIBODY STRUCTURE I..................................................................17 CHAPTER 4 ANTIBODY STRUCTURE II.................................................................23 CHAPTER 5 COMPLEMENT...................................................................................... 33 CHAPTER 6 ANTIBODY GENETICS, ISOTYPES, ALLOTYPES, IDIOTYPES.....45 CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION..................................................................53 CHAPTER 8 GENETIC BASIS OF ANTIBODY DIVERSITY...................................61 CHAPTER 9 IMMUNOGLOBULIN BIOSYNTHESIS ...............................................69 CHAPTER 10 BLOOD GROUPS: ABO AND Rh .........................................................77 CHAPTER 11 CELL-MEDIATED IMMUNITY AND MHC ........................................83 CHAPTER 12 CELL INTERACTIONS IN CELL MEDIATED IMMUNITY ..............91 CHAPTER 13 T-CELL/B-CELL COOPERATION IN HUMORAL IMMUNITY......105 CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES...............................................................111
    [Show full text]
  • The Immune System and Kidney Disease: Basic Concepts and Clinical Implications
    REVIEWS The immune system and kidney disease: basic concepts and clinical implications Christian Kurts1, Ulf Panzer2, Hans-Joachim Anders3 and Andrew J. Rees4 Abstract | The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system. Considerable progress has been made both in under- role of the cellular immune responses that drive renal 1Institutes of Molecular standing the basic immune mechanisms of kidney disease. Moreover, we summarize recent discoveries Medicine and Experimental disease and in translating these findings to clinical about complement- and antibody-mediated nephritis, Immunology (IMMEI), therapies. Sophisticated animal studies combined and we discuss kidney pathologies that are mediated Rheinische Friedrich- with the analysis of clinical samples have led to a pre- by renal autoantigen-specific antibodies, especially those Wilhelms-Universität, cise knowledge of the autoimmune targets and of the that are induced by crossreactive microorganism-specific Sigmund-Freud-Str. 25, 53105 Bonn, Germany. mechanisms responsible for kidney injury.
    [Show full text]
  • Brief History of Important Immunologic Discoveries and Developments
    Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1798 Cowpox vaccination Edward Jenner 1866 Wound disinfection Joseph Lister 1876 Discovery of B. antracis, foundation of Robert Koch bacteriology 1880 Discovery of attenuated vaccine by Louis Pasteur invitro passages 1883 Phagocytosis, cellular immunity theory Elie I. I. Metchnikoff 1888 Discovery of bacterial toxins P. P. Emile Roux and Alexandre E. J. Y ersin 1890 Discovery of antitoxins, foundation of Emil A. von Behring and serotherapy Shibasaburo Kitasato 1894 Immunologic bacteriolysis Richard F. J. Pfeiffer and Vasily I. Isaeff 1894 Discovery of antibody and complement Jules J.B. V. Bordet activity as the active factors in bacteriolysis 1896 Discovery of specific agglutination Herbert E. Durham and Max von Gruber 1896 Agglutination test for the diagnosis of Georges F. I. Widal and typhoid (Widal test) Jean-Marie-Athanase Sicard 1900 Formulation of side-chain theory of anti- Paul Ehrlich body formation 1900 Discovery of A, B, 0 blood groups Karl Landsteiner 1900 Development of complement fixation Jules J.B. V. Bordet and reaction Octave Gengou 1902 Discovery of anaphylaxis Charles R. Richet and Paul Portier 1903 Local anaphylaxis due to antibody- Nicholas M. Arthus antigen complex: Arthus reaction 1903 Discovery of opsonization Almroth E. Wright and Steward R. Douglas 440 Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1905 Description of serum sickness Clemens von Pirquet and Bela Schick 1910 Introduction of salvarsan, later neo- Paul Ehrlich and Sahachiro Hata salvarsan, foundation of chemotherapy of infections 1910 Development of anaphylaxis test William Schultz (Schultz-Dale) 1914 Formulation of genetic theory of tumor Clarence C.
    [Show full text]
  • Role of Circulating Immune Complexes in Renal Diseases
    J Clin Pathol: first published as 10.1136/jcp.34.11.1214 on 1 November 1981. Downloaded from J Clin Pathot 1981 ;34:1214-1222 Role of circulating immune complexes in renal diseases ROLAND J LEVINSKY From the Department of Immunology, Institute of Child Health, 30 Guilford Street, London WCJ The elimination of a foreign antigen is a function of induced by repeated antigen administration.7 The the antibody, complement and phagocyte systems. most widely quoted experimental model of immune When an immune complex is formed in the circu- complex injury is serum sickness, in which the lation, clearance is effected by cells of the reticulo- animal develops nephritis and vasculitis due to endothelial system. Macrophages and polymorpho- deposition of immune complexes 8-10 days after the nuclear cells have both IgG Fc and C3b complement injection of antigen. When the antigen is still in receptors so that opsonisation by either the classical excess of antibody within the circulation, the small or the alternative pathway of complement activation immune complexes formed remain in solution but facilitates antigen elimination. This system normally can become trapped in vessel walls at sites of provides a most efficient protection against disease, turbulence or at capillary membranes where filtration since man is continually challenged by a variety of occurs. Tissue damage at these sites results from the inhaled and ingested antigens. biological effects of complexes which activate the Why then does a normally protective system complement system, resulting in immune adherence,copyright. become self-damaging, resulting in immune complex polymorph chemotaxis, release of lysosomal pro- disease? It is unlikely that most immune complex teolytic enzymes and kinins, and platelet aggregation.
    [Show full text]
  • CUTANEOUS IMMUNE COMPLEX VASCULITIS, SKIN-LIMITED CUTANEOUS IGA OR IGG/IGM VASCULITIS (Formerly Called: Allergic/Hypersensitivity Vasculitis)
    EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY Information Leaflet for Patients CUTANEOUS IMMUNE COMPLEX VASCULITIS, SKIN-LIMITED CUTANEOUS IGA OR IGG/IGM VASCULITIS (Formerly called: Allergic/Hypersensitivity Vasculitis) The aim of this leaflet This leaflet is designed to help you understand more about cutaneous immune complex vasculitis or skin -limited IgA or IgG/IgM vasculitis (formerly called allergic/hypersensitivity vasculitis). It tells you what this condition is, what causes it, and what can be done for treatment. CUTANEOUS What are immunoglobulins (IgA, IgG and IgM)? Immunoglobulins or antibodies are proteins made by the immune system to fight antigens, IMMUNE COMPLEX such as bacteria, viruses, and toxins. The body makes 5 different types of immunoglobulins VASCULITIS, to combat different antigens. Immunoglobulin A (IgA): is found in high concentrations in the mucous membranes, SKIN-LIMITED particularly those lining the respiratory passages and gastrointestinal tract, as well as in CUTANEOUS saliva and tears. Immunoglobulin G (IgG): the most abundant type of antibody, is found in all body fluids and IGA OR IGG/IGM protects against bacterial and viral infections. VASCULITIS Immunoglobulin M (IgM), which is found mainly in the blood and lymph fluid, is the first antibody to be made by the body to fight a new infection. What is allergic vasculitis? In half of cases, a trigger of cutaneous immune complex vasculitis can be identified, Cutaneous immune complex vasculitis, the most common of which include recent usually manifesting as skin -limited IgA or acute infections (eg. upper respiratory tract IgG/IgM vasculitis (formerly called:¨Allergic/ infections, viral hepatitis and HIV infection) hypersensitivity vasculitis) belongs to the or certain medications: antibiotics are cutaneous small-vessel vasculitides, and is a the most common drugs to cause disorder characterized by the inflammation cutaneous immune complex vasculitis, of some small blood vessels located mainly particularly beta-lactams.
    [Show full text]