DOCSLIB.ORG

Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. (3+), and equally for k and l (Figure 1). The TBM deposits stained with IgG1 J Am Soc Nephrol 27: 380–384, 2016. doi: 10.1681/ASN.2015030334 (widespread 3+), IgG2 (focal 2+), and IgG4 (widespread 3+). IgG3 was nega- tive. The glomerular deposits were sparse, and they showed very segmental CLINICAL HISTORY blood cell counts and platelets were nor- staining for IgG and did not stain for the mal. Serologies were negative, including phospholipase-A2 receptor. A 73-year-old man presented with nausea, ANCA, anti–glomerular basement Ultrastructural analysis showed wide- vomiting, and progressive renal failure. membrane (GBM), anti-nuclear anti- spreadamorphouselectron-densedeposits His serum creatinine had increased from body, anti–double-stranded DNA, and within the TBM, sometimes abutting the 1.3 mg/dl to 15.2 mg/dl in the 10 months hepatitis B and C. C3 and C4 levels basal plasma membrane of the tubular before admission. He had a history of were normal. An ultrasound showed cell (Figure 1). Scattered penetrating coronary artery disease, diabetes, and no evidence of a mass, obstruction, or subepithelial deposits were present in a hypertension, and he was taking multi- stenosis. small minority of glomerular capillaries ple medications including omeprazole, without spike formation (Figure 1). The lisinopril, metformin, simvastatin, meto- GBM was diffusely but mildly thickened prolol, aspirin, and insulin. On admission, KIDNEY BIOPSY his BP was 148/78 mmHg. His other vital signs were normal and his physical exam- Ten histologically normal glomeruli were ination was unremarkable. He had no present with no endocapillary hypercellu- Published online ahead of print. Publication date prior history of autoimmune disease and larity or GBM abnormality. There was available at www.jasn.org. no family history of autoimmune or renal prominent diffuse tubular injury mani- diseases. fested by loss of brush borders, blebs, Correspondence: Dr. Ivy A. Rosales, Department of Pathology, Massachusetts General Hospital, 55 Urinalysis showed protein (2+), vacuoles, and regenerative changes. An Fruit Street, Thier 831A, Boston, MA 02114. Email: blood (1+), 3–5 white blood cells per interstitial infiltrate of lymphocytes, [email protected] fi high-power eld, and no casts. His he- plasma cells, and a few eosinophils af- Copyright © 2016 by the American Society of moglobin was 12.6 g/L, although white fected 50%–60% of the cortex (Figure 1), Nephrology 380 ISSN : 1046-6673/2702-380 J Am Soc Nephrol 27: 380–384, 2016 www.jasn.org PATHOPHYSIOLOGY of the RENAL BIOPSY Figure 1. Native kidney.(A) Mononuclear inflammatoryinterstitial infiltrate with few admixedneutrophilsand eosinophils, tubular atrophy, and normal-looking glomerulus (hematoxylin and eosin staining). (B) Granular IgG staining of TBMs. (C) Amorphous electron-dense deposits along the TBM. (D) Penetrating subepithelial electron-dense deposits along the GBM. Original magnification, 3400 in A and B; 38900 in C and D. (harmonic mean thickness of 602 nm), Lupus serologies remained negative and were detected in the TBM abutting the indicating early diabetic glomerulopathy. complement levels were normal. An allo- proximal tubule basal membrane, similar These findings were interpreted as graft biopsy showed a sparse inflamma- to the native kidney biopsy. These findings immune complex tubulointerstitial ne- tory infiltrate of about 5% of the cortex, were interpreted as recurrent immune phritis (TIN) with minor involvement of composed of lymphocytes, occasional complex TIN. the glomerulus resembling early mem- neutrophils, and rare eosinophils. Loss The patient’s pretransplant and post- branous GN. of brush borders, dilation, and protein transplant sera were tested for anti–brush casts were focally present, but there was border autoantibodies (ABBAs) by indi- no tubulitis. Glomeruli and vessels were rect IF on cryostat sections of normal kid- CLINICAL FOLLOW-UP unremarkable. IF was similar to the native neys at a 1:5 dilution. Strong and selective biopsy, with diffuse granular TBM depos- binding of IgG to the brush border of The patient was treated with steroids but its that stained for IgG (4+), C3 (4+), and proximal tubules was evident without re- remained hemodialysis dependent. He C4d (4+). The glomeruli were negative. activity to the TBM (Figure 2). Control received a deceased donor allograft kidney C4dwasnegativeinperitubularcapillaries. normal human sera (n=20) did not stain 4 years later. The immediate post-transplant The polyoma stain was negative (SV40 brush borders under the same conditions. course was unremarkable and he was large Tantigen). The TBMdeposits stained To seek the antigenic target, double staining maintained on tacrolimus, mycophenolate forIgG1(widespread3+)andwerenega- with the patient’s serum was repeated com- mofetil, and prednisone. tive for IgG2, IgG3, and IgG4. The signif- bined with antibodies to megalin (Figure 3), Seven weeks later, the patient again icance of the difference in IgG subclasses CD10, or maltase. No colocalization was developed nausea and vomiting and his in the native and allograft biopsies is not present (data not shown). serum creatinine level increased (2 mg/dl). clear. Amorphous electron-dense deposits Plasma exchange was initiated, along with intravenous Ig and rituximab, without dramatic benefit. At 45 weeks post-transplant, the patient’sserum creatinine was 3 mg/dl. A repeat allo- graft biopsy showed progression of the TIN, now involving 30% of the cortex, loss of tubular brush borders, and flat- tened epithelial cells and persistent TBM deposits by IF and electron mi- croscopy (Figure 4). C4d was negative in peritubular capillaries and SV40 was negative. Rare subepithelial glomerular deposits were identified. The patient received methylprednisolone pulses, Figure 2. Indirect IF of the patient’s serum on normal human kidney. (A) IgG staining of rituximab, and later belatacept. Serum proximal tubule brush borders. (B) Proximal tubule brush border IgG staining and negative creatinine levels slowly increased to glomerular staining. (C) Control normal serum on normal human kidney. 3.1 mg/dl 2 years post-transplant. J Am Soc Nephrol 27: 380–384, 2016 Anti–Brush Border Antibodies and Nephritis 381 PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org failure.3 The antigenic target remains uncertain, but ABBAs have not been reported. Idiopathic hypocomplementemic TIN is manifested by granular TBM de- posits of IgG and C3 in association with hypocomplementemia. This preferential TBM deposition has been reported in eight cases, all in the setting of low com- plement levels and not associated with SLE or Sjögren’s syndrome. ABBAs have not been reported in this setting.4 Drug-induced TIN with TBM im- Figure 3. Patient IgG-megalin on normalhuman kidney, colocalization by IF. (A) Patient IgG mune complex deposition has been staining on proximal tubule brush borders. (B) Megalin staining on proximal tubule brush rarely documented in association with borders. (C) No evident IgG-megalin colocalization. nonsteroidal anti-inflammatory drugs.5 Polyclonal IgG and C3 TBM deposits are Antibody titers were determined by should be considered in the differential present without glomerular deposits. indirect IF using sera from pretransplant diagnosis (Table 1). Two cases showed giant cell tubulitis and post-transplant immunosuppressive Lupus nephritis is the most common with TBM deposits.6 In both settings, treatment time points. The titer before cause of immune complex deposition in the deposits were postulated to arise kidney transplantation was .1:960. Be- the TBM, occurring in about 60% of from antidrug antibodies or elicited fore
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]
  • 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]
  • Physicochemical and Functional Relationships of Immune Complexes
    0022-202X/ 80/ 7405-0333$02.00/ 0 THE .J OURNAL OF I NVESTIGATIVE DERMATOLOGY, 74 :333-338, 1980 Vol. 74. No. 5 Copyright © 1980 by T he Williams & Wilkins Co. Printed in U. S.A. Physicochemical and Functional Relationships of Immune Complexes MART MANNIK, M.D. Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington, U.S.A . The biological properties of immune complexes depend immune complexes. In any given immune complex the number on the nature of antigens and antibodies comprising of antigen and antibody molecules may vary, depending on the these complexes. The lattice of immune complexes influ­ characteristics of each of the reactants and the nature of the ences t h eir tissue deposition, complement activation, antigen-antibody union. The biological properties of immune and interaction with Fe receptors. The lattice of immune complexes are related to the properties of the molecules forming complexes d epends on the valence of antigens, the anti­ the complexes, as well as the number of reactants in each gen-antibody ratio, the association constant of these complex. reactants and the concentration of antig ~n and antibody. Antigens are defined as substances that interact specifically Kupffer cells effectively remove large-latticed immune with availa ble a ntibodies or sensitized l ymphocytes. The term complexes from the circulation due to their Fe receptors. immunogen, on the other hand, is reserved for a substance that This system is saturable, leading to prolonged circula­ upon administration to a s uitable host will elicit a n immune tion of the complexes a nd enhanced deposition in tissues.
    [Show full text]