Original Article Anemia, Leukocytosis and Eosinophilia in a Resource-Poor
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Cells, Tissues and Organs of the Immune System
Immune Cells and Organs Bonnie Hylander, Ph.D. Aug 29, 2014 Dept of Immunology [email protected] Immune system Purpose/function? • First line of defense= epithelial integrity= skin, mucosal surfaces • Defense against pathogens – Inside cells= kill the infected cell (Viruses) – Systemic= kill- Bacteria, Fungi, Parasites • Two phases of response – Handle the acute infection, keep it from spreading – Prevent future infections We didn’t know…. • What triggers innate immunity- • What mediates communication between innate and adaptive immunity- Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman Jules A. Hoffmann Bruce A. Beutler Ralph M. Steinman 1996 (fruit flies) 1998 (mice) 1973 Discovered receptor proteins that can Discovered dendritic recognize bacteria and other microorganisms cells “the conductors of as they enter the body, and activate the first the immune system”. line of defense in the immune system, known DC’s activate T-cells as innate immunity. The Immune System “Although the lymphoid system consists of various separate tissues and organs, it functions as a single entity. This is mainly because its principal cellular constituents, lymphocytes, are intrinsically mobile and continuously recirculate in large number between the blood and the lymph by way of the secondary lymphoid tissues… where antigens and antigen-presenting cells are selectively localized.” -Masayuki, Nat Rev Immuno. May 2004 Not all who wander are lost….. Tolkien Lord of the Rings …..some are searching Overview of the Immune System Immune System • Cells – Innate response- several cell types – Adaptive (specific) response- lymphocytes • Organs – Primary where lymphocytes develop/mature – Secondary where mature lymphocytes and antigen presenting cells interact to initiate a specific immune response • Circulatory system- blood • Lymphatic system- lymph Cells= Leukocytes= white blood cells Plasma- with anticoagulant Granulocytes Serum- after coagulation 1. -
Hyperleukocytosis (Re)Visited- Is It Case Series Always Leukaemia: a Report of Two Pathology Section Cases and Review of Literature Short Communication
Review Article Clinician’s corner Original Article Images in Medicine Experimental Research Miscellaneous Letter to Editor DOI: 10.7860/JCDR/2020/40556.13409 Case Report Postgraduate Education Hyperleukocytosis (Re)Visited- Is it Case Series always Leukaemia: A Report of Two Pathology Section Cases and Review of Literature Short Communication ASHUTOSH RATH1, RICHA GUPTA2 ABSTRACT Hyperleukocytosis is defined as total leukocyte count of more than 100×109/L. Commonly seen in leukaemic conditions, non- leukaemic causes are usually not encountered and thought of. We report two such non-malignant cases of hyperleukocytosis. A six-year old girl presented with fever, cough and respiratory distress with a leukocyte count of 125.97×109/L. Another case is of a two-month old female infant, who presented with fever and respiratory distress and a leukocyte count of 112.27×109/L. The present case thrives to highlight various possible causes of hyperleukocytosis with an emphasis on non-malignant causes. Also, important complications and management of hyperleukocytosis are discussed. Keywords: Benign, Leukocytosis, Leukostasis CASE REPORT 1 for methicillin-resistant Staphylococcus aureus and was started A six-year-old girl was admitted with complaints of fever, non- on intravenous Vancomycin along with supportive care. Serial productive cough for one week and severe respiratory distress for monitoring of TLC revealed a gradual reduction and it returned to the the past one day. There was no other significant history. On physical baseline of 15×109/L after eight days. The patient was discharged examination, the patient had mild pallor. Respiratory examination after 10 days of hospital stay. -
Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck. -
Hypersensitivity Reactions (Types I, II, III, IV)
Hypersensitivity Reactions (Types I, II, III, IV) April 15, 2009 Inflammatory response - local, eliminates antigen without extensively damaging the host’s tissue. Hypersensitivity - immune & inflammatory responses that are harmful to the host (von Pirquet, 1906) - Type I Produce effector molecules Capable of ingesting foreign Particles Association with parasite infection Modified from Abbas, Lichtman & Pillai, Table 19-1 Type I hypersensitivity response IgE VH V L Cε1 CL Binds to mast cell Normal serum level = 0.0003 mg/ml Binds Fc region of IgE Link Intracellular signal trans. Initiation of degranulation Larche et al. Nat. Rev. Immunol 6:761-771, 2006 Abbas, Lichtman & Pillai,19-8 Factors in the development of allergic diseases • Geographical distribution • Environmental factors - climate, air pollution, socioeconomic status • Genetic risk factors • “Hygiene hypothesis” – Older siblings, day care – Exposure to certain foods, farm animals – Exposure to antibiotics during infancy • Cytokine milieu Adapted from Bach, JF. N Engl J Med 347:911, 2002. Upham & Holt. Curr Opin Allergy Clin Immunol 5:167, 2005 Also: Papadopoulos and Kalobatsou. Curr Op Allergy Clin Immunol 7:91-95, 2007 IgE-mediated diseases in humans • Systemic (anaphylactic shock) •Asthma – Classification by immunopathological phenotype can be used to determine management strategies • Hay fever (allergic rhinitis) • Allergic conjunctivitis • Skin reactions • Food allergies Diseases in Humans (I) • Systemic anaphylaxis - potentially fatal - due to food ingestion (eggs, shellfish, -
Bronchopulmonary Aspergillosis
Thorax: first published as 10.1136/thx.44.11.919 on 1 November 1989. Downloaded from Thorax 1989;44:919-924 Pulmonary eosinophilia with and without allergic bronchopulmonary aspergillosis B J CHAPMAN, S CAPEWELL, R GIBSON, A P GREENING, G K CROMPTON From the Respiratory Unit, Northern General Hospital, Edinburgh ABSTRACT Sixty five patients with pulmonary eosinophilia attending one respiratory unit were reviewed. All had fleeting radiographic abnormalities and peripheral blood eosinophil counts greater than 500 x 106/1. Eighteen had a single episode and 47 recurrent episodes during a median follow up period of 14 years. Thirty three patients had allergic bronchopulmonary aspergillosis on the basis of a positive skin test response to Aspergillusfumigatus, serum precipitins, or culture ofAfumigatus from sputum, or a combination of these. All but seven patients had asthma, six of the seven being in the group who did not have allergic bronchopulmonary aspergillosis. The patients with allergic bronchopulmonary aspergillosis were more often male and had a greater incidence ofasthma and an earlier age of onset of asthma than those without aspergillosis. The patients with aspergillosis had lower mean blood eosinophil counts and more episodes of pulmonary eosinophilia and more commonly had radiographic shadowing that suggested fibrosis or bronchiectasis (20 v 7). Pulmonary eosinophilia associated with allergic bronchopulmonary aspergillosis appears to be a distinct clinical syndrome resulting in greater permanent radiographic abnormality despite lower peripheral blood eosinophil counts. copyright. Introduction ated from secondary and tertiary referral centres, which makes it difficult to estimate the relative The term pulmonary eosinophilia describes a group of frequency of the various underlying conditions. -
The Role of Eosinophils in Parasitic Helminth Infections: Insights from Genetically Modified Mice C.A
Reviews The Role of Eosinophils in Parasitic Helminth Infections: Insights from Genetically Modified Mice C.A. Behm and K.S. Ovington Eosinophilia – an increase in the number of eosinophils in the it has been shown that IL-5, found at high levels in blood or tissues – has historically been recognized as a dis- helminth-infected hosts during the T-helper type 2 tinctive feature of helminth infections in mammals. Yet the (Th2) cytokine-biased immune response, appears to be precise functions of these cells are still poorly understood. important in mucosal immune responses and is re- Many scientists consider that their primary function is pro- sponsible for helminth-induced eosinophilia. IL-5 pre- tection against parasites, although there is little unequivocal sents quite a puzzle for immunologists. It has been in vivo evidence to prove this. Eosinophils are also respon- highly conserved during mammalian evolution – sible for considerable pathology in mammals because they are mouse IL-5, for example, has 71% amino acid identity inevitably present in large numbers in inflammatory lesions with human IL-5 – which suggests it has important associated with helminth infections or allergic conditions. In function(s) that have been selected during evolution. this review, Carolyn Behm and Karen Ovington outline some However, functions exclusive to IL-5 are not numer- of the cellular and biological properties of eosinophils and ous, and none appears to be essential for survival, at evaluate the evidence for their role(s) in parasitic infections. least for mice living in laboratory conditions. In mice, IL-5 controls or influences the development of two Eosinophils or ‘eosinophilic granulocytes’ normally major cell types: the elevated rate of development, mat- comprise only a small fraction (,1–5%) of circulating uration and survival of eosinophils during a Th2 cyto- leukocytes. -
Hypereosinophilic Syndrome Presenting As an Unusual Triad of Eosinophilia, Severe Thrombocytopenia, and Diffuse Arterial Thromboses, with Good Response to Mepolizumab
H & 0 C l i n i C a l C a s e s t u d i e s Hypereosinophilic Syndrome Presenting As an Unusual Triad of Eosinophilia, Severe Thrombocytopenia, and Diffuse Arterial Thromboses, With Good Response to Mepolizumab 1Department of Internal Medicine, University of Iowa 1 Roberto A. Leon-Ferre, MD Hospitals and Clinics, Iowa City, Iowa; 2Division of 2 Catherine R. Weiler, MD, PhD Allergic Diseases and Internal Medicine, Mayo Clinic, Thorvardur R. Halfdanarson, MD3 Rochester, Minnesota; 3Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, Arizona Case Report Complement studies were normal. Fluorescence in situ hybridization (FISH) screening for FIP1L1-PDGFRA A previously healthy 47-year-old man presented with rearrangement was negative. A bone marrow biopsy 3 weeks of bilateral hand numbness, tingling, cyanosis, revealed a normocellular marrow, with marked eosino- and newly onset lower extremity edema and petechiae. philia (47%), adequate numbers of megakaryocytes, and On examination, both hands were dusky, cold, and exqui- no increase in blasts, mast cells, or reticulin fibrosis. Cyto- sitely tender. Bilateral radial pulses and left popliteal pulse genetic studies showed no abnormalities. Peripheral blood were not palpable. No lymphadenopathy, organomegaly, flow cytometry did not identify monoclonal cell popula- or masses were detected. Initial workup revealed severe tions, and no underlying T-cell clone was detected using a eosinophilia and thrombocytopenia (white blood cell T-cell receptor gene rearrangement polymerase chain reac- count, 20.3 × 103/μL; eosinophil count, 10.9 × 103/μL; tion (PCR) study. Serum protein electrophoresis, serum platelet count, 8 × 103/μL), and normal hemoglobin immunofixation electrophoresis, and urine immunofixa- of 15.2 g/dL. -
Eosinophilic Myocarditis Presenting with Hypoactive Delirium and Cardioembolic Stroke
PRACTICE | CASES CPD Eosinophilic myocarditis presenting with hypoactive delirium and cardioembolic stroke Ka Hong Chan MD, Paul Gibson MD n Cite as: CMAJ 2019 October 21;191:E1159-63. doi: 10.1503/cmaj.190669 64-year-old woman with normal baseline functioning presented to hospital with an altered level of conscious- KEY POINTS ness. She had a history of hypertension (perindopril Hypereosinophilic syndrome is a rare condition manifested by 8 mg/d),A gout (allopurinol 200 mg/d) and anxiety (sertraline • hypereosinophilia with ensuing end-organ damage secondary 100 mg/d). She was brought to the hospital by her husband to tissue infiltration and inflammation by these cells; cardiac because of a 3-day history of being in a hypoactive state with uri- involvement from hypereosinophilic syndrome is known as nary and stool incontinence. Her husband reported no preceding eosinophilic myocarditis. infectious, allergic or constitutional symptoms. Family history • The pathophysiology of eosinophilic myocarditis is characterized and rheumatologic review of systems were noncontributory, and by 3 phases: acute necrosis (asymptomatic), thrombosis the patient had no recent history of rashes. There had been no (presents with secondary embolic phenomenon) and fibrosis (most common presentation; presents with cardiomyopathy). out-of-country travel in the preceding 2 years. Treatment of eosinophilic myocarditis relies on elucidating the On admission, the patient’s temperature was 36.3°C, she had a • underlying cause of eosinophilia, which can be broadly regular heart rate of 103 beats/min, her blood pressure was categorized as idiopathic, hypersensitivity, rheumatologic, 128/78 mm Hg and oxygen saturation was 95% on room air. -
Leukocytosis & Lymphocytosis
Leukocytosis Leukocytosis >11 (Repeated) Blood Smear AND History & EMERGENT REFERRAL Refer to Blasts on Smear Physical Exam Lymphocytes >4 Page Hematologist On-Call Lymphocytosis Algorithm Include nodes and spleen Myeloid Cells Basophils Monocytes Neutrophils Eosinophils CONCERNING FEATURES CONCERNING FEATURES CONCERNING FEATURES » Count >2 or increasing, or persistent » Count >50 » Count >2 or increasing or persistent » Not explained by infection » Promyelocytes and myelocytes » Dysplasia YES » Dysplasia » Dysplasia YES » Anemia » Immature forms » Basophilia » New organ damage » Anemia/thrombo-cytopenia » Splenomegaly » NOT explained by infection, allergies » Splenomegaly » NOT associated with acute infection or collagen vascular disease NO NO NO Consider Consider » Cancer Reactive Causes » drugs NO » Collagen VD YES e.g. Infection / inflammation, NO NO » Infections YES » Chronic infection autoimmune, drugs esp. steroids » Allergies » Marrow recovery » Collagen Vascular Disease Refer to Hematology Treat and Observe for recovery Refer to Hematology Treat and Observe for recovery © Blood Disorder Day Pathways are subject to clinical judgement and actual practice patterns may not always follow the proposed steps in this pathway. Lymphocytosis Lymphocytosis >4 (Repeated) Concerning Features “Reactive” Lymphocytes Asymptomatic » Lymphocytes >30 Patient symptoms of infection or acute illness » Hgb <100 » Night sweats/ weight loss » Splenomegaly Flow Cytometry AND Flow Cytometry IF PERSISTENT Work-up for secondary causes »Immunization »Viral -
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 -
Persistent Eosinophilia Is a Challenging Problem
DOI: 10.26717/BJSTR.2017.01.000244 Nahla A M Hamed. Biomed J Sci & Tech Res ISSN: 2574-1241 Editorial Open Access Persistent Eosinophilia is a Challenging Problem Nahla AM Hamed* Professor of Hematology, Faculty of Medicine, Alexandria University, Egypt Received: July 25, 2017; Published: August 01, 2017 *Corresponding author: Nahla AM Hamed, Professor of Hematology, Faculty of Medicine, Alexandria University, Egypt Abstract 9 HE is defined as >1.5 x 10 /L eosinophils in the blood on 2 examinations (interval >1 mo) and/or tissue HE defined by: eosinophils percentage in BM section exceeding 20% of all nucleated cells; and/or extensive eosinophilic tissue infiltration by pathologist opinion; and/or presenceAbbreviations: of marked deposition of eosinophil granule proteins (in the absence or presence of major tissue eosinophils infiltration). AEC: absolute eosinophil count; HE: Hypereosinophilia; ABPA: Allergic Bronchopulmonary Aspergillosis; B-ALL: Acute B-cell lymphoblastic leukemia; GVHD: Graft-Versus-Host Disease; BM: Bone Marrow; PB: Peripheral Blood; IL5: Interleukin 5; AML: Acute Myeloid Leukemia; LV: Lymphocytic Variant; Th2:T-cells have a helper type 2; EPPER: Eosinophilic, polymorphic, and pruritic Eruption Associated with Radiotherapy; MPN: Myeloproliferative Neoplasm; HES: Hypereosinophilic Syndrome; PDGFRA: Platelet-Derived Growth Factor Receptor Alpha; PDGFRB: Platelet-Derived Growth Factor Receptor Beta; FGFR1: Fibroblast Growth Factor Receptor 1; CEL-NOS: Chronic Eosinophilic Leukemia-Not Otherwise Specified; MDS: Myelodysplastic Syndrome; IgH: Ig Heavy Chain; EBV: Epstein-Barr virus Introduction cystic structures (e.g. hydatid cyst, neurocysticercosis) are unlikely Eosinophilia3 is defined as an AEC >500/μL [1].3 The severity ), and severe to cause eosinophilia [7]. Disseminated coccidioidomycosis and of eosinophilia has3 been arbitrarily divided into mild9 (AEC: 500- aspergillosis (when presenting as ABPA) are well-known fungal 1,500/mm ), moderate (AEC: 1,500-5,000/mm causes of eosinophilia. -
1. Introduction to Immunology Professor Charles Bangham ([email protected])
MCD Immunology Alexandra Burke-Smith 1. Introduction to Immunology Professor Charles Bangham ([email protected]) 1. Explain the importance of immunology for human health. The immune system What happens when it goes wrong? persistent or fatal infections allergy autoimmune disease transplant rejection What is it for? To identify and eliminate harmful “non-self” microorganisms and harmful substances such as toxins, by distinguishing ‘self’ from ‘non-self’ proteins or by identifying ‘danger’ signals (e.g. from inflammation) The immune system has to strike a balance between clearing the pathogen and causing accidental damage to the host (immunopathology). Basic Principles The innate immune system works rapidly (within minutes) and has broad specificity The adaptive immune system takes longer (days) and has exisite specificity Generation Times and Evolution Bacteria- minutes Viruses- hours Host- years The pathogen replicates and hence evolves millions of times faster than the host, therefore the host relies on a flexible and rapid immune response Out most polymorphic (variable) genes, such as HLA and KIR, are those that control the immune system, and these have been selected for by infectious diseases 2. Outline the basic principles of immune responses and the timescales in which they occur. IFN: Interferon (innate immunity) NK: Natural Killer cells (innate immunity) CTL: Cytotoxic T lymphocytes (acquired immunity) 1 MCD Immunology Alexandra Burke-Smith Innate Immunity Acquired immunity Depends of pre-formed cells and molecules Depends on clonal selection, i.e. growth of T/B cells, release of antibodies selected for antigen specifity Fast (starts in mins/hrs) Slow (starts in days) Limited specifity- pathogen associated, i.e.