DOCSLIB.ORG

1. Introduction to Immunology Professor Charles Bangham ([email protected])

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

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. Highly specific to foreign proteins, i.e. antigens recognition of danger signals Cells involved: Cells involved : - Neutrophils (PMN) - T lymphocytes - Macrophages - B lymphocytes - Natural killer (NK) cells - Dendritic cells - Eosinophils - Basophils/mast cells Soluble factors involved Soluble factors involved - Acute-phase proteins - Antibodies - Cytokines - Complement Stimulates the acquired immune response Innate Immunity Anatomical barriers - Skin as a mechanical barrier- keeps out 95% of household germs while IN TACT - Mucus membrane in respiratory and GI tract traps microbes - Cilial propulsion on epithelia cleans lungs of invading microorganisms Physiological barriers - Low PH - Secretion of lysozyme, e.g. in tears - Interferons - Antimicrobial peptides - Complement; responsible for lysing microorganisms Acute-phase inflammatory response An innate response to tissue damage Rise in body temperature, i.e. the fever response This is followed by increased production of a number of proteins (acute-phase proteins), mainly by the liver. Includes: - C-reactive protein - Serum amyloid protein - Mannan-binding lectin C-reactive protein and serum amyloid protein bind to molecules found on the cell wall of some bacteria and fungi- pattern recognition Mannan-binding lectin binds to mannose sugar molecules which are not often found on mammalian cells These molecules are non-specific, but direct phagocytes e.g. macrophages to identify and ingest the infectious agent Cytokines Small proteins that carry messages from one cell to another E.g. to stimulate activation or proliferation of lymphocytes “kick-start”acquired immune response Send messages to other cells, e.g. to kill or secrete 2 MCD Immunology Alexandra Burke-Smith Cells of the innate immune system Granular leukocytes Natural Killer (NK) cells - Identify and kill virus-infected and tumour cells - Complex recognition system- recognise HLA molecule of virus infected cell or tumour, and kill them Macrophages - Mononuclear phagocytes - To main functions: 1. “garbage disposal” - 2. Present foreign cells to immune system Granulocytes Neutrophils Eosinophils Basophils Poluymorphonuclear Bi-lobed nucleus neutrophils (PMN): multi- lobed nucleus 50-70% of circulating WBC 1-3% of circulating WBH <1% of circulating WBC Phagocytic Not phagocytic- release granules containing histamines, serotonin, prostaglandins Required for immune Important in Th2 responses- response to parasites, kick starting acquired helminths and allergic immune reponse responses 3. Define the terms antigen, antibody, B lymphocyte, T lymphocyte, primary and secondary immune responses, and innate and acquired immunity. Acquired/Adaptive Immunity Characteristics Antigen specific Can form memory Requires priming- specific cells help to start the acquired immune response Cellular Immunity: T and B cells Humoral immunity: antibodies Antigens are glycoprotein molecules which react with antibodies or T cells. However not all antigens can induce an immune response in the host: those that can are termed immunogens Antibody molecules can be found in the blood stream and the body fluids and bind specifically to particular molecules termed antigens. They are the acquired component of the humoral immune response.The most basic antibody molecule is bivalent- with two antigen binding sites. Immunoglobulins IgG - 75% of our serum - Crosses placenta, therefore important in protecting newborns - Long serum hal-life - Part of secondary immune respons 3 MCD Immunology Alexandra Burke-Smith - Bivalent- two identical antigen binding sites IgM - 10% of total serum Ig - Complex of 5 linked bivalent monomeric antibodies, therefore 10 identical binding sites- multivalent - Star-like shape - Important in primary immune response - Slightly lower affinity to antigens compared to IgG, which is compensated for by number of binding sites IgA - 2 basic monomers; dimer with secretory piece - Found in body secretions, e.g. mucus membranes in GI tract - Contains a secretory component which protects it from digestive enzymes IgE - Involved in allergic response and the response to helminths - Binds to basophils and mast cells - Triggers release of histamines IgD - Complete function not known A particularly antibody ‘recognizes’ an antigen because that antibody’s binding site it complementary to the EPIPTOPE (region approx 6 amino acids long) on the antigen. This forms the basis of the specificity of antigen recognition. How does an antibody kill a virus? Four important mechanisms: 1. Binds to the virus and prevents attachment to the cell 2. Opsonisation: virus-antibody complex is recognised and phagocytosed by macrophage 3. Complement- mediated lysis of enveloped viruses: cascade of enzymes in the blood which leads to the destruction of cell membranes, and the destruction of the viral envelope 4. Antibody-dependant cell-mediated cytotoxicity (ADCC) mediated by NK-like cells (see earlier for explanation) Cells of the acquired immune system Lymphocytes Agranular leukocytes 20-40% of the circulating WBC 99% of the cells in lymphatic circulation T (thymus-derived) cells - Helper T cells: recognize antigen, help B cells to make antibodies and T cells to kill - Cytotoxic T cells: poisonous to cells,kill cells infected by viruses and intracellular bacteria B (bone marrow-derived) cells - Make antibodies - Have insoluble antigen-binding receptor on its surface. In fact have multiple clones of this receptor; monoclonal antibodies NK (natural killer) cells - See earlier in notes Each subset has distinct cell-surface molecules, e.g. CD4 on helper T-cell which is the receptor for HIV molecules Lymphocyte precursors are produced in the haematopoietic tissue in the bone marrow 4 MCD Immunology Alexandra Burke-Smith T cells are then transported to the thymus, where they undergo THYMAL EDUCATION. Here 95-99% get destroyed as they have the potential to recognise host cells 4. Outline the role of clonal selection in immune responses. Lymphocyte antigen receptors B cell antigen receptor is a membrane-bound antibody, i.e. surface immunoglobulin which binds intact antigens; recognises surface of protein, therefore antigen must be in native conformation Expressed on the T cell surface are 2 protein chains (alpha and beta) which together make the t cell antigen receptor (TCR). This binds to digested antigen fragments. Each antigen receptor binds to an epitope on a different antigen, and is unique to a cell. There are many copies of the receptor on the cell surface The T-cell antigen receptor (TCR) Recognizes complex of antigen peptide and HLA (MHC) molecule HLA (Human leukocyte antigen) binds to little fragments of the pathogen, transports them to the surface so they can be recognized, e.g. so a virus cannot hide inside a host cell. Combination of short peptide from microorganism + HLA = recognition by TCR MHC denotes the Major Histocompatibility Complex (also known as HLA) Generation of clonal diversity in lymphocytes During B and T cell development, random genetic recombinations occur within each cell among multiple copies of immunoglobulin genes (B cells) or TCR genes (T cells). There are parallel genes, but they undergo random splicing and recombination which leads to a large repertoire of antigen receptors These processes generate the diversity of clones of lymphocytes: each clone is specific to a different antigen. Primary Immune Response: clonal selection A typical antigen is recognized by 1 in ~105 naive T cells 98% of T cells are in the lymph circulation and organs; 2% in blood. Antigen binds to surface receptor on the B cell (Ig) or the T cell (TCR) and causes selective expansion of that clone. The receptors which bind with highest affinity to the antigen are selected for, outcompete
Recommended publications
  • Immunology New Orleans, LA Toll Free 888.355.4191 Toll Free Fax 888.355.4192 Krogerspecialtypharmacy.Com

    Immunology New Orleans, LA Toll Free 888.355.4191 Toll Free Fax 888.355.4192 Krogerspecialtypharmacy.Com

    Immunology New Orleans, LA toll free 888.355.4191 toll free fax 888.355.4192 krogerspecialtypharmacy.com Need By Date: _________________________________________________ Ship To: Patient Office Fax Copy: Rx Card Front/Back Clinical Notes Medical Card Front/Back Patient Information Prescriber Information Patient Name Prescriber Name Address Address City State Zip City State Zip Main Phone Alternate Phone Phone Fax Social Security # Contact Person Date of Birth Male Female DEA # NPI # License # Clinical Information Diagnosis: J45.40 Moderate Asthma J45.50 Severe Asthma L20.9 Atopic Dermatitis L50.1 Chronic Idiopathic Urticaria (CIU) Eosinophil Levels J33 Chronic Rhinosinusitis with Nasal Polyposis Other: ________________________________ Dx Code: ___________ Drug Allergies Concomitant Therapies: Short-acting Beta Agonist Long-acting Beta Agonist Antihistamines Decongestants Immunotherapy Inhaled Corticosteroid Leukotriene Modifiers Oral Steroids Nasal Steroids Other: _____________________________________________________________ Please List Therapies Weight kg lbs Date Weight Obtained Lab Results: History of positive skin OR RAST test to a perennial aeroallergen Pretreatment Serum lgE Level: ______________________________________ IU per mL Test Date: _________ / ________ / ________ MD Specialty: Allergist Dermatologist ENT Pediatrician Primary Care Prescription Type: Naïve/New Start Restart Continued Therapy Pulmonologist Other: _________________________________________ Last Injection Date: _________ / ________
  • The Ligands for Human Igg and Their Effector Functions

    The Ligands for Human Igg and Their Effector Functions

    antibodies Review The Ligands for Human IgG and Their Effector Functions Steven W. de Taeye 1,2,*, Theo Rispens 1 and Gestur Vidarsson 2 1 Sanquin Research, Dept Immunopathology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] 2 Sanquin Research, Dept Experimental Immunohematology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected] Received: 26 March 2019; Accepted: 18 April 2019; Published: 25 April 2019 Abstract: Activation of the humoral immune system is initiated when antibodies recognize an antigen and trigger effector functions through the interaction with Fc engaging molecules. The most abundant immunoglobulin isotype in serum is Immunoglobulin G (IgG), which is involved in many humoral immune responses, strongly interacting with effector molecules. The IgG subclass, allotype, and glycosylation pattern, among other factors, determine the interaction strength of the IgG-Fc domain with these Fc engaging molecules, and thereby the potential strength of their effector potential. The molecules responsible for the effector phase include the classical IgG-Fc receptors (FcγR), the neonatal Fc-receptor (FcRn), the Tripartite motif-containing protein 21 (TRIM21), the first component of the classical complement cascade (C1), and possibly, the Fc-receptor-like receptors (FcRL4/5). Here we provide an overview of the interactions of IgG with effector molecules and discuss how natural variation on the antibody and effector molecule side shapes the biological activities of antibodies. The increasing knowledge on the Fc-mediated effector functions of antibodies drives the development of better therapeutic antibodies for cancer immunotherapy or treatment of autoimmune diseases.
  • Lactoferrin and Its Detection Methods: a Review

    Lactoferrin and Its Detection Methods: a Review

    nutrients Review Lactoferrin and Its Detection Methods: A Review Yingqi Zhang, Chao Lu and Jin Zhang * Department of Chemical and Biochemical Engineering, University of Western Ontario, London, ON N6A 5B9, Canada; [email protected] (Y.Z.); [email protected] (C.L.) * Correspondence: [email protected] Abstract: Lactoferrin (LF) is one of the major functional proteins in maintaining human health due to its antioxidant, antibacterial, antiviral, and anti-inflammatory activities. Abnormal levels of LF in the human body are related to some serious diseases, such as inflammatory bowel disease, Alzheimer’s disease and dry eye disease. Recent studies indicate that LF can be used as a biomarker for diagnosis of these diseases. Many methods have been developed to detect the level of LF. In this review, the biofunctions of LF and its potential to work as a biomarker are introduced. In addition, the current methods of detecting lactoferrin have been presented and discussed. We hope that this review will inspire efforts in the development of new sensing systems for LF detection. Keywords: lactoferrin; biomarkers; immunoassay; instrumental analysis; sensor 1. Introduction Lactoferrin (known as lactotransferrin, LF), with a molecular weight of about 80 kDa, is a functional glycoprotein, which contains about 690 amino acid residues. It was first isolated from bovine milk by Sorensen in 1939 and was first isolated from human milk by Citation: Zhang, Y.; Lu, C.; Zhang, J. Johanson in 1960 [1,2]. The three-dimensional structure of LF has been unveiled by high Lactoferrin and Its Detection resolution X-ray crystallographic analysis, and it consists of two homologous globular lobes Methods: A Review.

  • IFM Innate Immunity Infographic

    UNDERSTANDING INNATE IMMUNITY INTRODUCTION The immune system is comprised of two arms that work together to protect the body – the innate and adaptive immune systems. INNATE ADAPTIVE γδ T Cell Dendritic B Cell Cell Macrophage Antibodies Natural Killer Lymphocites Neutrophil T Cell CD4+ CD8+ T Cell T Cell TIME 6 hours 12 hours 1 week INNATE IMMUNITY ADAPTIVE IMMUNITY Innate immunity is the body’s first The adaptive, or acquired, immune line of immunological response system is activated when the innate and reacts quickly to anything that immune system is not able to fully should not be present. address a threat, but responses are slow, taking up to a week to fully respond. Pathogen evades the innate Dendritic immune system T Cell Cell Through antigen Pathogen presentation, the dendritic cell informs T cells of the pathogen, which informs Macrophage B cells B Cell B cells create antibodies against the pathogen Macrophages engulf and destroy Antibodies label invading pathogens pathogens for destruction Scientists estimate innate immunity comprises approximately: The adaptive immune system develops of the immune memory of pathogen exposures, so that 80% system B and T cells can respond quickly to eliminate repeat invaders. IMMUNE SYSTEM AND DISEASE If the immune system consistently under-responds or over-responds, serious diseases can result. CANCER INFLAMMATION Innate system is TOO ACTIVE Innate system NOT ACTIVE ENOUGH Cancers grow and spread when tumor Certain diseases trigger the innate cells evade detection by the immune immune system to unnecessarily system. The innate immune system is respond and cause excessive inflammation. responsible for detecting cancer cells and This type of chronic inflammation is signaling to the adaptive immune system associated with autoimmune and for the destruction of the cancer cells.
  • Discussion of Natural Killer Cells and Innate Immunity

    Discussion of Natural Killer Cells and Innate Immunity

    Discussion of natural killer cells and innate immunity Theresa L. Whiteside, Ph.D. University of Pittsburgh Cancer Institute Pittsburgh, PA 15213 Myths in tumor immunology • Cancer cells are ignored by the immune system • Immune responses are directed only against “unique” antigens expressed on tumor cells • Tumor-specific T cells alone are sufficient for tumor regression • Tumor are passive targets for anti-tumor responses Tumor/Immune Cells Interactions Tumor cell death C G DC M TUMOR NK Th B Tc Ab Ag Ag/Ab complex NK cells as anti-tumor effectors • LGL, no TCR, express FcγRIII, other activating receptors and KIRs • Spare normal cells but kill a broad range of tumor cells ex vivo by at least two different mechanisms • Produce a number of cytokines (IFN-γ, TNF-α) • Constitutively express IL-2Rβγ and rapidly respond to IL-2 and also to IL-15 and IFNα/β • Regulated by a balance of inhibitory receptors specific for MHC class I antigens and activating signals • NK-DC interactions at sites of inflammation Heterogeneity of human NK cells • Every NK cell expresses at least one KIR that recognizes a self MHC class I molecule • Two functionally distinct subsets: 1) 90% CD56dimCD16bright , highly cytotoxic, abundant KIR expression, few cytokines 2) 10% CD56brightCD16dim/neg, produce cytokines, poorly cytotoxic, low KIR expression Expression of activating and inhibitory receptors on NK cells Interaction with CD56 Interaction with MHC ligands non-MHC ligands KIR CD16 CD2 CD94/NKG2A/B β2 NKp46, 44, 30 CD94/NKG2C/E NK Cell 2B4 NKG2D Lair1 LIR/ILT A
  • C3b Catalog Number: A114 Sizes Available

    C3b Catalog Number: A114 Sizes Available

    Name: C3b Catalog Number: A114 Sizes Available: 250 µg/vial Concentration: 1.0 mg/mL (see Certificate of Analysis for actual concentration) Form: Liquid Purity: >90% by SDS-PAGE Buffer: 10 mM sodium phosphate, 145 mM NaCl, pH 7.3 Extinction Coeff. A280 nm = 1.03 at 1.0 mg/mL Molecular Weight: 176,000 Da (2 chains) Preservative: None, 0.22 µm filtered Storage: -70oC or below. Avoid freeze/thaw. Source: Normal human serum (shown by certified tests to be negative for HBsAg and for antibodies to HCV, HIV-1 and HIV-II). Precautions: Use normal precautions for handling human blood products. Origin: Manufactured in the USA. General Description C3b is derived from native C3 upon cleavage and release of C3a. It is prepared by cleavage with the alternative pathway C3 convertase. This is important because only a single bond in C3 is cleaved by the native convertase, while cleavage by other proteases, such as trypsin, results in multiple cleavages at many other sites in the protein. Native human C3b is a glycosylated (~2.8%) polypeptide containing two disulfide-linked chains. C3b is central to the function of all three pathways of complement (Law, S.K.A. and Reid, K.B.M. (1995)). Initiation of each pathway generates proteolytic enzyme complexes (C3 convertases) which are bound to the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. For a brief time (~60 µs) this nascent C3b is capable of reacting with and covalently coupling to hydroxyl groups on the target surface.
  • We Work at the Intersection of Immunology and Developmental Biology

    We Work at the Intersection of Immunology and Developmental Biology

    Development and Homeostasis of Mucosal Tissues U934/UMR3215 – Genetics and Developmental Biology Pedro Hernández Chef d'équipe [email protected] We work at the intersection of immunology and developmental biology. Our primary goal is to understand how immune responses impact the development, integrity and function of mucosal tissue layers, such as the intestinal epithelium, during homeostasis and upon different types of stress, including infections. To study these questions we exploit the advantages of the zebrafish model such as ex utero and rapid development, transparency, large progeny, and simple genetic manipulation. We combine live imaging, flow cytometry, single-cell transcriptomics, and models inducing mucosal stress, including pathogenic challenges. Our research can be subdivided into three main topics: 1) Protection of intestinal epithelial integrity since early development: Epithelial cells are at the core of intestinal organ function. They are in charge of absorbing nutrients and water, and at the same time constitute a barrier for potential pathogens and harmful molecules. Epithelial cells perform all these functions before full development of the immune system, which promotes epithelial barrier function upon injury. We study how robust epithelial integrity is achieved prior and after maturation of the intestinal immune system, with a focus on the function of mucosal cytokines. 2) Epithelial-leukocyte crosstalk throughout development: Intestines become vastly populated by leukocytes after exposure to external cues from diet and colonization by the microbiota. We have recently reported the existence and diversity of zebrafish innate lymphoid cells (ILCs), a key component of the mucosal immune system recently discovered in mice and humans. ILCs mediate immune responses by secreting cytokines such as IL-22 which safeguards gut epithelial integrity.
  • Activation Regulates Alternative Pathway Complement Necrotic

    Activation Regulates Alternative Pathway Complement Necrotic

    Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation This information is current as of September 27, 2021. Wei Xu, Stefan P. Berger, Leendert A. Trouw, Hetty C. de Boer, Nicole Schlagwein, Chantal Mutsaers, Mohamed R. Daha and Cees van Kooten J Immunol 2008; 180:7613-7621; ; doi: 10.4049/jimmunol.180.11.7613 Downloaded from http://www.jimmunol.org/content/180/11/7613 References This article cites 56 articles, 27 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/180/11/7613.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Properdin Binds to Late Apoptotic and Necrotic Cells Independently of C3b and Regulates Alternative Pathway Complement Activation1,2 Wei Xu,* Stefan P. Berger,* Leendert A.
  • Monoclonal Antibody Playbook

    Monoclonal Antibody Playbook

    Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide Outpatient administration guide for healthcare providers 2 SEPTEMBER 2021 1 Introduction to COVID-19 Monoclonal Antibody Therapy 2 Overview of Emergency Use Authorizations 3 Site and Patient Logistics Site preparation Patient pathways to monoclonal administration 4 Team Roles and Responsibilities Leadership Administrative Clinical Table of 5 Monoclonal Antibody Indications and Administration Indications Contents Preparation Administration Response to adverse events 6 Supplies and Resources Infrastructure Administrative Patient Intake Administration 7 Examples: Sites of Administration and Staffing Patterns 8 Additional Resources 1 1. Introduction to Monoclonal Therapy 2 As of 08/13/21 Summary of COVID-19 Therapeutics 1 • No Illness . Health, no infections • Exposed Asymptomatic Infected . Scope of this Implementation Guide . Not hospitalized, no limitations . Monoclonal Antibodies for post-exposure prophylaxis (Casirivimab + Imdevimab (RGN)) – EUA Issued. • Early Symptomatic . Scope of this Implementation Guide . Not hospitalized, with limitations . Monoclonal Antibodies for treatment (EUA issued): Bamlanivimab + Etesevimab1 (Lilly) Casirivimab + Imdevimab (RGN) Sotrovimab (GSK/Vir) • Hospital Adminission. Treated with Remdesivir (FDA Approved) or Tocilizumab (EUA Issued) . Hospitalized, no acute medical problems . Hospitalized, not on oxygen . Hospitlaized, on oxygen • ICU Admission . Hospitalized, high flow oxygen, non-invasive ventilation
  • Eosinophil Cytolysis and Release of Cell-Free Granules

    Eosinophil Cytolysis and Release of Cell-Free Granules

    CORRESPONDENCE LINK TO ORIGINAL ARTICLE LINK TO INITIAL CORRESPONDENCE to determine what conditions in vivo favour piecemeal degranulation and what condi- Eosinophil cytolysis and release of tions promote cytolysis (with or without ‘net’ formation) and release of intact granules. cell-free granules There are several strong recent reviews cover- ing mechanisms of degranulation, including 10 Helene F. Rosenberg and Paul S. Foster those written by Neves and Weller , and Lacy and Moqbel11, for those seeking greater insight into this important and evolving field. We are grateful for an excellent oppor- The results of eosinophil cytolysis — Helene F. Rosenberg is in the Inflammation tunity to expand on our recent Review specifically, the release of intact granules — Immunobiology Section, National Institute of Allergy (Eosinophils: changing perspectives in are not new findings. There have been many and Infectious Diseases, National Institutes of Health, health and disease. Nature Rev. Immunol. reports of free granules in tissues found in Bethesda, Maryland 20892, USA. 13, 9–22 (2013))1 that has been provided by conjunction with eosinophil-associated dis- Paul S. Foster is at the Priority Research Center the correspondence from Carl Persson and eases, including allergic rhinitis, bronchial for Asthma and Respiratory Diseases, Hunter Medical Research Institute and School of Lena Uller (Primary lysis of eosinophils asthma, atopic dermatitis, urticaria and Biomedical Sciences and Pharmacy, Faculty of Health, 7 as a major mode of activation of eosino- eosinophilic esophagitis . However, it was University of Newcastle, Newcastle, New South Wales, phils in human diseased tissues. Nature not clear what role these granules had, if any, 2300, Australia.
  • Binding and the Effect of the Red Kidney Bean Lectin, Phytohaemagglutinin, In

    Binding and the Effect of the Red Kidney Bean Lectin, Phytohaemagglutinin, In

    Downloaded from https://www.cambridge.org/core British Journal of Nutrition (2006), 95, 105–115 DOI: 10.1079/BJN20051612 q The Authors 2006 Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in . IP address: the gastrointestinal tract of suckling rats 170.106.202.58 Ann Linderoth1*, Olena Prykhod’ko1, Bo Ahre´n2, Frida Fa˚k1, Stefan G. Pierzynowski1 and Bjo¨rn R. Westro¨m1 1Department of Cell and Organism Biology, Lund University, Helgonava¨gen 3B, SE-223 62 Lund, Sweden , on 2Department of Medicine, University Hospital, Lund University, Lund, Sweden 29 Sep 2021 at 02:15:37 (Received 7 April 2005 – Revised 8 July 2005 – Accepted 17 July 2005) Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14 d old, were fed a single dose , subject to the Cambridge Core terms of use, available at of PHA (0·05 mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3 d after treatment. Initially, at 1–24 h, the PHA bound along the gut mucosal lining, resulting in dis- turbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3 d, the PHA binding had declined, and an uptake by enterocytes was observed.
  • The Essential Role of Anxa2 in Langerhans Cell Birbeck Granules Formation

    The Essential Role of Anxa2 in Langerhans Cell Birbeck Granules Formation

    cells Article The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation Shantae M. Thornton 1, Varsha D. Samararatne 1, Joseph G. Skeate 1 , Christopher Buser 2, Kim P. Lühen 3, Julia R. Taylor 1, Diane M. Da Silva 3,4 and W. Martin Kast 1,3,4,* 1 Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA; [email protected] (S.M.T.); [email protected] (V.D.S.); [email protected] (J.G.S.); [email protected] (J.R.T.) 2 Oak Crest Institute of Science, Monrovia, CA 91016, USA; [email protected] 3 Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; [email protected] (K.P.L.); [email protected] (D.M.D.S.) 4 Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA 90033, USA * Correspondence: [email protected]; Tel.: +1-323-442-3870 Received: 5 March 2020; Accepted: 12 April 2020; Published: 15 April 2020 Abstract: Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM).