DOCSLIB.ORG

The Effect of Lipids from Mycobacterium Bovis on Bovine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Effect of Lipids from Mycobacterium Bovis on Bovine The Effects of Lipids from Mycobacterium bovis on Bovine Innate and Acquired Immune Responses By Christopher Pirson A thesis submitted to the University of Birmingham for the Degree of Doctor of Philosophy Bovine Tuberculosis Research Team Animal Health & Veterinary Laboratories Agency & School of Biosciences University of Birmingham September 2014 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Declaration The work presented in this thesis was carried out in the Bovine TB Research Team at the Animal Health and Veterinary Laboratories Agency KT15 3NB, during the period September 2009 to September 2014. The work in this thesis is original except where acknowledged by references. No portion of the work is being, or has been submitted for a degree, diploma or any other qualification at any other University. ii Published Work Declaration This thesis contains work which has been accepted to and / or published in peer - reviewed journals. Any publications arising from the work presented in this thesis were written and prepared by Christopher Pirson who is listed as the publications primary author and the contributions of other authors to the text in this thesis are not substantial. Thesis content which is similar to that contained in associated peer - reviewed publications is listed below: Pirson et al., (2012) “Differential effects of Mycobacterium bovis - derived polar and apolar lipid fractions on bovine innate immune cells” Veterinary Research 43:54 • Chapter One: pages 6, 10 and 31 • Chapter Two sections: o Preparation of Bacterial Isolates for Lipid Extraction o Extraction of Crude Free Mycobacterial Lipids o Analysis of Lipid Fractions by 2D Thin Layer Chromatography o Preparation of Lipid Antigen Suspensions o Uninfected Cattle o Isolation of Bovine PBMC from Whole Blood + o Isolation of CD14 Monocytes from Bovine PBMC o Generation of Bovine Cultured Monocytes and MDDC o Multiplex Measurement of Cytokine Production o Innate Cell Labelling & Analysis by Flow Cytometry o Mixed Lymphocyte Reaction • Chapter Three, Discussion: page 70 • Chapter Four sections: o Results o Discussion iii Pirson et al., (2015) “Highly purified mycobacterial phosphatidylinositol mannosides drive cell mediated responses and activate NKT cells in cattle” Clinical and Vaccine Immunology 22:2 • Chapter Two sections: o Preparation of Lipid Antigen Suspensions o M. bovis Infected Cattle o Isolation of Bovine PBMC from Whole Blood TM o Measurement of IFNγ by Bovigam ELISA o Lymphocyte Transformation Assay o Lymphocyte Labelling & Analysis by Flow Cytometry • Chapter Six: pages 130, 131 and 137 - 138 Signed: C. Pirson H. M. Vordermeier iv Abstract The interaction between the host and the pathogen is critical in defining the outcome of an infection. For cattle with bovine tuberculosis (BTB), this interaction is likely to occur between antigen presenting cells in the lung and the lipid rich surface of the causative agent Mycobacterium bovis (M. bovis). It is well documented that lipid molecules from mycobacteria are capable of modulating immune responses however previous work has made use of model animal systems or lipids from avirulent bacteria. The aim of this study was to extract lipids from virulent M. bovis and assess any immunomodulatory ability of these molecules in cattle with a view to aiding in the development of control measures for BTB. To this end, lipids were extracted from M. bovis AF 2122/97 and AN5 and the fractions characterised. Upon thin layer chromatography analysis, polar and apolar fractions from both bacterial strains were found to be broadly similar in their lipid constitution although quantitative differences were noted. Lipopeptide was also identified in both polar fractions. Stimulation of bovine antigen presenting cells with the lipid fractions showed polar lipids mediated increases in IL - 10 and IL - 12 production and reductions in cell surface expression of MHCII and CD1b. Further investigation of the polar lipid fraction was performed by subfractionation but no individual lipid could be found responsible for the responses of antigen presenting cells to these subfractions. The ability of the polar and apolar lipid fractions to be recognised by cells of the adaptive immune system was assessed and the polar fraction was found to drive production of IFNγ and strong proliferation of bovine lymphocytes. The role of lipopeptide in the polar fraction was evaluated by enzymatic degradation with Proteinase K and blockade of either MHCII or CD1. While lipopeptide was found to play a role in the generation of lymphocyte responses, these treatments did not abrogate the effects completely suggesting a lipid mediated component as well. Screening of highly purified individual lipid molecules led to the selection of one molecule (AcPIM6), which was found to be capable of driving antigen specific proliferation of NKT cells. v Dedication For the cows… vi Acknowledgements First and foremost, I would like to thank my supervisor at AHVLA, Prof Martin Vordermeier. Martin provided me with both the inspiration and the self - belief that enabled me to undertake this PhD and without his constant support I would not be where I am today. Rarely will you meet a man of such wisdom and international repute who gives their time and knowledge so freely. I also want to recognise the indefatigable encouragement from Dr Gareth Jones, who may not have signed up to supervise a PhD but took on the responsibility with good grace and humour. His scientific knowledge, rigour and attention to detail are aspirational and he helped hammer both the experiments and this thesis into shape. I must also thank Prof Del Besra and his staff at the University, particularly Dr Sid Gurcha who provided much support during my time in Birmingham and without whom the completion of this project would not have been possible. I would also like to express my gratitude to my professional collaborators; particularly Prof Otto Holst from the Research Centre Borstel for supplying both reagents and good advice in equal measure, and Dr Arun Mishra (who I met in Birmingham but is now at NIMR) who provided me with many of his methods for lipid purification. I would be remiss if I didn’t thank Dr Max Bastian who lent his technical assistance and his expertise as well as the methods for Proteinase K digestion of the lipid fractions. My thanks also go to Prof Mark Chambers and the former Tuberculin Production Unit at AHVLA Weybridge for the pellicle of AN5 which enabled this much of the work in this project. vii I am indebted to my colleagues, past and present, at AHVLA Weybridge for their support and (occasionally unenthusiastic) help. To Adam, Bernardo, Phil, Tom, Laura, Ilaria, Gareth, Carmen, Jim, Shelley, Gilly, Stefan, Paul W, Mick, Roland, Paul A, Sonya, Daryan, Emma, Peter, Karen, Krista, Richard, Elihu, Holly, Margot and Penny I offer my heartfelt thanks. Much has happened in the past few years and I wouldn’t have made it through without their friendship, support and (mostly) friendly abuse. A special thanks is reserved for Dr Paul Wheeler whose peace and quiet I shattered by moving into his lab to perform my lipid analysis work and whose brain I picked on a regular basis. Over the past few years I have garnered much support via Twitter. The #PhDchat hashtag has proven a valuable resource and several users have provided me with advice, support and silly things to laugh at. @LunaLevitt, @PayalYokota, @curexcomplex, @jamimmunology, @psyoureanidiot, @_MaddieHoward, @CS_Diamond, @Carly0308 and @Gemgemloulou have all been more helpful than they probably realise. It really only remains for me to thank my future wife Julia and my family; their support and belief has meant a great deal to me and I hope to return the favour one day. viii Table of Contents Declaration ......................................................................................................................................... ii Published Work Declaration .............................................................................................................. iii Abstract .............................................................................................................................................. v Dedication ......................................................................................................................................... vi Acknowledgements .......................................................................................................................... vii Table of Contents .............................................................................................................................. ix List of Figures ................................................................................................................................... xii List of Tables ..................................................................................................................................... xv Publications Associated
Load more

Recommended publications
  • Laboratorium Benaming
    CAT Critically Appraised Topic Title: Primary Immunodeficiencies: towards a rational testing approach Author: Sien Ombelet Supervisor: Edith Vermeulen Search/methodology verified by: Edith Vermeulen Date: 23/05/2021 CLINICAL BOTTOM LINE Primary immunodeficiencies (PID) in children are rare, but early diagnosis is important for appropriate treatment and favorable outcomes. The threshold for thinking of PID should therefore be low, and clinical alarm signs have been well-defined. However, the best strategy for laboratory testing once a PID is clinically suspected, is unclear. In Imelda hospital, the most commonly ordered laboratory tests for suspected PID are full blood count, quantification of immunoglobulins (Ig), measurement of IgG2 (an IgG subclass) and flow cytometry for classification of lymphocytes into B-cells, T-cells and CD4/CD8 positive cells. Less frequently, humoral immune responses to pneumococcal vaccination are assessed. However, it is unclear which clinical signs or symptoms prompt the clinicians to order either of these tests, and whether the diagnostic strategy is optimal for prompt diagnosis of PID. For this CAT, we aim to provide the clinician with evidence-based criteria when to suspect PID and the appropriate testing strategy in these cases, based on clinical presentation and prevalence of these disorders, also taking into account other possible diagnoses. Four “testing protocols” were designed, based on literature review and expert recommendations. These protocols consist of first line, second line and third line tests. First line tests are full blood count, quantification of immunoglobulins and, depending on the clinical presentation, flow cytometry to differentiate lymphocytes and tests to exclude or confirm the presence of other conditions.
    [Show full text]
  • HEG1 Is a Novel Mucin-Like Membrane Protein That Serves As a Diagnostic and Therapeutic Target for Malignant Mesothelioma
    www.nature.com/scientificreports OPEN HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target Received: 28 October 2016 Accepted: 02 March 2017 for malignant mesothelioma Published: 31 March 2017 Shoutaro Tsuji1,*,, Kota Washimi1,2,*, Taihei Kageyama1, Makiko Yamashita1, Mitsuyo Yoshihara1, Rieko Matsuura1, Tomoyuki Yokose2, Yoichi Kameda3, Hiroyuki Hayashi4, Takao Morohoshi5, Yukio Tsuura6, Toshikazu Yusa7, Takashi Sato8, Akira Togayachi8, Hisashi Narimatsu8, Toshinori Nagasaki1,9, Kotaro Nakamoto1,9, Yasuhiro Moriwaki9, Hidemi Misawa9, Kenzo Hiroshima10, Yohei Miyagi1 & Kohzoh Imai1,11 The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. Malignant mesothelioma (MM) is a fatal tumor caused by past exposure to asbestos1. MM victims number ~3,000, 5,000, and 1,300 per year in the United States, Western Europe, and Japan, respectively1,2.
    [Show full text]
  • The Use of in Vitro Systems for Evaluating Immunotoxicity: the Report and Recommendations of an ECVAM Workshop
    Journal of Immunotoxicology ISSN: 1547-691X (Print) 1547-6901 (Online) Journal homepage: https://www.tandfonline.com/loi/iimt20 The Use of In Vitro Systems for Evaluating Immunotoxicity: The Report and Recommendations of an ECVAM Workshop Alessandra Gennari, Masarin Ban, Armin Braun, Silvia Casati, Emanuela Corsini, Jaroslaw Dastych, Jacques Descotes, Thomas Hartung, Robert Hooghe-Peters, Robert House, Marc Pallardy, Raymond Pieters, Lynnda Reid, Helen Tryphonas, Eric Tschirhart, Helga Tuschl, Rob Vandebriel & Laura Gribaldo To cite this article: Alessandra Gennari, Masarin Ban, Armin Braun, Silvia Casati, Emanuela Corsini, Jaroslaw Dastych, Jacques Descotes, Thomas Hartung, Robert Hooghe-Peters, Robert House, Marc Pallardy, Raymond Pieters, Lynnda Reid, Helen Tryphonas, Eric Tschirhart, Helga Tuschl, Rob Vandebriel & Laura Gribaldo (2005) The Use of InVitro Systems for Evaluating Immunotoxicity: The Report and Recommendations of an ECVAM Workshop, Journal of Immunotoxicology, 2:2, 61-83, DOI: 10.1080/15476910590965832 To link to this article: https://doi.org/10.1080/15476910590965832 Published online: 09 Oct 2008. Submit your article to this journal Article views: 798 View related articles Citing articles: 34 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=iimt20 Journal of Immunotoxicology, 2:61–83, 2005 Copyright c Taylor & Francis Inc. ISSN: 1547-691X print / 1547-6901 online DOI: 10.1080/15476910590965832 The Use of In Vitro Systems for
    [Show full text]
  • Fingerprinting Apoptotic Cell Surfaces
    Fingerprinting Apoptotic Cell Surfaces: Alterations of Glycocalyx and Membrane Composition Den Naturwissenschaftlichen Fakultäten der Friedrich-Alexander-Universität Erlangen-Nürnberg zur Erlangung des Doktorgrades vorgelegt von Sandra Franz aus Chemnitz Als Dissertation genehmigt von den Naturwissenschaftlichen Fakultäten der Universität Erlangen-Nürnberg Tag der mündlichen Prüfung: 13.04.2007 Vorsitzender der Prüfungskommision: Prof. Dr. E. Bänsch Erstberichterstatter: Prof. Dr. L. Nitschke Zweitberichterstatter: Prof. Dr. Dr. h.c. J. R. Kalden Drittberichterstatter: Prof. Dr. W. Jahnen-Dechent Danksagung Herrn Prof. Dr. Dr. h.c. J. R. Kalden möchte ich herzlich für die Betreuung der Arbeit und die Bereitstellung eines Arbeitsplatzes am Institut für klinische Immunologie und Rheumatologie danken. Ich erhielt vielseitige Einblicke in diese spannende Wissen- schaftsgebiet. Ebenso möchte ich mich bei Herrn Prof. Dr. G. Schett für die Möglichkeit bedanken, meine Dissertation am Institut für Klinische Immunologie und Rheumatologie fortzuführen und erfolgreich zu beenden. Herzlichen Dank auch an Herrn Prof. Dr. L. Nitschke für die Bereitschaft meine Arbeit von Seiten der Naturwissenschaftlichen Fakultät II zu vertreten. Besonders bedanken möchte ich mich bei Herrn Prof. Dr. Martin Herrmann für die Bereitstellung des sehr interessanten Themas, seine intensive Unterstützung, die vielen Anregungen und zahlreichen sehr ergiebigen Diskussionen. Ich durfte mich stets in allen Themenbereichen seiner Arbeitsgruppe einbringen und erhielt die Möglichkeit auf zahlreichen Kongressen meine Ergebnisse zu präsentieren. Ebenfalls herzlich danken möchte ich Herrn Prof. Dr. W. Jahnen-Dechent für die Übernahme des Drittgutachtens. Mein Dank gilt auch Herrn Dr. R. E. Voll, Herrn Prof. Dr. H.-M. Jäck und Herrn Prof. Dr. L. Nitschke für die guten Kooperationen, die zahlreichen wissenschaftlichen Diskussionen und für das stete Interesse am Verlauf meiner Arbeit.
    [Show full text]
  • CLEC7A/Dectin-1 Verringert Die Immunantwort Gegen Sterbende Und Tote Zellen)
    CLEC7A/Dectin-1 attenuates the immune response against dying and dead cells (CLEC7A/Dectin-1 verringert die Immunantwort gegen sterbende und tote Zellen) Der Naturwissenschaftlichen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg zur Erlangung des Doktorgrades Dr. rer. nat. vorgelegt von Connie Hesse aus Eberswalde-Finow Als Dissertation genehmigt von der Naturwissenschaftlichen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg Tag der mündlichen Prüfung: 21.12.2010 Vorsitzender der Promotionskommision: Prof. Dr. Rainer Fink Erstberichterstatter: Prof. Dr. Lars Nitschke Zweitberichterstatter: PD Dr. Reinhard Voll Table of Contents Table of Contents Table of Contents ............................................................................................ 1 Abstract ............................................................................................................ 3 Zusammenfassung.......................................................................................... 4 1 Introduction ............................................................................................... 6 1.1 C-type lectins................................................................................................. 8 1.1.1 CLEC4L/DC-SIGN ................................................................................ 11 1.1.2 CLEC7A/Dectin-1.................................................................................. 12 1.1.3 CLEC9A/DNGR1 .................................................................................
    [Show full text]
  • IUPAC Glossary of Terms Used in Immunotoxicology (IUPAC Recommendations 2012)*
    Pure Appl. Chem., Vol. 84, No. 5, pp. 1113–1295, 2012. http://dx.doi.org/10.1351/PAC-REC-11-06-03 © 2012 IUPAC, Publication date (Web): 16 February 2012 IUPAC glossary of terms used in immunotoxicology (IUPAC Recommendations 2012)* Douglas M. Templeton1,‡, Michael Schwenk2, Reinhild Klein3, and John H. Duffus4 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; 2In den Kreuzäckern 16, Tübingen, Germany; 3Immunopathological Laboratory, Department of Internal Medicine II, Otfried-Müller-Strasse, Tübingen, Germany; 4The Edinburgh Centre for Toxicology, Edinburgh, Scotland, UK Abstract: The primary objective of this “Glossary of Terms Used in Immunotoxicology” is to give clear definitions for those who contribute to studies relevant to immunotoxicology but are not themselves immunologists. This applies especially to chemists who need to under- stand the literature of immunology without recourse to a multiplicity of other glossaries or dictionaries. The glossary includes terms related to basic and clinical immunology insofar as they are necessary for a self-contained document, and particularly terms related to diagnos- ing, measuring, and understanding effects of substances on the immune system. The glossary consists of about 1200 terms as primary alphabetical entries, and Annexes of common abbre- viations, examples of chemicals with known effects on the immune system, autoantibodies in autoimmune disease, and therapeutic agents used in autoimmune disease and cancer. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are toxicologists, pharmacologists, medical practitioners, risk assessors, and regu- latory authorities. In particular, it should facilitate the worldwide use of chemistry in relation to occupational and environmental risk assessment.
    [Show full text]
  • Biotin Homeostasis During the Cell Cycle
    Nutrition Research Reviews (2001), 14, 45–63 DOI: 10.1079/NRR200117 © The Authors 2001 Biotin homeostasis during the cell cycle Janos Zempleni1 and Donald M. Mock2* 1Department of Nutritional Science & Dietetics, University of Nebraska-Lincoln, 316 Ruth Leverton Hall, Lincoln, NE 68583, USA 2Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205, USA Peripheral blood mononuclear cells (PBMC) accumulate biotin by a Na-dependent energy-requiring transporter. This transporter might be the so-called Na-dependent multivitamin transporter, but kinetic observations suggest the existence of a second, more specific, biotin transporter. PBMC respond to proliferation by increased uptake of biotin; the increase is prob- ably mediated by an increased number of transporters on the cell surface. The inferred increase in the biotin transporter synthesis is relatively spe- cific. The increased uptake of biotin into proliferating PBMC is consistent with the hypothesis that these cells have an increased demand for biotin. Indeed, proliferating PBMC increase expression of genes encoding ␤- methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, generat- ing a quantitatively significant increased demand for biotin as a coenzyme in newly-synthesized carboxylases. Moreover, expression of the holocar- boxylase synthetase gene increases, consistent with the synthesis of new holocarboxylases. In addition, proliferating PBMC increase both the density of biotinylation of histones and the mass of biotinylated histones per cell, suggesting a potential role for biotin in transcription and replication of DNA. Biotin: Cell cycle: Peripheral blood mononuclear cells: Na-dependent multivitamin transporter The mammalian cell cycle The cell cycle is an ordered set of processes by which one cell grows and divides into two daughter cells (Murray & Hunt, 1993).
    [Show full text]
  • Unterschiedliche Immunkapazitäten Beim Rind Nach Polyklonaler
    Inaugural-Dissertation zur Erlangung der Doktorwürde der Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München Unterschiedliche Immunkapazitäten beim Rind nach polyklonaler Stimulation von Karina Lutterberg aus Leinefelde München 2017 Aus dem Veterinärwissenschaftlichen Department der Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München Lehrstuhl für Tierphysiologie Arbeit angefertigt unter Leitung von Univ.-Prof. Dr. Cornelia A. Deeg Gedruckt mit Genehmigung der Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München Dekan: Univ.-Prof. Dr. Joachim Braun Berichterstatter Univ.-Prof. Dr. Cornelia A. Deeg Korreferent/en: Univ.-Prof. Gabriela Knubben-Schweizer Tag der Promotion: 11. Februar 2017 Oma Frieda und Tante Lisa Inhaltsverzeichnis 1 EINLEITUNG..................................................................................................... 1 2 LITERATUR ...................................................................................................... 2 2.1 Bovine Neonatale Panzytopenie............................................................................... 2 2.1.1 Auftreten und Krankheitsbild der BNP ................................................................... 2 2.1.2 Ätiologie der BNP .................................................................................................. 3 2.1.3 Pathogenese der BNP .......................................................................................... 4 2.1.4 MHCI als mögliches Alloantigen ...........................................................................
    [Show full text]
  • Proquest Dissertations
    structure and expression of the fi1,4-galactosyltransferase gene in reiation to igG giycosyiation by Parvaneh AiipourJeddi Department of Immunology University College London Medical School A thesis submitted for the degree of Doctor of Philosophy University of London 1996 ProQuest Number: 10046107 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10046107 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 ABSTRACT Rheumatoid arthritis (RA) is associated with an increase in the level of serum IgG glycoforms lacking terminal galactose residues (i.e., agalactosyl IgG). The agalactosyl IgG shows altered effector functions and there is evidence that it may be pathogenic. Furthermore, levels of agalactosyl IgG have been shown to have a predictive value in RA. There is evidence that the decreased galactosylation of IgG occurs as a pre-secretory event and there are several reports relating this defect to aberrant control of the enzyme p1,4- galactosyltransferase (pi,4-GalTase). This project aimed to examine the structure and expression of the pi,4-GalTase gene in human RA and also in a murine model of arthritis, MRUMp-lpr/lpr (MRL Ipr/lpr), which shows the same defect in IgG galactosylation.
    [Show full text]
  • The Structure Biology and Application of Phytohemagglutinin (PHA) in Phytomedicine: with Special Up-To-Date References to Lectins
    Journal of Paramedical Sciences (JPS) Vol 4 (Winter 2013) Supplement ISSN 2008-4978 The structure Biology and Application of Phytohemagglutinin (PHA) in Phytomedicine: With special up-to-date references to lectins Abolfazl Movafagh1,*, Kiandokht Ghanati 2, Davar Amani 3, Seyed Mohammad Mahdavi4, Mehrdad Hashemi5, Davood Zare Abdolahi1, Hossein Darvish1, Milad Gholami1, Leyla HaghNejad1, Sara Mosammami1, Shamsi Safari1, Reyhaneh Darehgazani1, Mahnoosh Rahimi1, Nilofar Safavi Naini1, Mehdi Ghandehari Motlagh6, Mahdi Zamani7 1Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2Research Departmant of The International Branch of Shahid Beheshti University of Medical Sciences & Health Services. Tehran, Iran. 3Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4Faculty of Paramedical Sciences, Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Department of Genetics, Islamic Azad University,Tehran Medical Branch, Tehran, Iran. 6School of Dentistry, Pediatric Dentistry, Tehran University of Medical Sciences. Tehran, Iran. 7Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. *Corresponding Author: email address: [email protected] (A. Movafagh) ABSTRACT Lectins first discovered more than 100 years ago in plants, they are now known to be present throughout nature. Phytohemagglutinin (PHA), the lectin extract from the red kidney bean (Phaseolus Vulgaris), contain potent, cell agglutinating and mitogenic activities. They play a role in biological recognition phenomena involving cells and proteins towards medical applications. The present article is a brief review of the history of lectin in nature. By reviewing the web-based search for all types of peer review articles published, was initiated using ISI web of Sciences and Medline / PubMed, and other pertinent references on websites about lectins.
    [Show full text]
  • Induction of Macrophage-Mediated Tumor Lysis by the Lectin Wheat Germ Agglutinili1
    (CANCER RESEARCH 40, 3798-3803. October 1980] 0008-54 72/80/0040-0000$02.00 Induction of Macrophage-mediated Tumor Lysis by the Lectin Wheat Germ Agglutinili1 Manko Kurisu,2 3 Masatoshi Yamazaki,3 and Den'ichi Mizuno Faculty ol Pharmaceutical Sciences. University of Tokyo. Tokyo. Japan ABSTRACT syngeneic tumor system (23, 30-32). The first step in this type of cytolysis also involves interaction between the macrophages The first step in macrophage-mediated tumor lysis, effector- and the tumor cells, which is induced by antitumor antibody target contact, was studied in a C3H/He mouse-MM46 syn- (20). However, an important question remains to be answered. geneic tumor system in which antibody-dependent tumor lysis Is the contact of macrophages with tumor cells that results in by macrophages (ADMC) was observed in vitro. Various lectins cytolysis mediated only by antitumor antibody, or can any other were tested for the ability to mediate the contact between agents induce the binding of effector macrophages to target effector macrophages and target tumor cells. Several lectins, tumor cells to provoke the cytolysis? such as wheat germ agglutinin (WGA), concanavalin A, phyto- To investigate this question, we examined the ability of plant hemagglutinin, and pokeweed mitogen, were found to induce lectins to act as 'ligand" substances between effector and this contact, but only WGA also induced tumor lysis by mac target cells. The present report shows that several lectins serve rophages. Both this lectin-dependent cytolysis by macro as ligand substances and that one of these, WGA, can phages (LDMC) and the cytoadherence between macrophages induce cytolysis after mediating the binding of effector to target and tumor cells induced by WGA were inhibited by W-acetyl- cells.
    [Show full text]
  • Immune Reconstitution in Paediatric Patients with Acquired Immunodeficiency
    Department of Sanità pubblica e biologia cellulare University of Tor Vergata, Rome, Italy IMMUNE RECONSTITUTION IN PAEDIATRIC PATIENTS WITH ACQUIRED IMMUNODEFICIENCY Candidate: Simone Pensieroso Supervisor: Caterina Cancrini Opponent: Francesca Chiodi Rome 2007 ABSTRACT Background : Immune system plays a crucial role in defending organism from pathogens. However, immunological functions may be severely impaired by a number of disorders including acquired immunodeficiencies, possibly due to infections, chronic diseases, immunosuppressive drugs or surgeon therapies. In order to favour the immune reconstitution of patients with acquired immunodeficiency, various therapeutic treatments are constantly under investigation for both adults and paediatric patients. Aim of the study : To evaluate immune reconstitution in children with acquired immunodeficiency. Attention was focused on two groups of HIV-1 vertically infected children (subjected the first group to HAART from the third months of life, the second to a simplified treatment) and on a cohort a leukaemia children who underwent Umbilical Cord Blood Transplantation (UCBT). Materials and Methods : Immune restoration was principally evaluated in terms of lymphoproliferative response and T-cell receptor (TCR) repertoire. Immunological studies were complemented by routine clinical and laboratory analyses. Results : HIV-infected children showed a significant normalization of immune functions investigated, with a long-term maintaining of good clinical and immunological parameters. Also children who underwent UCBT showed a notable immune restoration. Conclusions : In HIV-infected children, an early application of antiretroviral treatment from the third month of life favours immune reconstitution and the application of a simplified regimen seems to permit the maintenance of good immunological results obtained during the previous successful HAART. In the context of transplanted children our data underline applicability and advantages of UBC compared to Bone marrow (BM) transplantations.
    [Show full text]