Part 1. General Microbiology & Medical Immunology
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I.I. Generalov MEDICAL MICROBIOLOGY, VIROLOGY & IMMUNOLOGY Part 1. General Microbiology & Medical Immunology Lecture Course for Students of Medical Universities VITEBSK STATE MEDICAL UNIVERSITY 2016 УДК [579+616.31]=111(07) ББК 52.64 я73+56.6 я73 Г 34 Printed according to the decision of Educational&Methodological Concociation on Medical Education (July 1, 2016) Reviewed by: D.V.Tapalsky, MD, PhD, Head of Microbiology, Virology and Immunology Dpt, Gomel State Medical University Microbiology, Virology and Immunology Dpt, Belarussian State Medical University, Minsk Generalov I.I. Г 34 Medical Microbiology, Virology and Immunology. Part 1. General Microbiology & Medical Immunology – Lecture Course for students of medical universities / I.I. Generalov. – Vitebsk, - VSMU. - 2016. - 282 p. ISBN 978-985-466-743-0 The Lecture Course on Medical Microbiology, Virology and Immunology accumulates a broad scope of data covering the most essential areas of medical microbiology. The textbook is composed according to the educational standard, plan and program, approved by Ministry of Education and Ministry of Health Care of Republic of Belarus. This edition encompasses all basic sections of the subject – General Microbiology, Medical Immunology, Medical Bacteriology and Virology. Part 1 of the Lecture Course comprises General Microbiology and Medical Immunology sections. This book is directed for students of General Medicine faculties and Dentistry faculties of higher educational establishments. УДК [579+616.31]=111(07) ББК 52.64 я73+56.6 я73 © Generalov I.I., 2016 © VSMU Press, 2016 ISBN 978-985-466-743-0 2 CONTENTS Pages Abbreviation list 5 Section 1. GENERAL MICROBIOLOGY` 8 Chapter 1. The subject and basic fields of modern microbiology. A brief historical overview on microbiology 9 Chapter 2. Principles of microbial classification. Morphology and ultrastructure of bacteria. Basic methods for examination of microbial morphology 18 Chapter 3. Morphology and ultrastructure of spirochetes, rickettsiae, chlamydiae, and mycoplasmas. Morphology of actinomycetes and fungi 43 Chapter 4. Nutrition of bacteria. Biological oxidation in bacteria. Growth and reproduction of bacteria 54 Chapter 5. Microbial genetics. Methods of molecular genetic analysis 80 Chapter 6. Normal microflora of human body. 109 Microflora of oral cavity (for students of Dentistry Faculty) 118 Chapter 7. Microorganisms and the environment. Basic principles of sanitary microbiology 129 Chapter 8. Antimicrobial measures: sterilization, antisepsis, disinfection, and asepsis 141 Chapter 9. Chemotherapy. Antibiotics 147 Chapter 10. Infectious process. Characteristics of infectious diseases. Pathogenicity and virulence. Bacterial virulence factors 160 Section 2. MEDICAL IMMUNOLOGY 174 Chapter 11. Immunology and immunity – basic definitions. Structure of immune system. Differentiation of T- and B-lymphocyte subsets, their functions 175 Chapter 12. Basic mechanisms of innate immune response. Pathogen- binding receptors. Phagocytes and phagocytosis 194 Chapter 13. Antigens: structure and properties. Major infectious and non-infectious antigens. HLA system 205 Chapter 14. Immunoglobulins and antibodies, their structure and functions. Complement system. Pathways of complement activation 215 Chapter 15. Primary and secondary immune response. Dynamics of immune response 227 3 Chapter 16. Non-immune and immune defensive mechanisms in oral cavity (for students of Dentistry faculty) 235 Chapter 17. Immunodiagnostics. Evaluation of immune status. Serological reactions and their practical applications 243 Chapter 18. Immunopathology: types of hypersensitivity. Allergy and autoimmune diseases. Primary and secondary imunodeficiencies 264 Chapter 19. Immunoprophylaxis and immunotherapy. Vaccines, immune sera and antibodies 276 4 ABBREVIATION LIST Ab – antibody ADCC – antibody-dependent cell-mediated cytotoxicity AFM – atomic force microscopy Ag – antigen APC – antigen-presenting cell ATP – adenosine triphosphate BALT – bronchial-associated lymphoid tissue BCR – B cell receptor CALT – conjunctival-associated lymphoid tissue cAMP – 3',5'-cyclic AMP CAP – cyclic AMP-binding protein Cas proteins – CRISPR-associated proteins CD – clusters of differentiation CDRs – complementarity-determining regions CFU – colony-forming units CLSI – Clinical and Laboratory Standards Institute CRISPR – clustered regularly interspaced short palindromic repeat CRP – C-reactive protein DAF – decay-accelerating factor DAMPs – damage-associated molecular patterns DAP – diaminopimelic acid DC – dendritic cell Dcl – dosis certa letalis ddNTP – dideoxy-nucleotides DLM – dosis letalis minima DNA – deoxyribonucleic acid EGF – endothelial growth factor ELISA – enzyme-linked immunosorbent assay EPS – extracellular polymeric substance EUCAST – European Committee on Antimicrobial Susceptibility Testing FACS – fluorescence-activated cell sorter FAE cells – follicule-associated epithelial cells FITC – fluorescein isothiocyanate FRET – fluorescence resonance energy transfer GALT – gut-associated lymphoid tissue G-CSF – granulocyte-colony stimulating factor GM-CSF – granulocyte-macrophage-colony stimulating factor GTP – guanosine triphosphate HA – hemagglutinin Hfr – high frequency of recombination HIV – human immunodeficiency virus 5 HLA – human leukocyte antigen IFN – interferon IL – interleukin ICSP – International Committee on Systematics of Prokaryotes ICTV – International Committee on Taxonomy of Viruses IU – International Unit IUPAC – International Union of Pure and Applied Chemistry LATS-factor – long acting thyroid stimulator LPS – lipopolysaccharide LSCM – laser scanning confocal microscopy M cells – microfold cells mAbs – monoclonal antibodies MALDI-TOF analysis – matrix-assisted laser desorption ionization – time-of-flight detection analysis MALT – mucosal-associated lymphoid tissue MAС – membrane attack complex MBC – minimum bactericidal concentration MBL – mannose-binding lectin MHC – major histocompatibility complex MIC – minimum inhibitory concentration MPA – meat-peptone agar MPB – meat-peptone broth MPS – mononuclear phagocyte system mRNA – messenger RNA MRSA – methicillin resistant Staphylococcus aureus NA – neuraminidase NALT – nasal-associated lymphoid tissue NBT-test – nitroblue tetrazolium reduction test NETs – neutrophil extracellular traps NGS – next-generation sequencing NK cell – natural killer cell PABA – p-aminobenzoic acid PAF – platelet-activating factor PAGE – polyacrylamide gel electrophoresis PAMP – pathogen-associated molecular patterns PBP – penicillin-binding protein PCR – polymerase chain reaction PDGF – platelet-derived growth factor PTFE – polytetrafluoroethylene R genes – resistance genes RA – rheumathoid arthritis Rag – recombination-activating genes Rh – rhesus factor 6 RIA – radioimmunoassay RNA – ribonucleic acid ROS – reactive oxygen species RTF – resistance transfer factor SARS – severe acquired respiratory syndrome SDS – sodium dodecyle sulfate SEM – scanning electron microscopy SLE – systemic lupus erythematosus SMRT sequencing – single molecule real time sequencing SRBC – sheep red blood cell SRID – single radial immunodiffusion SS – secretion system STED-microscopy – stimulated emission-depletion fluorescent microscopy Tc – T cytotoxic cell TCA – tricarboxylic acid TCR – T cell receptor ТЕМ – transmission electron microscopy TFH – follicular T helper cell TGF – transforming growth factor Th – T helper cell TLR – Toll-like receptor TNF – tumor necrosis factor TSST – toxic shock syndrome toxin TST – tuberculin skin test UV – ultraviolet VRE – vancomycin-resistant enterococci 7 GENERAL MICROBIOLOGY 8 Chapter 1 THE SUBJECT AND BASIC FIELDS OF MODERN MICROBIOLOGY. A BRIEF HISTORICAL OVERVIEW ON MICROBIOLOGY The Subject and Main Tasks of Microbiology The microbiology has grown up into independent scientific discipline from the more aged science, biology. Any branch of knowledge is regarded as a science, if it operates with the own subject of study and has its intrinsic methods of research. The subject of microbiology is the special world of living beings invisible by naked eye which sizes are within the range from 1-10 nm up to 0.1-1 mm. Microorganisms comprise several diverse groups of agents – bacteria, viruses, protozoans, fungi, and prions (the latter are known as “proteinaceus infectious particles” or infectious proteins). The title of the science “microbiology” originates from combination of Greek words – “micros” – minute, “bios” – the life, “logos” – the science. Thus, microbiology is the science that studies the life and development of smallest living creatures – microorganisms – together with their complex environmental relationships. Taking into account the tremendous role the microorganisms play in nature, the problems of microbiology are rather diverse. Microbiology steadily differentiates into various scientific parts and disciplines. Modern microbiology includes general microbiology (investigates common principles of structural organization and general functions of microorganisms), special microbiology (performs the detailed study of certain microbial agents and groups); industrial microbiology that is the major part of modern biotechnology; agricultural microbiology; space microbiology; sanitary microbiology; veterinary microbiology; and medical microbiology. The subject of medical microbiology encompasses pathogenic microorganisms that cause the diseases in humans and those non- pathogenic microorganisms – inhabitants of living beings or external environment – that can