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IMMUNOLOGY BASIC IMMUNOLOGY IMMUNE PATHOLOGY Árpád Lányi Attila Bácsi Éva Rajnavölgyi Department of Immunology IMMUNOLOGY COURSE SEMINARS BASIC 26 lectures BASIC IMMUNOLOGY 4 lectures/week Weeks 1 – 7 10 Seminars 2 classes/week Weeks 1 – 10 COMPLEX PATHOLOGY DENTISTS 14 lectures IMMUNE PATHOLOGY 4 lectures/week Weeks 7 – 10 4 Seminars 2 classes/week Weeks 1 – 4 www.immunology.unideb.hu Username: student PASSWORD: download TESTS 1. BASIC + SEMINARS week 8. I. DEMO 2013. Oct 28. (Mon.) 18:00 – 20:00 2. PATHOLOGY + PRACTICAL week 11. II. DEMO 2013. November 25. (Mon) 18:00 – 20:00 BOOKS Peter Parham: The immune system (Garland Science) 3rd Edition 2009 Abul K Abbas, Andrew H. Lichtman and Shiv. Pillai: Basic Immunology Fouth Ed. 2014 Elsevier, Sanders Janeway C.A. Jr., Travers P., Walport M., Shlomchik M.: Immunbiology (Garland Publishing) 5th Edition 2001 Rosen F., Geha R.: Case Studies in Immunology (Garland Publishing) 4th Edition 2004 IMMUNOLOGY MICROBIOLOGY EPIDEMIOLOGY IMMUNOLOGY BASIC CLINICAL ALLERGOLOGY CELL BIOLOGY GENETICS BIOCHEMISTRY BIOPHYSICS IMMUNOGENETICS IMMUNOGENOMICS MOLECULAR BIOLOGY ENVIRONMENTAL GENOMICS IMMUNE DEFICIENCIES HYPERSENSITIVITY REACTIONS INFECTIOUS DISEASES AUTOIMMUNITY TUMOR IMMUNOLOGY TRANSPLANTATION IMMUNOLOGY HISTORY OF IMMUNOLOGY Babylonian Epic of Gilgamesh (2000 B.C.) diseases, pestilence Egypt older dynasties severe epidemics Pantheon for the god of disease Old Testament Phobeus Apollo God’s punishment Plague - Greek army before Troy Immunological memory Thucydides, historian, Athen 430 B.C. pestilence epidemics „yet it was with those who recovered from the disease that the sick and the dying found most compassion……. No fear for themselves; as no man was never attacked twice-never at least fatally” Immunity Depletion theories Variolation (wild type) 1880 – First World War 1920 – 1960 Immunitas – exemption from service or duty Nutrition/factors supporting pathogen growth become limited - even Pasteur smallpox, ancient Chinese method practiced in Europe, too (pustular fluid or dried scabs inoculated) Lady Mary Montague, 1718…. study of diseases, vaccines scientific revolution, chemistry/biology FIRST VACCINATION Edward Jenner 1749 – 1823 Immunity (protection) can be induced (cowpox - smallpox) VACCINATION – 1st SUCCESS OF IMMUNOLOGY • smallpox – – – – – • • • • • Cow Pox contracted individuals – preventive effect Edward Jenner 1749 – 1823 Training in St. Georges Hospital London Practice in Gloucestershire, 1772 MD, St. Andrews University, Scotland Publications: – – – – • • • • Dread disease, 10% of all death Infants, children, 20 – 50 % died Pockmarks, blindness Survivals – exempt from the disease Variolation/inoculation 1% mortality UK Jenner,E.(1788).Observationson the natural history of the cuckoo. Philos.Trans.R.Soc.Lond. 78, 219–212. Jenner, E. 1798. An Inquiry into the Causes and Effects of Variolae Vaccinae,a Disease Discovered in Some Western Counties of England. London: Sampson Low. Jenner,E.(1799). Further Observations on the Variolae Vaccinae. London: Sampson Low. Jenner,E.(1800). A Continuation of Facts and Observations Relative to the Variolae Vaccinae or Cow Pox. London: Sampson Low. 1840 – variolation practice in UK 1876 Koch Bacilli (Anthrax) 1880 Louis Pasteur Viruses 2010 Nalca A and Zumbrun E: ACAM 2000: The new small pox vaccine for US strategic national stock- plie. Drug Des. Devel. Ther. 4, 71–79. ACAM2000 (Acambis, Inc.) cell culture based…. over 200 million doses of ACAM2000 have been produced for the US Strategic National Stockpile. Louis Pasteur 1880 rabies, 1888 Pastuer Institute 1884 Ilya Mechnikoff Phagocytosis Immunization with attenuated pathogens CELLULAR IMMUNOLOGY Koch Laboratory Berlin 1890, Diphteria and Tetanus toxin Antibodies in serum – bound to relevant pathogens Humoral factors HUMORAL IMMUNE RESPONSE Emil Behring Shimbasaru Kitasato 1. Many disease occurs only once (natural protection) 2. Some diseases can be prevented by vaccination 3. The blood contains anti-bacterial activity (anti-toxins, serum therapy) 4. worked on antitoxins for tetanus diphtheria and anthrax. History & impact of immunology on human health Koch’s Kohler & Milstein Postulates Monoclonal Abs Metchnikoff Phagocytosis Müller Jenner Wright Miller Bacteria Vaccination Antisera T cells Jansen Microscope 1600 1700 1800 1900 2000 1955 Zinkernagel & Doherty MHC restriction 200 years WHO announce after Jenner smallpox eradicated 30 Countries with more than one smallpox case 15 per month 0 1965 1970 1975 1980 MILESTONES OF IMMUNOLOGY RESEARCH I. YEAR NAME DISCOVERY NOBEL PRIZE 1890 Emil von Behring Anti-toxins Serotherapy (diphteria) 1901 1890 Robert Koch Tuberculosis, anthrax Cellular immunity, tuberculin reaction 1905 1883 Elie Mecsnyikov 1908 1900 Paul Ehrlich Phagocytosis, inflammation Cellular protection Side chain theory 1902 Charles Richet (Paul Portier) Anaphylaxis 1913 1894 Jules Bordet Complement Antibodies/bacteriolysis 1919 1900 Karl Landsteiner A/B/0 blood groups - serology 1930 1940 Max Theiler Vaccine against yellow fever 1951 Daniel Bovet Anti-histamines, treatment of allergy 1957 MILE STONES OF IMMUNOLOGY RESEARCH II. 1944 Peter Medawar Macfarlane Burnet Acquired tolerance Clonal selection theory 1960 1959 Rodney Porter Gerald Edelman Antibody structure 1972 Rosalyn Yalow Roger Guillemin Andrew Schally Radioimmunoassay Peptide hormon production in brain 1977 1958 Baruj Benacerraf Jean Dausset, George Snell Histocompatibility antigens 1980 1975 George Köhler Cesar Milstein Niels Jerne Monoclonal antibody 1984 Susumi Tonegawa Gene rearrangement 1987 E. Donnall Thomas Joseph Murray Transplantation immunology 1990 Rolf Zinkernagel, Peter Doherty MHC restriction 1996 1979 1974 Network theory THEMATICS • ELEMENTS, STRUCTURE & FUNCTION OF THE IMMUNE SYSTEM – – – Cellular interactions – direct & indirect Organs, tissues, cell types Two arms of the immune system • • • RECOGNITION BY THE IMMUNE SYSTEM – SIGNAL TRANSDUCTION – – – Pattern recognition receptors Antigen recognition by B-lymphocytes Antigen recognition by T- lymphocytes • • • Role of MHC proteins in antigen presentation Antigen processing and presentation for T-lymphocytes CELL ACTIVATION, DIFFERENTIATION, COMMUNICATION – – Receptors – Co-receptors – Adhesion molecules Effector mechanisms • • • • Characteristics of innate immunity Characteristics of acquired immunity Migration, adhesion Cytokine & chemokine receptors and ligands Cellular killing mehanisms REGULATION OF IMMUNE RESPONSES – – Tolerance and immunity Immunologaical memory WE LIVE IN A MICROBIAL RICH ENVIRONMENT ENVIRONMENT BIOMASS C O M M E N S A L P A T H O Individuals G E N MICROBES 90% DIVERSITY RAPID REPRODUCTION ADAPTATION MANKIND v v EPIDEMIC v v v v v Geographic borders Population density Biodiversity Life style v v PANDEMIC v v v v v v v v v v v v v v v 7 BILLION GENETIC POLYMORPHISM MHC GENES Recognition of variablity in a context of self/nonself safe /dangerous ENVIRONMENT - Microbial and other effects Cells of human body: 90% microbes, 10% human 1012 (1.5kg) bacteria in the gut Human population: 7x109 (7 billion) Biomass: 90% microbes Animal mass < 5 – 25x microbes Bacteria Virus Víruses Unicellular parazites 3 hours 3 hours 18 - 30 years Multicellular parazites (worms) Rapid genetic changes Selection driven evolution Adaptation Selection Chapter 1 Elements of the Immune System and their Roles in Defense • Numerous commensal microorganisms inhabit healthy human bodies • Pathogens are infectious organisms that cause disease • The skin and mucosal surfaces form barriers against infection © Garland Science 2009