1. IMMUNOLOGY BASIC IMMUNOLOGY IMMUNE PATHOLOGY Árpád Lányi Attila Bácsi Éva Rajnavölgyi Department of Immunology

2. IMMUNOLOGY COURSE BASIC 26 lectures BASIC IMMUNOLOGY 4 lectures/week Weeks 1 – 7 COMPLEX PATHOLOGY 14 lectures IMMUNE PATHOLOGY 4 lectures/week Weeks 7 – 10 SEMINARS 10 Seminars 2 classes/week Weeks 1 – 10 DENTISTS 4 Seminars 2 classes/week Weeks 1 – 4 www.immunology.unideb.hu Username: student PASSWORD: download TESTS 1.BASIC + SEMINARSweek 8. I. DEMO 2013. Oct 28. (Mon.) 18:00 – 20:00 2. PATHOLOGY + PRACTICALweek 11. II. DEMO 2013. November 25. (Mon) 18:00 – 20:00

3. 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

4. IMMUNOLOGY MICROBIOLOGY EPIDEMIOLOGY CELL BIOLOGY GENETICS BIOCHEMISTRY BIOPHYSICS MOLECULAR BIOLOGY BASIC IMMUNE DEFICIENCIES HYPERSENSITIVITY REACTIONS INFECTIOUS DISEASES AUTOIMMUNITY TUMOR IMMUNOLOGY TRANSPLANTATION IMMUNOLOGY CLINICAL ALLERGOLOGY IMMUNOGENETICS IMMUNOGENOMICS ENVIRONMENTAL GENOMICS

5. Babylonian Epic of Gilgamesh (2000 B.C.) diseases, pestilence Egypt older dynastiessevere epidemics Pantheon for the god of disease HISTORY OF IMMUNOLOGY 1880 – First World Warstudy of diseases, vaccines 1920 – 1960scientific revolution, chemistry/biology Old TestamentGod’s punishment Phobeus Apollo Plague - Greek army before Troy Immunological memoryThucydides, 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” ImmunityImmunitas – exemption from service or duty Depletion theoriesNutrition/factors supporting pathogen growth become limited - even Pasteur Variolation (wild type)smallpox, ancient Chinese method practiced in Europe, too (pustular fluid or dried scabs inoculated) Lady Mary Montague, 1718….

6. Edward Jenner Edward Jenner 1749 – 1823 Immunity (protection) can be induced (cowpox - smallpox) FIRST VACCINATION

7. smallpox –Dread disease, 10% of all death –Infants, children, 20 – 50 % died –Pockmarks, blindness –Survivals – exempt from the disease –Variolationinoculation –Variolation/inoculation 1% mortality UK Cow PoxCow Pox contracted individuals – preventive effect Edward Jenner 1749 – 1823Edward Jenner 1749 – 1823 Training in St. Georges Hospital London 1772 MD,Practice in Gloucestershire, 1772 MD, St. Andrews University, Scotland Publications:Publications: –Jenner,E.(1788).Observationson the natural history of the cuckoo. Philos.Trans.R.Soc.Lond. 78, 219–212. –Jenner, E. 1798. –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. 18401840 – variolation practice in UK 1876 Koch1876 Koch Bacilli (Anthrax) 1880 Louis Pasteur1880 Louis Pasteur Viruses 2010The new small pox vaccine2010 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. VACCINATION – 1st SUCCESS OF IMMUNOLOGY

8. Louis Pasteur 1880 rabies, Louis Pasteur 1880 rabies, 1888 Pastuer Institute a a a Immunization with attenuated pathogens 1884 Ilya Mechnikoff Phagocytosis CELLULAR IMMUNOLOGY

9. Koch Laboratory Berlin 1890, Diphteria and Tetanus toxin 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. HUMORAL IMMUNE RESPONSE Humoral factors Antibodies in serum – bound to relevant pathogens

10. History & impact of immunology on human health 200 years after Jenner WHO announce smallpox eradicated 1965197019751980 Countries with more than one smallpox case per month 30 15 0 1700190018002000 Jenner Vaccination 1600 Jansen Microscope Müller Bacteria Koch’s Postulates Metchnikoff Phagocytosis Wright Antisera Kohler & Milstein Monoclonal Abs 1955 Miller T cells Zinkernagel & Doherty MHC restriction

11. YEARNAMEDISCOVERYNOBEL PRIZE 1890Emil von BehringAnti-toxins Serotherapy (diphteria) 1901 1890Robert KochTuberculosis, anthrax Cellular immunity, tuberculin reaction 1905 1883 1900 Elie Mecsnyikov Paul Ehrlich Phagocytosis, inflammation Cellular protection Side chain theory 1908 1902Charles Richet (Paul Portier) Anaphylaxis1913 1894Jules BordetComplement Antibodies/bacteriolysis 1919 1900Karl LandsteinerA/B/0 blood groups - serology1930 1940Max TheilerVaccine against yellow fever1951 Daniel BovetAnti-histamines, treatment of allergy1957 MILESTONES OF IMMUNOLOGY RESEARCH I.

12. 1944Peter Medawar Macfarlane Burnet Acquired tolerance Clonal selection theory 1960 1959Rodney Porter Gerald Edelman Antibody structure1972 Rosalyn Yalow Roger Guillemin Andrew Schally Radioimmunoassay Peptide hormon production in brain 1977 1958Baruj Benacerraf Jean Dausset, George Snell Histocompatibility antigens1980 1975George Köhler Cesar Milstein Niels Jerne Monoclonal antibody Network theory 1984 1979Susumi TonegawaGene rearrangement1987 E. Donnall Thomas Joseph Murray Transplantation immunology1990 1974Rolf Zinkernagel, Peter Doherty MHC restriction1996 MILE STONES OF IMMUNOLOGY RESEARCH II.

13. THEMATICS ELEMENTS, STRUCTURE & FUNCTION OF THE IMMUNE SYSTEM –Cellular interactions – direct & indirect –Organs, tissues, cell types –Two arms of the immune system Characteristics of innate immunity Characteristics of acquired immunity 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 Migration, adhesion Cytokine & chemokine receptors and ligands Cellular killing mehanisms REGULATION OF IMMUNE RESPONSES –Tolerance and immunity –Immunologaical memory

14. MICROBES 90% PATHOGENPATHOGEN COMMENSALCOMMENSAL Individuals 7 BILLION GENETIC POLYMORPHISM MHC GENES Recognition of variablity in a context of self/nonself safe /dangerous DIVERSITY RAPID REPRODUCTION ADAPTATION Geographic borders Population density Biodiversity Life style BIOMASSENVIRONMENTMANKIND v v v v v v v v v v v v vvv v v v v v v v v v EPIDEMIC PANDEMIC WE LIVE IN A MICROBIAL RICH ENVIRONMENT

15. Bacteria Víruses Multicellular parazites (worms) Unicellular parazites Rapid genetic changes Selection driven evolution AdaptationSelection Virus 3 hours 18 - 30 years ENVIRONMENT - Microbial and other effects Cells of human body: 90% microbes, 10% human 10 12 (1.5kg) bacteria in the gut Human population: 7x10 9 (7 billion) Biomass: 90% microbes Animal mass < 5 – 25x microbes

16. Numerous commensal microorganisms inhabit healthy human bodies Pathogens are infectious organisms that cause disease The skin and mucosal surfaces form barriers against infection Chapter 1 © Garland Science 2009 Elements of the Immune System and their Roles in Defense