IMMUNOLOGY
BASIC IMMUNOLOGY
IMMUNE PATHOLOGY
Árpád Lányi
Attila Bácsi
Éva Rajnavölgyi
Department of ImmunologyDepartment of Immunology
IMMUNOLOGY COURSE
BASIC
26 lectures BASIC IMMUNOLOGY 4 lectures/weekWeeks 1 – 7
COMPLEX PATHOLOGY
14 lectures IMMUNE PATHOLOGY4 lectures/weekWeeks 7 – 10
SEMINARS
10 Seminars2 classes/weekWeeks 1 – 10
DENTISTS4 Seminars2 classes/weekWeeks 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
IMMUNOLOGY
MICROBIOLOGY
EPIDEMIOLOGY
CELL BIOLOGYGENETICSBIOCHEMISTRYBIOPHYSICSMOLECULAR BIOLOGY
BASIC
IMMUNE DEFICIENCIES
HYPERSENSITIVITY REACTIONS
INFECTIOUS DISEASES
AUTOIMMUNITY
TUMOR IMMUNOLOGY
TRANSPLANTATION IMMUNOLOGY
CLINICAL
ALLERGOLOGY
IMMUNOGENETICSIMMUNOGENOMICS
ENVIRONMENTAL GENOMICS
Babylonian Epic of Gilgamesh (2000 B.C.) diseases, pestilence
Egypt older dynasties severe epidemics
Pantheon for the god of disease
HISTORY OF IMMUNOLOGY
1880 – First World War study of diseases, vaccines
1920 – 1960 scientific revolution, chemistry/biology
Old Testament God’s punishmentPhobeus Apollo Plague - Greek army before Troy
Immunological memory Thucydides, historian, Athen430 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 wasnever attacked twice-never at least fatally”
Immunity Immunitas – exemption from service or dutyDepletion theories Nutrition/factors supporting pathogen growth become
limited - even PasteurVariolation (wild type) smallpox, ancient Chinese method
practiced in Europe, too (pustular fluid or dried scabsinoculated) Lady Mary Montague, 1718….
Edward Edward Jenner Jenner 1749 – 1823
Immunity (protection) can be Immunity (protection) can be iinduced (cowpoxnduced (cowpox - smallpox)- smallpox)
FIRST VACCINATIONFIRST VACCINATION
• smallpox – Dread disease, 10% of all death– Infants, children, 20 – 50 % died– Pockmarks, blindness– Survivals – exempt from the disease– VariolationVariolation/inoculationinoculation 1% mortality UK
• Cow PoxCow Pox contracted individuals – preventive effect • Edward Jenner 1749 – 1823Edward Jenner 1749 – 1823• Training in St. Georges Hospital London • Practice in Gloucestershire, 1772 MD, 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• 20102010 Nalca A and Zumbrun E: ACAM 2000: The new small pox vaccineThe 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 IMMUNOLOGYVACCINATION – 1st SUCCESS OF IMMUNOLOGY
Louis PasteuLouis Pasteurr11880 rabies, 880 rabies, 1888 Pastuer Institute
Immunization with attenuated pathogens
1884 Ilya Mechnikoff
Phagocytosis
CELLULAR IMMUNOLOGY
KochKoch Laboratory Laboratory Berlin 1890Berlin 1890, , Diphteria and Tetanus toxinDiphteria and Tetanus toxin
Emil BehringEmil Behring ShimbasaruShimbasaru KitasatoKitasato1. 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
History & impact of immunology on human health
200 yearsafter Jenner
WHO announcesmallpox eradicated
1965 1970 1975 1980
Countries withmore than onesmallpox case
per month
30
15
0
1700 19001800 2000
Jenner Vaccination
1600
JansenMicroscope
Müller Bacteria
Koch’sPostulatesMetchnikoff
Phagocytosis
WrightAntisera
Kohler & MilsteinMonoclonal Abs
1955
MillerT cells
Zinkernagel& Doherty
MHC restriction
YEAR NAME DISCOVERY NOBEL PRIZE
1890 Emil von Behring Anti-toxinsSerotherapy (diphteria)
1901
1890 Robert Koch Tuberculosis, anthraxCellular immunity, tuberculin reaction
1905
1883
1900
Elie Mecsnyikov
Paul Ehrlich
Phagocytosis, inflammationCellular protectionSide chain theory
1908
1902 Charles Richet(Paul Portier)
Anaphylaxis 1913
1894 Jules Bordet ComplementAntibodies/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
MILESTONES OF IMMUNOLOGY RESEARCH I.
1944 Peter MedawarMacfarlane Burnet
Acquired toleranceClonal selection theory
1960
1959 Rodney PorterGerald Edelman
Antibody structure 1972
Rosalyn YalowRoger GuilleminAndrew Schally
RadioimmunoassayPeptide hormon production in brain
1977
1958 Baruj Benacerraf Jean Dausset, George Snell
Histocompatibility antigens 1980
1975 George KöhlerCesar MilsteinNiels Jerne
Monoclonal antibody
Network theory
1984
1979 Susumi Tonegawa Gene rearrangement 1987
E. Donnall ThomasJoseph Murray
Transplantation immunology 1990
1974 Rolf Zinkernagel, Peter Doherty
MHC restriction 1996
MILE STONES OF IMMUNOLOGY RESEARCH II.
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
MICROBES90%
PATHOGEN
COMMENSAL
Individuals
7 BILLION
GENETIC POLYMORPHISMMHC GENES
Recognition of variablity in a context of self/nonself
safe /dangerous
DIVERSITYRAPID REPRODUCTION
ADAPTATION
Geographic bordersPopulation density
BiodiversityLife style
BIOMASSBIOMASS ENVIRONMENTENVIRONMENT MANKINDMANKIND
v
vv
vv
v
vv
v
v
v
v
v v v
v
vv
v
vv
v
vv
EPIDEMIC
PANDEMIC
WE LIVE IN A MICROBIAL RICH ENVIRONMENTWE LIVE IN A MICROBIAL RICH ENVIRONMENT
BaBacteriacteria
VVírusesíruses
Multicellular parazites (wMulticellular parazites (woorms)rms)
Unicellular paraziUnicellular parazitteses
Rapid genetic changesRapid genetic changesSelection driven evolutionSelection driven evolution
AdaptationAdaptationSelection Selection
VViirusrus
3 3 hourshours
3 3 hourshours18 - 30 years
ENVIRONMENT - Microbial and other effectsENVIRONMENT - Microbial and other effectsCells of human body: 90% microbes, 10% human
1012 (1.5kg) bacteria in the gut Human population: 7x109 (7 billion)
Biomass: 90% microbesAnimal mass < 5 – 25x microbes
• 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