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

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