1. INTRODUCTION TO IMMUNOLOGY
Immunology - scientific subject
Immune system, immunity
Immune mechanisms
Immunity – innate, acquired
Immune response
- characterisation
- cardinal features
- phases
Nobel prize winners in immunology

2. IMMUNOLOGY
scientific subject - studies immune system (cellular and humoral
reactions after MAO comes to contact to foreign
body)
General - studies cellular and molecular fundaments of immune
system
Clinical - uses and interprets General immunology in clinical
practice (diagnostics, therapy, prevention)

3. IMMUNOLOGY   Immune system Immunity    Immune response 
Nonspecific immune mechanisms  Innate
Specific immune mechanisms  Acquired

4. IMMUNE MECHANISMS Nonspecific IM A) Basic barriers of an individual
- anatomical, - physiological, - biochemical, - biological, - genetic
B) Amplification mechanisms
- other slide (do you know something about ?)
Specific IM
A) T Ly
B) B Ly
C) Immunoglobulines
D) Lymphocyte cytokines

5. A) Basic barriers of an individual
IMMUNE MECHANISMS
Nonspecific IM
A) Basic barriers of an individual
ANATOMICAL
- intact barriers that prevent the entry of many microbes
a. Skin - consists of the epidermis and the dermis
b. Mucous membranes
- line body cavities that open to the exterior - RT, GIT and GUT
- composed of - an epithelial layer, which secretes mucous, and
- a connective tissue layer.
c. Bony encasements - the skull and the thoracic cage
- protect vital organs from injury and entry of
microbes.

6. A) Basic barriers of an individual
IMMUNE MECHANISMS
Nonspecific IM
A) Basic barriers of an individual
PHYSIOLOGICAL
Mucous and cilia
Mucous traps MIO and contains various antimicrobial agents.
Cilia on the surface of the epithelial cells propels mucous and trapped microbes upwards towards the throat where it is swallowed.
b. Cough and sneeze reflex - removes mucous and trapped microbes.
c. Vomiting and diarrhea - remove pathogens and toxins in the gastrointestinal tract.
d. Physical washing action of body fluids - Fluids such as urine, tears, saliva, perspiration, and blood from injured blood vessels also flush microbes from the body.

7. A) Basic barriers of an individual
IMMUNE MECHANISMS
Nonspecific IM
A) Basic barriers of an individual
BIOCHEMICAL
many antigen-nonspecific antimicrobial chemicals produced by the host that play roles
in innate body defense. Examples include the following:
Hydrochloric acid and enzymes in gastric secretions destroy
microbes which are swallowed.
2. Lysozyme - in tears, mucous, saliva, plasma tissue fluid, etc.,
- breaks down peptidoglycan in bacteria causing osmotic
lysis.
3. Human beta-defensin-2 - in blood plasma, put holes in the cytoplasmic membrane of a variety of bacteria.
4. Lactic and fatty acids in perspiration and sebaceous secretions inhibit microbes on the skin.

8. A) Basic barriers of an individual
IMMUNE MECHANISMS
Nonspecific IM
A) Basic barriers of an individual
BIOLOGICAL
- bacterial antagonism by normal flora
Approximately 100 trillion MIO reside in or on the human body. These normal body flora keep potentially harmful opportunistic pathogens in check and also inhibit the colonization of pathogens by:
1. producing metabolic products (fatty acids, bacteriocins, etc.) that
inhibit the growth of many pathogens;
2. Prevention of pathogen colonisation - adhering to target host cells thus covering them and preventing pathogens from colonizing;
3. Depleting nutrients essential for the growth of pathogens; and
4. Nonspecifically stimulating the immune system.

9. B) Amplification mechanisms
IMMUNE MECHANISMS
Nonspecific IM
B) Amplification mechanisms
- complement,
- phagocytosis,
- NK cells,
- acute phase inflammatory proteins (see next picture)
- macrophage cytokines
- interferons
- interleukins 1 – 22
- chemokines
- Colony Stimulating Factors
- other cytokines - TumorNecrosisFactor alpha and TNFbeta
- Transforming Growth Factor-beta
- particularly important in mediating inflammation and cytotoxic
reactions

10. B) Amplification mechanisms
IMMUNE MECHANISMS
Nonspecific IM
B) Amplification mechanisms
Acute phase proteins(APPs) in man
Positive - concentration during inflammation increases in serum
Major Acute Phase Proteins Serum amyloid A, C-reactive proteín
Complement C2, C3, C4, C5, C9, B, C1-INH, C4bp
Hemocoagulation Fibrinogen, von Willebrand factor
Protease inhibitors alpha1-antitrypsin, alpha1-antichymotrypsin, alpha1-
antiplazmin, heparin factor II
Metal binding proteins Haptoglobin, hemopexin, ceruloplazmin
Other APPs alpha1-acid glycoprotein, hem oxygenase, mannose-binding
protein (MBP)
Negative – its concentration during inflammation decreases in serum
Albumin, pre-alburnin, transferín, apolipoprotein-Al, apoAII,
alpha2-HS-glycoprotein

11. IMMUNITY Innate Acquired (nospecific) (specific)
___________________________  
Active Passive    
Natural Arteficial Natural Arteficial
(postinfectious) (postvaccinated) (Ab transfer (administration
mother-child) of Ab)

12. Innate immunity
refers to antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any antigen. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

13. Innate immunity
does not recognize every possible antigen.
designed to recognize a few highly conserved structures present in many different microorganisms.
The structures recognized are called pathogen-associated molecular patterns (PAMP) and include
- LPS (lipopolysaccharide) - gram-negative cell wall,
- peptidoglycan, lipotechoic acids - gram-positive cell wall,
- mannose - common in microbial glycolipids and glycoproteins, rare in humans,
- bacterial DNA, double-stranded RNA - viruses
- N-formylmethionine found in bacterial proteins,
- glucans - fungal cell walls.
PAMPs are recognized by
- pattern-recognition receptors present on most body defense cells and so there is an immediate response against the invading microorganism (
- soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways.
Innate immune system is thought to recognize approximately 103 molecular patterns.

14. Innate immunity 1. TLRs found on cell surfaces:
a. TLR-1/TLR-2 pairs bind uniquely bacterial lipopeptides and glycosylphosphatidylinositol (GPI)-anchored proteins in parasites; b. TLR-2/TL6 pairs bind lipoteichoic acid from gram-positive cell walls and zymosan from fungi; c. TLR-2 plays a role in binding peptidoglycan fragments (glycopeptides); d. TLR-4/TLR-4 pairs bind lipopolysaccharide from gram-negative cell walls; e. TLR-5* binds bacterial flagellin;
2. TLRs found in the membranes of the endosomes used to degrade pathogens:
a. TLR-3* binds double-stranded viral RNA; b. TLR-7* binds uracil-rich single-stranded viral RNA such as in HIV; c. TLR-8* binds single-stranded viral RNA; d. TLR-9* binds unmethylated cytosine-guanine dinucleotide sequences (CpG DNA) found in bacterial and viral genomes.
The binding of a MIO molecule to its TLR transmits a signal to the cell's nucleus inducing
the expression of genes coding for the synthesis of i.c. regulatory molecules - cytokines.

15. IMMUNE RESPONSE
1. CHARACTERISATION
2. CARDINAL FEATURES
3. PHASES

16. IMUNNE RESPONSE
1. CHARACTERISATION
Collective and coordinated activity of immune mechanisms against
particles recognized as non-self

17. IMUNNE RESPONSE
2. CARDINAL FEATURES
A. SPECIFICITY
B. DIVERSITY
C. MEMORY
D. SELF-REGULATION
E. DISCRIMINATION OF „SELF“ FROM „NON-SELF“

18. A. SPECIFICITY IMUNNE RESPONSE 2. CARDINAL FEATURES
I.R. - specific for distinct Ag
portions of Ag (Ag determinants – epitopes) are specifically
recognized by Ly

20. B. DIVERSITY IMUNNE RESPONSE 2. CARDINAL FEATURES
I.S. discriminates  epitopes
= lymphocyte repertoire

21. C. MEMORY IMUNNE RESPONSE 2. CARDINAL FEATURES
- second and subsequent contact I.S. to Ag (called secondary
immune response) is usually more rapid, larger from the first-
primary interaction of I.S. to same Ag (primary immune
response)
= immunologic memory

22. D. SELF-REGULATION IMUNNE RESPONSE 2. CARDINAL FEATURES
Normal I.R. wane with time
Reasons: - elimination of Ag
- I.R. stimulates mechanisms, whose principal
function is feedback regulation of the I.R.

23. E. DISCRIMINATION OF SELF FROM NON-SELF
IMUNNE RESPONSE
2. CARDINAL FEATURES
E. DISCRIMINATION OF SELF
FROM NON-SELF
Ly recognize and respond to any non-self Ag
Ly do not recognize and respond to self Ag
= TOLERANCE
Ly „learn“ tolerate „self“ in the process of
positive and negative selection

24. IMUNNE RESPONSE 3. PHASES a. Cognitive b. Activation c. Efector
a. Cognitive phase of immune response
- Ag binding to specific Ly receptor
     - T Ly recognize short peptide sequences of
protein Ag
     -  B Ly recognize Ag - protein
- polysaccharide
- lipid

25. IMUNNE RESPONSE 3. PHASES b. Activation phase of immune response
During activation two major changes occur in Ly :
  PROLIFERATION after interaction to Ag Ly proliferate → clone
expansion
  2. DIFERENTIATION
B Ly → plasma cells
T Ly → TH → TH1 – activation of Ma
→ TH2 – activation of TCLy

26. IMUNNE RESPONSE 3. PHASE c. Efector phase of immune response
- Ly (specifically activated by Ag)
- PMNL, Ma
- other defense mechanims
(e.g. complement)
Ab production (neutralisation of toxins, support of phagocytosis)
cytokine production → ↑ Ma function, elimination of inflammation
Removal of target cells infected by viruses

27. NOBEL PRIZE WINNERS IN IMMUNOLOGY
Emil von Boehring
Robert Koch
1890 – passive immunisation
1890 – delayed hypersensitivity

28. IljaMečnikov 1845-1916 1898 – humoral immunity 1908
Paul Ehrlich
IljaMečnikov
                                           
1898 – humoral immunity 1908
1883 – phagocytosis 1908

29. Charles Robert Richet 1850 - 1935 Jules Bordet 1902 - anafylaxis 1913
                               
Jules Bordet
                                            
anafylaxis
1894 – complement system 1919

30. Frank Macfarlane Burnet 1899- 1985 Peter Brian Medawar 1915 - 1987
                               
Peter Brian Medawar
1953 – Discovery of immunologic tolerance 1960

31. Rodney Robert Porter
Gerald Maurice Edelman
1929-
1959 – structure of immunoglobulines 1972

32. regulating immune reactions 1980
George D. Snell
Baruj Benacerraf
1920 -
Jean Dausset
1916 -
                               
– Discovery of genetically encoded structures on cell surface
regulating immune reactions

33. 1974 – Theory of development and control of immune system
                               
                               
                               
Niels K.Jerne
Georges J.F.Köhler
César Milstein
1974 – Theory of development and control of immune system
and discovery of principle of monoclonal antibody production

34. 1978 - Genetic principle of antibody diversity 1987
                               
Susumu Tonegawa
1939 -
Genetic principle of antibody diversity 1987

35. 1974 – Cell mediated immune response - MHC 1996
Peter Doherty
1940 -
Rolf M. Zinkernagel
1944 -
                                           
                                           
1974 – Cell mediated immune response - MHC 1996

38. NOSITELIA NOBELOVEJ CENY
ZA IMUNOLÓGIU
Mečnikov – fagocytóza
Boehring – pasívna imunizácia
Koch – oneskorená precitlivelosť
Bordet – objav komplementu
Ehrlich – humorálna imunita
Richet – opis anafylaxie
Burnet, Medawar – tolerancia
Porter, Edelman – štruktúra imunoglobulínov
Benacerraf, Dausset, Snell – MHC, regulácia IO
Doherty, Zinkernagel – MHC reštrikcia bunkami
sprostredkovanej protivírusovej
imnity
Jerne, Kohler, Milstein – formulácia teórie idiotyp. siete
1975 – monoklónové protilátky
Tonegawa – genetika protilátok

40. DEFINITIONS
Immunity - imunitas - v období Rímskej ríše znamenalo oslobodenie
senátorov od občianských povinností a
súdneho stíhania počas počas výkonu služby
- ochrana proti infekčným ochoreniam
- reakcia MAO proti cudzorodej hmote živej (MIO), či mŕtvej
(proteíny polysacharidy a pod.), bez ohľadu na fyziol. alebo
patol. dôsledky takejto reakcie