1. Immunity to microbes (mechanisms of defense against
bacterial infections)

2. Goal To understand basic principles of defense against
infections induced by:
bacteria
- extracellular
- intracellular
viruses
parasites
protozoa
helmints
fungi

3. Important features of defense against
infectious agents
Mediated by the mechanisms of both innate and
adaptive immunity
Specialization of the immune system allows optimal
response to each type of microbe
Establishment, course and outcome of infection depend on
ability of pathogen to evade or resist immune response
Tissue injury and disease are often result of immune response to pathogens

4. Bacteria Unicellular prokaryotes Survive and replicate:
- outside cell (extracellular bacteria)
- inside cell (intracellular bacteria)
Induce disease by:
- induction of inflammation
- production of toxins

5. Extracellular bacteria
Replicate outside cell (in circulation, tissues
and lumens)
Induce inflammation (often with pus formation)
- e.g. staphylococci and streptococci
Produce toxins:
- exotoxins (diphteria, tetanus...)
- endotoxin (LPS)

6. Mechanisms of defense against extracellular bacteria
Mechanisms of innate immunity
- complement activation by alterative and lectin pathway
- phagocytosis (neutrophils and macrophages)
- inflammation (induction of TNF, IL-1, chemokines etc.)

7. Complement activation by alterative and lectin pathway

8. Phagocytosis and killing of microbes
Pathogen recognition

9. Phagocytosis and killing of microbes
Zipping of membrane
around microbe

10. Phagocytosis and killing of microbes
Ingestion of microbe

11. Phagocytosis and killing of microbes
Fusion of phagosome
with lysosome

12. Phagocytosis and killing of microbes
Phagocyte activation

13. Phagocytosis and killing of microbes

14. Inflammation

15. Mechanisms of defense against extracellular bacteria
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- complement activation by clasical pathway (IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
CD4+ helper T cells

16. Mechanisms of defense against extracellular bacteria
(B cells)

17. Neutralization of toxins

18. Opsonization and phagocytosis

19. Mechanisms of defense against extracellular bacteria
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- complement activation by clasical pathway(IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
CD4+ helper T cells
- B cell help (various citokines)
- macrophage activation (IFN-γ) – TH1
- neutrophil activation (IL-17) – TH17
- induction of inflammation (TNF)

20. Macrophage stimulation Eosinophil stimulation Neutrophil stimulation
TH1
IFN-
Naivna CD4+T
Naïve CD4+T
IL-4
IL-5
Eosinophil
stimulation
TH2
Neutrophil
stimulation
TH17
IL-17A

21. Defence against intracellular pathogens TH1
Naivna CD4+T
Naïve
CD4+T
Defence against helmints
TH2
Defence against some extracellular bacteria and fungi
TH17

22. Mechanisms of defense against extracellular bacteria
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)

24. Mechanisms of defense against extracellular bacteria
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)
- genetic variation of surface antigens (Neisseria sp, E. coli...)
- inhibition of complement activation (many bacteria)
- production of IgA proteases (Neisseria sp., S. pyogenes...)

25. Mechanisms of defense against extracellular bacteria
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)

26. Mechanism of superantigen action
T-cell
Activation of 5-20% T cells
Massive cytokine production
Antigen-presenting cell

27. Mechanisms of defense against extracellular bacteria
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)
- “molecular mimicry” (S. pyogenes and Rheumatic fever)

28. Intracellular bacteria
Survive and replicate in cells
Enter cells via receptors or phagocytosis
Escape from antibody, complement etc.
Induce chronic infections
Facultative intracellular (e.g. Mycobacterium sp.)
Strict intracellular (Chlamydia and Ricketsia)

29. Intracellular bacteria

30. intracellular bacteria
Mechanisms of defense against
intracellular bacteria
Mechanisms of innate immunity
- phagocytosis (inefficient unless stimulated)
- NK cells (production of IFN-γ and stimulation of macrophages)

31. Stimulation of macrophages by NK cells

32. Mechanisms of defense against intracellular bacteria
Mechanisms of adaptive immunity
Cell-mediated immunity
CD4+ helper T cells (TH1)
- B-cell help to produce opsonizing antibodies (IFN-γ)
- macrophage activation (IFN-γ) – TH1
- induction of inflammation (TNF)
CD8+ cytotoxic T cells

33. Macrophage activation by
TH1 cells

34. Mechanisms of defense against intracellular bacteria
Mechanisms of aquired immunity
Cell mediated immunity
CD4+ helper T-cells (TH1)
- Support of B-cells to produce opsonizing antibodies (IFN-γ)
- Macrophage activation (IFN-γ) – TH1
- Induction of inflammation (TNF)
CD8+ cytotoxic T-cells
- destruction of infected cells (containing bacteria in cytoplasm)

35. Cooperation between CD4+ and CD8+ T-cells in elimination of
intracellular bacteria

36. Mechanisms of defense against intracellular bacteria

37. Mechanisms of defense against intracellular bacteria
Mehanisms of immune evasion
- inhibition of phagolysosome formation (M. tuberculosis...)

38. Mechanism of immune evasion
by Mycobacteria

39. Mechanisms of defense against intracellular bacteria
Mehanisms of immune evasion
- inhibition of phagolysosome formation (M. tuberculosis...)
- escape from phagolysosome (L. monocytogenes....)
- inhibition of ROS i NO (M. leprae...)

40. Mechanisms of defense against intracellular bacteria
Injurious effects of immune response
chronic inflammation (DTH) and granuloma formation
(tuberculosis)

43. Thanks for your attention!
Questions?