1. (mechanisms of defense against viral, parasitic and fungal infections)
Immunity to microbes
(mechanisms of defense against viral, parasitic and fungal infections)

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

3. Viruses Simple structure (subcellular level)
Obligate intracellular agents
- unable to replicate outside cells
- enter cells via receptors
Induce diseases through
- damage of cells in which they replicate
- induction of immune response
Infections
- acute
- chronic (active and latent)

4. Mechanisms of defense against viruses
Mechanisms of innate immunity
inhibition of infection and induction of antiviral state
type I interferons (IFN-α and β)
- killing of infected cells (NK cells)

5. Antiviral action of type I interferons
Uninfected
cells
Infected
cells
Expression of
class I MHC molecules
Expression of
enzimes that inhibit viral replication
Protection from
infection
Killing of infected cells by CTLs

6. Destruction of infected cells by NK cells

7. Destruction of infected cells by NK cells

8. Destruction of infected cells by NK cells

9. Mechanisms of defense against viruses
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG)
Cell-mediated immunity

10. Neutralization of viruses

11. Protective mechanisms of antibodies

12. Mechanisms of defense against viruses
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG)
Cell-mediated immunity
CD8+ and CD4+ T cells
- killing of infected cells (CD8+ T cells)
- activation of CD8+ T cells and and B cells (CD4+ helper T cells)

13. Mechanism of killing by CTLs

14. Mechanism of killing by CTLs

15. Mechanism of killing by CTLs

16. Mechanism of killing by CTLs

17. Mechanism of killing by CTLs

18. Mechanism of killing by CTLs
perforin
granzymes
Target cell
CD8+ CTL
apoptosis

19. Mechanism of killing by CTLs
Target cell
CD8+ CTL
apoptosis
FasL
Fas

20. Mechanisms of innate and adaptive immunity
against viruses

21. Mechanisms of defense against viruses
Mechanisms of immune evasion
- antigenic variation (influenza virus, HIV...)

22. Antigenic variations of influenza virus

23. Mechanisms of defense against viruses
Mechanisms of immune evasion
- antigenic variation (influenza virus, HIV...)
- inhibition of antigen processing and presentation (many viruses)

24. Inhibition of antigen processing and presentation by viruses

25. Mechanisms of defense against viruses
Mechanisms of immune evasion
- antigenic variation (influenza virus, HIV...)
- inhibition of antigen processing and presentation (many viruses)
- inhibition of immune response (many viruses)

26. Inhibition of immune response through production of
virokines and viroreceptors

27. Mechanisms of defense against viruses
Mechanisms of immune evasion
- antigenic variation (influenza virus, HIV...)
- inhibition of antigen processing and presentation (many viruses)
- inhibition of immune response (many viruses)
- infection of immune cells (HIV...)
- establishment of latency (HSV, HIV...)
- inhibition of apoptosis (Herpes and Pox viruses...)

28. Mechanisms of defense against viruses
Injurious effects of immune response
- tissue damage due to CD8+ CTL activity (HBV...)
- immune complexes formation (HBV...)
- „molecular mimicry” (many viruses and various autoimmune diseases)

29. Parasites - complex eukaryotic organisms
- most common infectious diseases (30% of world population)
- complex life cycles
- protozoa (unicellular) – intra- and extracellular agents
- helmints (multicellular warms) – extracellular agents
- often induce chronic infections
- constant exposure (endemic areas)
- direct exposure or via vectors
- need for vaccines (immunoparasitology)

30. Mechanisms of defense against parasites Mehanisms of innate immunity
Protozoa and helmints – mostly resistant
- complement and phagocytosis (protozoa)
- eosinophils and macrophages (helmints)

31. Mechanisms of defense against parasites Mehanisms of adaptive immunity
Protozoa
B-cells, CD4+ TH1 and CD8+ T cells
- antibodies (B-cells) – Entamoeba sp., Plasmodium sp.
IFN-γ production and macrophage stimulation (CD4+TH1 cells) - Leishmania sp.
- cytotoxicity (CD8+ T cells) – Plasmodium sp.
Helmints
B-cells and CD4+ TH2 cells
- stimulation of B-cells to produce IgE (IL-4)
- stimulation of eosinophils (IL-5 and IgE)
- degranulation of mast cells (IgE)

32. Immunity against helmints
(TH2 response)

33. Immunity against helmints
(function of eosinophils)

34. Mechanisms of defense against parasites
Injurious effect of immune response
- granuloma formation and fibrosis (Schistosoma sp.)
- immune complex formation (Plasmodium sp.)
Mechanisms of immune evasion
- existence of different forms/stages (Plasmodium sp...)
- alteration of surface antigens (Trypanosoma sp....)
- complement resistance (many parasites)
-“concealing” – cysts (Toxoplasma sp.), residence in gut (intestinal parasites)

35. Fungi extracellular agents (some survive phagocytosis)
- yeast (unicellular)
- molds (multicellular)
- local and systemic mycoses
most systemic infection - opportunistic
some endemic (dimorphic fungi)
- risk factor - immunodeficiency (neutropenia)

36. Mechanisms of defanse against fungi Mechanisms of innate immunity
Fungi – mostly susceptible
- phagocytosis (neutrophils)
- complement
Mechanisms of adaptive immunity
Cell-mediated immunity
- macrophage and neutrophil activation (CD4+ TH1 and TH17 cells)
Injurious effect of immune response
- granuloma formation and fibrosis (Histoplasma capsulatum)
Mechanisms of immune evasion
- inhibition of phagocytosis (C. neoformans...)

37. Thanks for your attention!
Questions?