1. Introduction to Immunology
Martin Liška

2. The immune system and its importance for homeostasis of organism
The immune system = a system of non-specific and specific mechanisms protecting the organism from damage caused by infectious factors of environment and providing surveillance of own structures (elimination of damaged and death cells)
The aim is maintenance of homeostasis and integrity of macroorganism

3. Mechanisms of immune system and their cooperation
1/ Innate (non-specific) immune system
innate, not developed after the exposition to infection
uniform response, prompt, no immunological memory
mechanical barriers (mucosa, skin)
phagocytic cells (microphages, macrophages)
acute phase proteins (CRP)
complement system

4. Mechanisms of immune system and their cooperation
2/ Adaptive (specific) immune system
adaptability, developed after the exposition to infection
the immune response is not inherited, immunological response
B and T cells, immunoglobulins

5. The components of immune system
1/ Cells
a/ innate immune system
neutrophils, eosinophils, basophils
macrophages
nature killer cells (NK cells)
b/ adaptive immune system
- lymphocytes

6. The components of immune system
2/ Organs
liver, skin etc.
primary lymphoid organs – bone marrow, thymus
- secondary lymphoid organs - spleen, lymph nodes, mucus associated lymphoid tissue (MALT)

7. The components of immune system
3/ Substances
The complement system
Cytokines – molecules which ensure the communication between the components of immune system (e.g.IFN, IL, growth factors)
Acute phase proteins (CRP, MBL)
Hormones (immunostimulatory/immunesuppressive effects)
Immunoglobulins

8. The immune system of mucosa and skin
intact surface, clearance of surface (microcillia, saliva, tears, urine)
lysozyme
IgA
lymphoid tissue of mucosa (MALT)
macrophages (dendritic cells)

9. The immune system of mucosa and skin
intact surface
lipid barrier (eczema)
immunocytes of the skin (e.g. Langerhans cells)

10. Non-specific immune mechanisms
1/ Barriers
see above (skin, mucosa)
secretions (fatty acids, HCl, lysozyme)
2/ Various physiological mechanisms
body temperature
hormones

11. Non-specific immune mechanisms
3/ Phagocytosis
the process by which particular substances or cells are ingested and destroyed by specialized cells
neutrophils, macrophages (monocytes, tissue macrophages)

12. Neutrophils The most abundant population of leucocytes (cca 70%)
Granulocytes
They stain a neutral pink when stained by H&E
Nucleus divided into 2-5 lobes, cytoplasm with granules
Neutrophils participate in defense against extracellular pathogens

13. Neutrophils The average half-life in circulation is about 12 hours
Upon activation, they marginate (position adjacent to the endothelium) → rolling (selectins) → adhesion to endothelium (integrins) → diapedesis (integrins) → chemotaxis (movement toward sites of inflammation by cytoplasmic streaming in response to chemotaxins (IL-8, IFN-g, C5a) → binding to microbe

14. Neutrophils - phagocytosis
Interaction with some surface molecules of microbes (PAMPs, lectin interactions, binding of TLR to some surface molecules of microorganisms)
Opsonisation (= enhancement of binding of phagocytes to microbes) – Ig, complement system components, CRP, MBL

15. Neutrophils - phagocytosis
Surrounding of microorganism → forming of vacuole (phagosome) → fusion with the lysosome → phagolysosome
Phagosome formation depends on contractile proteins action

16. Neutrophils – intracellular destruction of microbes
1/ Oxygen independent systems
substances that are contained in granules
myeloperoxidase, lysozyme, alkaline phosphatase, lactoferrin → hydrolysis microbe’s cell wall components
defensins → forming of channels in microbial cell membrane

17. Neutrophils – intracellular destruction of microbes
2/ Oxygen-dependent systems
Respiratory burst
NADPH oxidase system → production of reactive oxygen agents (hydrogen peroxide, superoxide anion, singlet oxygen, hydroxyl radicals)
Disorder of this system in CGD

18. Neutrophils – intracellular destruction of microbes
2/ Oxygen-dependent systems
Myeloperoxidase, in the presence of toxic oxygen metabolites, catalyzes peroxidation of surface molecules on microorganisms

19. Macrophages
Intracellular destruction of microorganisms mainly by NO synthase (system stimulated by the action of IFN-g or TNF)
Production of numerous substances: lysozyme, some components of the complement system, oxygen metabolites (H2O2, NO), cell function regulators (IL-1, IFN-a), arachidonic acid metabolites, endogenous pyrogens

20. Natural killer cells
Granular lymphocytes, different from T- and B-lymphocytes
Cytotoxicity to tumor cells and virally infected autologous cells (perforins)
Play a role in defense against some bacterial, fungal and helminthic diseases
Participate in reactions of antibody-dependent cell- mediated cytotoxicity (ADCC)
They are not subject to MHC restriction (= NK-cells do not need to recognize MHC molecules in the target cells)

21. Natural killer cells
They kill target cells by perforins (formation of channels, abnormal ion flux, depolarization, essential metabolite leakage, cell destruction)
NK cells are protected against perforins by specialized cell membrane protein (protectin)

22. Interferons Proteins that induce antiviral activity in cells
We can distinguish two types:
a/ type I: IFN-a (macrophages and other
cells)
IFN-b (fibroblasts)
b/ type II: IFN-g (T-lymphocytes)

23. Function of interferons
Stimulation of cell production of antiviral proteins (protein kinase, oligonucleotide polymerase – interference with the translation of viral mRNA)
Enhancement of T-cell activity
Activation of macrophages
Enhancement of NK cells cytotoxic action

24. Adaptive immune mechanisms
1/ Humoral
generation of antibodies (Ig) – B cells (plasma cells)
in majority of antigens, the cooperation with T helper cells is necessary
2/ Cell-mediated
generation of antigen-specific T cells (helper, cytotoxic)
antigen presentation is necessary

25. Adaptive immune mechanisms
Antibodies → neutralization and opsonization (specific „adapter“) of microbes, complement system activation
T cells → cytotoxic effects to microbes, help for B cells, macrophages activation, cytokines

26. Innate/adaptive immune mechanisms
Innate (non-specific) immune system: prompt reaction x less effective, less directed
Adaptive (specific) immune system: slower development of reaction x more effective, more directed, immunological memory
Both systems cooperate (complement system is activated by IC, cytokines recruit other cells to the site of reaction, antigen presentation)