1. Phagocytosis endocytosis defense role profesional phagocytes

2. elimination - clearing - Phagocytosis activation other cells secretion enzymes, cytokines presentation Ag killing regulation Inflammation

3. Phagocytosis Professional Effective phagocytosis and secretion: »macrophages »neutrophil granulocytes Non- Professional Secretion »eosinophils »basophils »mast cells

4. Professional phagocytes macrophages (monocytes), neutrophils elimination of microbs, partiles membrane receptors –complement R: CR1, CR2 –receptors for Ab: Fc receptors

5. Mechanism 1) adhesion - endotel 2) diapedesis 3) chemotaxis 4) adhesion – bacteria,... (+ opsonisation) 5) ingestion 6) digestion (killing and degradation)

8. Adhesion endothelium - neutrophils NeutrophilEndothelial cellFunction Le x (CD15) sialyl-Lewis x antigen P-selectin (CD62P) rolling Integrins: CD11a (LFA-1) CD18 ICAM-1, 2 (CD54, CD102) adhézia CD11b (Mac-1) CD18 ICAM-1 adhézia

9. Adhesion endothelium - monocytes MonocytesEndothelial cell Function Integrins  1 (CD29)VCAM-1rolling CD11a (LFA-1) CD18 ICAM-1, 2 (CD54, CD102) adhézia CD11b (Mac-1) CD18 ICAM-1adhézia

10. Diapedesis and chemotaxis Diapedesis Chemotaxis - chemotaxins –exogenous: bacterial oligopeptides (FMLP), LPS, lipids –endogenous: C5a, Ba, fibrinopeptides, kalikrein, plasminogen activator, metabolites of arachidonic acid (LTB 4,...) Stimulation of chemotexis, but also adherence, endocytosis and sekretion of lysosomal enzymes.

12. Adhesion 1) surface molecules of particle 2) opsonins

13. Opsonins – immune phagocytosis Opsonisation: –opsonins (specific molecules) –facilitation of adhesion –principle – opsonins represent ligands for receptors of phagocytes

14. Phagocytosis Immune opsonins Non-immune

15. Opsonins – immune phagocytosis ReceptorOpsonin (ligand) Cells CR1C3b, C4bneutrophils, monocytes, B cells, some T cells CR2C3bneutrophils, monocytes, macrophages, B cells FcRAb: IgG, IgM monocytes, macrophages, neutrophils

16. Opsonins C3b Ab Phagocytes - receptors Bactetia + opsonins CR3 FcR

17. Ingestion - digestion Ingestion >>> pseudopodia – phagozómu. Digestion >>> lysosom –phagolyzozóm. Lysosoms >>> enzymes Role > killing and destruction.

18. Microbicidal mechanisms 1) Oxygen dependent 2) Oxygen independent

19. Microbicidal mechanisms Oxygen dependent Myeloperoxidase independent - hydrogenperoxide - superoxide anion - hydroxyl radical - singlet oxygen 2)Myeloperoxidase (MPO) dependent - MPO + hydrogenperoxide + I - - MPO + hydrogenperoxide + Cl -

20. Respiratory burst Antimicrobial molecules Process: - stimulation of phagocytes (mikroorganizmy, C5a, Ag+Ab,...) - oxygen consuption - anaerob. metabolism - superoxide

21. Respiratory burst

22. MPO mechanisms

23. Oxygen independent mechanism - low pH in phagolysosome - cationic proteins - defensines - bactericidal proteins - lysozyme - neutral proteinases - lactoferin - phospholipase A2 - histones (leukin)

24. Deficiences 1.Low number of phagocytes a. Kostmann syndrom – inherited agranulocytosis –infections of skin and mucosa b. Cyklic neutropenia – every 3rd week Failure of function 2. Failure of function a. CGD (Chronic granulomatous disease) - defect of NADPH-oxidase - X chromosome – linked decreased bactericidal activity - recurent pyogenic infections staphylococcal infections - pneumonia

25. Deficiences b. LAD (Leukocyte Adhesion Deficiency) - failure of adhesins on phagocyte - ↓ expresion of β2 subunit of integrins (CD18) Phagocytes: - do not adhere to endothelial cells - absent in the site of inflammation - recurent skin infections - wound healing - candidiasis