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Ph agocyt osis

Ph agocyt osis. e ndocyt osis defense role profesional phagocytes. Phagocytosis. Phagocytosis. elimination - clearing -. killing. presentation Ag. Inflammation. secretion enzymes, cytokines. activation other cells. regul ation. Phagocytosis. Professional

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Ph agocyt osis

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  1. Phagocytosis • endocytosis • defense role • profesional phagocytes

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

  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)

  6. Adhesion endothelium - neutrophils

  7. Adhesion endothelium - monocytes

  8. 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.

  9. Adhesion • 1) surface molecules of particle • 2) opsonins

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

  11. Phagocytosis Immune opsonins Phagocytosis Non-immune

  12. Opsonins – immune phagocytosis

  13. CR3 C3b FcR Ab Opsonins Phagocytes - receptorsBactetia + opsonins

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

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

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

  17. Respiratory burst • Antimicrobial molecules • Process: - stimulationof phagocytes (mikroorganizmy, C5a, Ag+Ab,...) - oxygen consuption - anaerob. metabolism - superoxide

  18. Respiratory burst

  19. MPO mechanisms

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

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

  22. 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

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