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Phagocytosis = basic tool of innate immune respons phagocyting cells steps of phagocytosis Phagocyting Cells neutrophile granulocytes destroying of extracellular bacteria, short lived cells, pus forming cells Monocytes / macrophages destroying of self cells and intratracellular micoroorganism, long lived cells presentation of antigen to T cells dendritic cells presentation of antigen to T cells The granulocytes often take the first stand during an infection. They attack any invaders in large numbers, and "eat" until they die. The pus in an infected wound consists chiefly of dead granulocytes. The macrophages ("big eaters") - start out as white blood cells called monocytes. Monocytes that leave the blood stream turn into macrophages. - are slower to respond to invaders than the granulocytes, but they are larger, live longer, and have far greater capacities. - play a key part in alerting the rest of the immune system (adaptive immunity) The dendritic cells are "eater" cells and devour intruders, like the granulocytes and the macrophages. And like the macrophages, the dendritic cells help with the activation of the rest of the immune system. They are also capable of filtering body fluids to clear them of foreign organisms and particles. Localised Forms of Macrophages Steps of Phagocytosis migration to the site of inflammation recognition of the antigen ingestion destroying of the pathogen presentation of the antigen Migration to The Site of Inflammation Neutrophils and monocytes: in circulation 7 % in bone marrow 93% ratio is changed in inflammation Migration to The Site of Inflammation rolling along the vessel wall contact between phagocyte and endothelial cell = adhesion passing through the vessel wall (diapedesis, extravasation) migration in tissue = chemotaxis Adhesion molecules (AM) a4/b1/VCAM-1 PSGL1/P-selectin L-selectin rolling CD18/ICAM-1 a4/b1/VCAM-1 adhesion diapedesis Contact of Phagocyte and Endothelium Adhesion Molecules endothelium phagocytes selectins + sacharid structrures of neutrophil (sialyl Lewis antigen) = rolling ICAM-1 + β 2 integrins (CD 11/CD 18) of neutrophils VCAM-1 + β 1 integrins of monocytes The Adhesion The Moving in Tissue = Chemotaxis Receptors for chemotactic factors: IL-8 C3a, C5a leucotrien B4 platelet activating factor (PAF) bacterial proteins (fMLP) Diapedesis and Chemotaxis Immune Recognition PAMPs pathogen associated molecular patterns DAMPs damage associated molecular patterns PRRs pattern recognition receptors of phagocytes PAMPs pathogen associated molecular patterns conserved in evolution shared by a large group of infectious agents clearly distinguishable from self pattern Gram-negative Gram-positive Yeast lipopolysacharide lipoteichoic acid cell wall mannans PRRs (pattern recognition receptors) of phagocytes lectins = proteins able to bind carbohydrates mannose and galactose receptor toll-like receptors TLR1 – TLR10 CD14 scavenger receptors for lipopolysacharides OPSONISATION = making tasty for the eater, „ spice“ receptors of phagocytes for antibodies (binding Fc fragment) complement C3 Diapedesis and Chemotaxis The Ingestion The adherence: PRR and PAMP Pseudopods around the particle: interaction of receptors and activating an actin and myosin contractile system Plasma membrane is completly around: the vacuole = phagosome phagosome + lysosom = phagolysosom Steps of Phagocytosis Microbicidal Mechanisms oxygen independent: antimicrobial proteins (defensins) enzyms (cathepsin, lysozym, lactoferrin) oxygen dependent: catalyzed by NADPH oxidase: NADPH + O2 = NADP + superoxide anion O2-, reactive oxygen radicals myeloperoxidase, halogenating system nitric oxide Presentation of The Antigen fragments of an antigen bind to MHC molecules on the surface of phagocyting cell = antigen presenting cell (APC) APC presents the antigens fragments to T cells T cells help B cells to produce specific antibodies, activate specific cytotoxic T cells cooperation between innate and adaptive immunity Presentation of Antigen http://www.youtube.com/watch?v=suCKm97y vyk http://www.youtube.com/watch?v=I9zSe0qm XGw.