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Zipper Mechanism

Zipper Mechanism. Ingestion occurs by sequential engagement of the phagocyte membrane with the particle surface. Pseudopod advance proceeds no further than the receptor-ligand interaction permits. TRIGGER MECHANISM. Particle binding initiates an ‘all or none’ phagocytic response.

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Zipper Mechanism

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  1. Zipper Mechanism • Ingestion occurs by sequential engagement of the phagocyte membrane with the particle surface. Pseudopod advance proceeds no further than the receptor-ligand interaction permits.

  2. TRIGGER MECHANISM • Particle binding initiates an ‘all or none’ phagocytic response.

  3. Salmonellosis Factors for disease: Pathogen – Virulence? Host – Immune function? Environment – Dose? http://www.worldwidevaccines.com/typhoid/typhoid_4.jpg

  4. Salmonella Virulence • SPI-1: TTSS to deliver effector proteins to cytoplasm that induce cytoskeletal rearrangments to facilitate Salmonella uptake in SCV. • SPI-2: TTSS to deliver effector proteins from SCV to cell cytoplasm that induce focal actin condensation around SCV. • spv: prevents actin polymerization needed for F-actin filament formation.

  5. SIGNALS FROM OUTSIDE • How to invade non-phagocytic cells? • SPI-1 TTSS: • Activate regulators Cdc42 and Rac1 in host. • Bacteria-host interaction to promote polymerization and bundling of actin filaments. • Restore normal actin dynamics after invasion.

  6. MEMBRANE RUFFLING Ruffles, Macropinocytosis, Engulfment: • Sop B, E, E2 activate GTPases Cdc42, Rac1. • Activate WASP, Scar/Wave, Arp2/3 to initiate actin polymerization. • Translocate: • SipC – Insert in target cell membrane, direct filament formation at sites adjacent to bacteria? • SipA – ‘Molecular staple’ to stabilize actin filaments. • SptP – Reverse cytoskeletal rearrangements.

  7. SIGNALS FROM INSIDE • How to proliferate within cells? • SPI-2 TTSS: • Translocate effectors from SCV to cytoplasm: • Form filamentous endosomes • Decrease recruitment of NADPH oxidase • Change SCV fusion pathway • VAP formation of actin around SCV • SpvB: • Depolymerizes actin from F filaments to G monomers with ADP ribosylation.

  8. TIMING IS EVERYTHING • Events are carefully orchestrated: • Focal actin polymerization for cell invasion. • Caused by SPI-1 effectors • Reversed by SptP • Focal actin condensation for effects from SCV. • Caused by SPI-2 effectors • Reversed by SpvB • Depolymerization leads to apoptosis and further Salmonella phagocytosis!

  9. Does all this talk of phagocytosis make you hungry? The End http://www.sph.tulane.edu/%7Edmsander/WWW/Video/Macmov.html

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