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Zipper Mechanism Ingestion occurs by sequential engagement of the phagocyte membrane with the particle surface. Pseudopod advance proceeds no further.

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Presentation on theme: "Zipper Mechanism Ingestion occurs by sequential engagement of the phagocyte membrane with the particle surface. Pseudopod advance proceeds no further."— Presentation transcript:

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2 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.

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

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8 Salmonellosis Factors for disease: Pathogen – Virulence?
Host – Immune function? Environment – Dose?

9 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.

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11 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.

12 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.

13 SIGNALS FROM INSIDE How to proliferate within cells? SPI-2 TTSS: SpvB:
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.

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17 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!

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19 Does all this talk of phagocytosis make you hungry?
The End


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