Zipper%20Mechanism

1
(No Transcript)
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.

4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
Salmonellosis

• Factors for disease
• Pathogen Virulence?
• Host Immune function?
• Environment Dose?

http//www.worldwidevaccines.com/typhoid/typhoid_4
.jpg
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.

10
(No Transcript)
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
• 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.

14
(No Transcript)
15
(No Transcript)
16
(No Transcript)
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!

18
(No Transcript)
19
Does all this talk of phagocytosis make you
hungry?
The End
http//www.sph.tulane.edu/7Edmsander/WWW/Video/Ma
cmov.html