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PHAGOCYTOSIS- OXYGEN
INDEPENDENT KILLING
MECHANISM
PRESENTED BY
R.PRATHISHA
MFT16087(AAH)
Oxygen-independent activity
• Lysosomal granules contain a variety of
extremely basic proteins that strongly inhibit
bacteria, yeasts and even some viruses.
• A few molecules of any one of these cationic
proteins appear able to inactivate a bacterial
cell by damage to their permeability barriers,
but their exact modes of action are not
known.
• The lysosomal granules of neutrophils
contain lactoferrin, an extremely powerful
iron-chelating agent, which withholds
potential iron needed for bacterial growth.
• The pH of the phagolysosome may be as low
as 4.0 due to accumulation of lactic acid,
which is sufficiently acidic to prevent the
growth of most pathogens.
• This acidic environment apparently optimizes
the activity of many degradative lysosomal
enzymes including lysozyme, glycosylases,
phospholipases, and nucleases.
Bacterial glycolipids. Glycosyl diglycerides in gram-positive bacteria.
Glycosylases are enzymes that hydrolyze glycosyl compounds.
In turn, glycosylases are divided into two groups: glycosidases--
enzymes that hydrolyze O- and S-glycosyl compounds -- and
enzymes that hydrolyze N-glycosyl compounds.
A phospholipase is an enzyme that
hydrolyzes phospholipids[1] into fatty acids and
other lipophilic substances. There are four major classes,
termed A, B, C and D, distinguished by the type of reaction
which they catalyze:
phagocyte function are
(1) the arachidonic acid (AA) released by phospholipase
A2 (PLA2),
(2) inositol trisphosphate (IP3) released by
phosphatidylinositol-specific phospholipase C (PI-PLC), and
(3) diacylglycerol (DAG) produced directly by PI-PLC or by the
sequential action of phospholipase D (PLD) and
phosphatidate phosphohydrolase (PAP) on
phosphatidylcholine (PC).
In contrast to these compounds which support phagocytosis, the
ceramide product of sphingomyelinase may provide a brake,
inhibiting PLD and terminating ingestion.
MPO catalyzes the H2O2-mediated oxidation of chloride to form
HOCl, which reacts with the bacterium (yellow) or neutrophil
proteins to produce cytotoxic chloramines [monochloramine
(NH2Cl) and protein chloramine (PNHCl)].
•In addition, activated macrophages produce a group of
antimicrobial and cytotoxic peptides, commonly known as
defensins.
•Cathepsin G is an example for defensins.
•These molecules are cysteine-rich cationic peptides containing 29–
35 amino-acid residues.
•Each peptide, which contains six invariant cysteines, forms a
circular molecule that is stabilized by intramolecular disulfide
bonds.
DEFENSINS
•These circularized defensin peptides have been shown to
form ion-permeable channels in bacterial cell
membranes.
Defensins can kill a variety of bacteria, including Staphylococcus
aureus, Streptococcus pneumoniae, Escherichia
coli, Pseudomonas aeruginosa, and Haemophilus influenzae.
Exocytosis:
Finally the killed organisms are digested by hydrolytic
enzymes and the degraded products are released to the
exterior by the process of exocytosis.
Phago oxygen indepenedent killing mechanism

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Phago oxygen indepenedent killing mechanism

  • 2.
  • 3. Oxygen-independent activity • Lysosomal granules contain a variety of extremely basic proteins that strongly inhibit bacteria, yeasts and even some viruses.
  • 4.
  • 5. • A few molecules of any one of these cationic proteins appear able to inactivate a bacterial cell by damage to their permeability barriers, but their exact modes of action are not known.
  • 6. • The lysosomal granules of neutrophils contain lactoferrin, an extremely powerful iron-chelating agent, which withholds potential iron needed for bacterial growth.
  • 7. • The pH of the phagolysosome may be as low as 4.0 due to accumulation of lactic acid, which is sufficiently acidic to prevent the growth of most pathogens.
  • 8. • This acidic environment apparently optimizes the activity of many degradative lysosomal enzymes including lysozyme, glycosylases, phospholipases, and nucleases.
  • 9.
  • 10. Bacterial glycolipids. Glycosyl diglycerides in gram-positive bacteria. Glycosylases are enzymes that hydrolyze glycosyl compounds. In turn, glycosylases are divided into two groups: glycosidases-- enzymes that hydrolyze O- and S-glycosyl compounds -- and enzymes that hydrolyze N-glycosyl compounds.
  • 11. A phospholipase is an enzyme that hydrolyzes phospholipids[1] into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:
  • 12. phagocyte function are (1) the arachidonic acid (AA) released by phospholipase A2 (PLA2), (2) inositol trisphosphate (IP3) released by phosphatidylinositol-specific phospholipase C (PI-PLC), and (3) diacylglycerol (DAG) produced directly by PI-PLC or by the sequential action of phospholipase D (PLD) and phosphatidate phosphohydrolase (PAP) on phosphatidylcholine (PC).
  • 13. In contrast to these compounds which support phagocytosis, the ceramide product of sphingomyelinase may provide a brake, inhibiting PLD and terminating ingestion.
  • 14. MPO catalyzes the H2O2-mediated oxidation of chloride to form HOCl, which reacts with the bacterium (yellow) or neutrophil proteins to produce cytotoxic chloramines [monochloramine (NH2Cl) and protein chloramine (PNHCl)].
  • 15. •In addition, activated macrophages produce a group of antimicrobial and cytotoxic peptides, commonly known as defensins. •Cathepsin G is an example for defensins. •These molecules are cysteine-rich cationic peptides containing 29– 35 amino-acid residues. •Each peptide, which contains six invariant cysteines, forms a circular molecule that is stabilized by intramolecular disulfide bonds. DEFENSINS
  • 16. •These circularized defensin peptides have been shown to form ion-permeable channels in bacterial cell membranes.
  • 17. Defensins can kill a variety of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Haemophilus influenzae. Exocytosis: Finally the killed organisms are digested by hydrolytic enzymes and the degraded products are released to the exterior by the process of exocytosis.

Editor's Notes

  1. Activated macrophages also secrete tumor necrosis factor (TNF), a cytokine that has a variety of effects and is cytotoxic for some tumor cells. Lactoferin chelates iron from the medium and prevent the growth and proliferation of iron dependent bacteria.  Lysozyme splits mucopeptide in bacterial cell wall and lysed bacteria.