Antimicrobicia! & cytotoxic substances produced by activated macrophages can destroy phagocytosed microorganisms.
Mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils
Reactive oxygen intermediates
O2.- (Superoxide anion)
OH- (Hydroxide radicals)
H2O2 (Hydrogm peroxide)
ClO- (Hypochlorite anion)
Tumor necrosis factor -alpha
Reactive nitrogen intermediates
NO (nitric oxide)
NO2 (nitrogen dioxide)
HNO2 (nitrous oxide)
A) Oxygen-dependent killing mechanism:
- Activated phagocytes produce a number of "Reactive Oxygen Intermediates (ROIs)" & "reactive nitrogen intermediates" that have potent antimicrobial activity.
- During phagocytosis, a metabolic process known as the "Respiratory Burst" occurs in activated macrophages.
- Due to the respiratory burst, membrane - bound enzyme "Oxidase" will activate, that catalyzes the reduction of oxygen to superoxide anion (powerful oxidizing agent), a reactive oxygen intermediate & hydroxyl radicals &H2O2.
- As the lysosomes fuses with the phagosomes, the activity of "Myeloperoxidase" produces hypochlorite from hydrogen peroxide and chloride ions.
- Hypochlorite, the active agent of household bleach, is toxic to ingested microbes.
- When the macrophages are activated with bacterial cell wall components. The T-cell derived cytokine (IFN-γ), they begin to express high levels of “Nitric Oxide synthatase"(NOS), an enzyme that oxidizes L-arginine to yield L-Citrulline & nitric oxide (NO), a gas.
L-Arginine + O2 + NADPH -> NO + L-Citrulline +NADP+
- No has potent anti-microbial activity.
B) Oxygen-independent killing mechanism:
- Activated macrophages also synthesize 'lysozyme' and various hydrolytic enzymes whose degradative activities do not require Oxygen.
- The activated macrophages produce a group of antimicrobials cytotoxic peptides, commonly known as "Defensin", these Molecules are cystine- rich cationic peptides containing 29-35 Amino acids residues.
- The defensin is circularized protein.
- The peptide form ion-permeable channel in bacterial cell membrane.
- Some microorganism can survive & multiply within pathogens include:
- Listeria monocytogenes
- Salmonella typhimurium
- Neisseria gonorrhoeae &
- Mycobacterium aviutn
- Mycobacteriura tuberculosis
- Mycobacterium leprea
- Brucella abortus &
- Candida albicans
- Some intracellular pathogens prevent the fusion of lysosomes with phagosome and proliferate with in phagosomes.