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Phagocytosis – Introduction and Mechanisms
- A significant defense mechanism of the innate system.
- Phagocytosis: Process of ingestion and digestion of the extracellular particulate material by phagocytic cells.
- Extracellular particulate includes complete microorganisms (pathogens), insoluble particles.
- Endogenous matter such as dead host cells, debris particles, and activated clotting factors are also phagocytosed.
- Phagocytic cells, which includes neutrophils, blood monocytes, and tissue macrophage.
Steps of Phagocytosis
- Macrophage is attracted towards chemotactic factors – this process is called chemotaxis.
- Bacteria or antigens become attached to membrane evaginations (pseudopodia).
- The ingested bacterium fused with pseudopodia is enclosed in the phagosome.
- Phagosomes lead toward the cell interior and fuse with lysosomes, form phagolysosomes.
- In phagolysosomes, ingested particles are digested by lysozyme.
- Digested particle releases from the cell by exocytosis.
Mechanism of Phagocytosis
- Macrophage is activated by classes of antibody-binding antigens, known as opsonins.
- Opsonins enhance the rate of phagocytosis.
- The process is called opsonization.
- Antimicrobial & Cytotoxic substances released by activated macrophage.
- Both substances have a tendency to destroy ingested microorganism
Oxygen-Dependent Killing Mechanisms
- Reactive oxygen intermediates (ROIs) & reactive nitrogen intermediates – produced by activated macrophages.
- Both reactive O2 & N2 intermediates have an effective antimicrobial effect.
- During phagocytosis, a process of respiratory burst occurs in macrophages
- In which, membrane-bound oxidase is activated
- Reduction of O2 —> catalyze ——> Superoxide anion( Reactive O2 intermediate)
- Superoxide anion generates hydroxyl radicals & hydrogen peroxide (oxidizing agents)
- In phagolysosome, the enzyme myeloperoxidase catalyze hydroperoxide and chlorine ions ——> Hypochlorite
- Hypochlorite is toxic to ingested microorganisms, therefore used in household bleach.
- Generally, the macrophage is triggered by Lipopolysaccharide(LPS)–> Component of the bacterial cell.
- For mycobacteria, muramyl dipeptide + T-cell derived cytokines (IFN-λ)—–>express nitric oxide synthetase (High levels)
- Enzyme nitric oxide synthetase —–> oxidize —–>L-arginine into—–> L-citrulline + nitric oxide (reactive N2 intermediates).
- Nitric oxide has efficient antimicrobial activity.
- Combination with superoxide ions generates more effective antimicrobial compounds.
Oxygen- Independent Killing Mechanisms
- Activated macrophages produce several hydrolytic enzymes and lysozymes.
- These enzymes have degradative activity, without the involvement of oxygen.
- Additionally, a group of peptides are produced, which have antimicrobial & cytotoxic activity known as defensins.
- Cysteine-rich molecules consist of 29-35 residues of amino acids.
- Form channels in the cell membranes of the bacteria, which are ion-permeable.
- Can kill, diversity of the bacteria which includes, E.Coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumonia.
- Cytokine such as tumor necrosis factor (TNF-α), is released by activated macrophage
- Have cytotoxic effects on tumor cells.
References and Sources