After a pathogen binds to a particular PRR, the phagocyte must undergo several changes to allow for microbial killing.
This process begins by internalization of the bound pathogen into a phagosome. This phagosome fuses with other membrane-bound storage compartments within the cell. For example, neutrophils have lysosomes, primary granules and secondary granules that contain antimicrobial components. Macrophages only have lysosomes. The contents of these vesicles is outlined below:
| Vesicle | Contents |
|---|---|
| Lysosomes | Lysozyme Cathelicidin Acid hydrolases (elastase, proteases) |
| Primary granules | Myeloperoxidase Elastase Defensins |
| Secondary granules | Defensins Lactoferrin Lysozyme |
The fusion of the granules and lysosomes to the phagosome is mediated by calmodulin and SNARE proteins, which bring the vesicles together for fusion. After fusion of the antimicrobial components, NAPDH oxidase is assembled. At rest, the components of NADPH oxidase are found within the cytoplasm and in endosomal membranes. Once formed, NADPH oxidase transfers an electron to oxygen, forming superoxide (O₂⁻).
Superoxide is converted into hydrogen peroxide by superoxide dismutase, which allows it to be microbicidal. This process is called the respiratory burst. Hydrogen peroxide can also combined with other chemical components to produce other microbicides. These include hydroxyl radical (OH⁻) and hypochlorite (OCl⁻). Hypochlorite formation is mediated by myeloperoxidase, found in primary granules of neutrophils.
Other changes associated with phagolysosome fusion is induction of inducible nitric oxide synthase (iNOS), which produces nitric oxide. Hydrogen ions are also drawn into the phagolysosome in an attempt to neutralize superoxide. This increased hydrogen decreases the pH of the phagolysosome.
All of these antimicrobial activities are summarized below:
| Microbicidal Action | Product | Function |
|---|---|---|
| Acidification | Hydrogen influx after superoxide production | |
| Toxic oxygen-derived products | Nitric oxide Superoxide/hydrogen peroxide Hydroxyl radical Hypochlorite | Direct microbicidal activity |
| Antimicrobial proteins | Cathelicidin Defensins | Form pores in microbial membranes |
| Enzymes | Lysozyme Acid hydrolases | Break down proteins and elastins |
| Iron competition | Lactoferrin | Sequesters iron |
Zachary JF. Pathologic Basis of Veterinary Disease, Sixth Edition.
Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease, Tenth Edition.
Murphy KP, Janeway CA, Travers P et al. Janeway’s Immunobiology, Eighth Edition.
