Development and Nuclear Morphology
Cell morphology changes systematically during maturation. The primary diagnostic criterion is the shape of the nucleus.
- Band forms (juvenile): The nucleus is bean-shaped or indented (normally 0–0.5%).
- Stab forms (band): The nucleus resembles a horseshoe or an S-shaped curved rod (3–5%).
- Segmented forms (mature): The nucleus is divided into 3–4 lobes connected by thin chromatin strands. These constitute the vast majority of circulating cells.
An interesting feature is sexual dimorphism. In female segmented neutrophils, a Barr body (sex chromatin) can be detected, which appears as a small drumstick-like appendage on the nucleus. The cytoplasm of the mature cell contains few general-purpose organelles but is densely packed with specific granules. Neutrophils are incapable of mitosis as they are terminally differentiated cells.
Granule Classification
The cytoplasm of a mature neutrophil contains three types of granular structures, which differ in composition and function:
- Primary (azurophilic) granules. Comprise 10–20% of the total granule pool and are the largest. Functionally, they are lysosomes containing the marker enzyme myeloperoxidase, as well as defensins, cationic proteins, and elastase. They are essential for intracellular microbial killing.
- Secondary (specific) granules. The most abundant pool (about 80%). They are small and stain pinkish-purple. They contain lysozyme, alkaline phosphatase, collagenase, and lactoferrin. They mediate pathogen destruction both intracellularly and upon release into the extracellular environment.
- Tertiary granules. Less common (5–10%). They contain adhesion proteins and gelatinase, which degrades the extracellular matrix, facilitating cell migration through tissues.
Migration Mechanism into Tissues
Neutrophils perform their functions outside the vascular bed. The trigger for their emigration is local inflammation or tissue injury. Migration occurs through postcapillary venules in several stages:
- Rolling (reversible binding): The leukocyte tethers to the vascular endothelium and 'rolls' along the vessel wall under the force of blood flow.
- Firm adhesion: During inflammation, endothelial cells upregulate adhesion molecules in response to cytokines. The binding becomes irreversible, and the cell flattens.
- Diapedesis (transmigration): The neutrophil extends a pseudopodium and squeezes through the vessel wall (typically paracellularly, between endothelial cells).
Within tissues, the cell moves via rearrangement of actin cytoskeletal filaments. Directional movement is driven by chemotaxis—a gradient of chemical signals originating from the site of injury.
Bacterial Destruction and Pus Formation
Neutrophils act as microphages. Target recognition is most efficient via opsonization—when a bacterium is tagged with IgG antibodies, whose $F_c$ fragments are recognized by leukocyte receptors.
The process of intracellular killing proceeds as follows:
- A phagosome forms around the ingested bacterium.
- The phagosome fuses with specific granules and subsequently with azurophilic granules to form a unified phagolysosome.
- A 'respiratory burst' occurs—a rapid generation of reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical).
As a result of enzymatic attack and reactive oxygen species, the bacterium is killed and hydrolyzed. During massive phagocytosis, many neutrophils die, releasing aggressive enzymes into the extracellular space. Pus is formed at the site of inflammation from dead neutrophils, destroyed tissue, and lysed bacteria.