Development and nuclear structure
Cell morphology changes systematically as it matures. The main diagnostic criterion is the shape of the nucleus.
- Band forms (metamyelocytes/immature): the nucleus is kidney-shaped (normally accounting for 0–0.5%).
- Band neutrophils: the nucleus resembles a horseshoe or an S-shaped curved rod (3–5%).
- Segmented neutrophils (mature): the nucleus is divided into 3–4 segments connected by thin strands. These constitute the bulk of the cells.
An interesting feature is sexual dimorphism. In women, Barr body (sex chromatin) can be found in the nucleus of a segmented neutrophil, appearing as a small "drumstick"-like protrusion. 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.
Classification of granules
Three types of granular structures are distinguished in the cytoplasm of a mature neutrophil, differing in composition and function:
- Primary (azurophilic) granules. Account for 10–20% of the total number and are the largest. Essentially, these are lysosomes containing the marker enzyme myeloperoxidase, as well as defensins, cationic proteins, and elastase. They are essential for intracellular destruction of microbes.
- Secondary (specific) granules. The most abundant pool (about 80%). Small, staining purple-pink. Contain lysozyme, alkaline phosphatase, collagenase, and lactoferrin. Responsible for destroying pathogens both intracellularly and upon release into the extracellular environment.
- Tertiary granules. Encountered rarely (5–10%). Contain adhesion proteins and gelatinase, which breaks down the extracellular matrix, paving the way for the cell during migration into tissues.
Mechanism of migration into tissues
Neutrophils perform their functions outside the vascular bed. The trigger for their exit is local inflammation or tissue damage. Migration occurs through postcapillary venules in several stages:
- Rolling (reversible binding). The leukocyte attaches to the vascular endothelium and "rolls" along its wall under the force of blood flow.
- Firm adhesion. During inflammation, endothelial cells release adhesion molecules under the influence of cytokines. The connection becomes irreversible, and the cell flattens out.
- Diapedesis (penetration). The neutrophil extends a pseudopodium and squeezes through the vessel wall (typically paracellularly — between cells).
In tissues, the cell moves due to the reorganization of the actin cytoskeleton filaments. The direction of movement is guided by chemotaxis — a gradient of chemical signals emanating from the site of injury.
Bacterial destruction and pus formation
Neutrophils act as microphages. Target recognition is most efficient during opsonization — when a bacterium is "tagged" with IgG antibodies, whose $F_c$-fragment has corresponding receptors on the leukocyte.
The process of intracellular destruction proceeds as follows:
- A phagosome is formed containing the captured bacterium.
- The phagosome fuses with specific and later with azurophilic granules, forming a single phagolysosome.
- A "respiratory burst" occurs — a sharp production of reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical).
As a result of enzyme and reactive oxygen species attack, the bacterium dies and is hydrolyzed. During massive phagocytosis, many neutrophils die, releasing aggressive enzymes outward. From dead leukocytes, destroyed tissues and dead bacteria, pus forms at the site of inflammation.
Briefly: answers to topical questions
What receptors are present on the neutrophil plasmalemma for target recognition?
The neutrophil plasmalemma features a diverse receptor apparatus for interacting with targets, inflammatory mediators, and the endothelium. The main groups of receptors include:
- Fc receptors — recognize the Fc regions of immunoglobulins (FcγRII, FcγRIII) for phagocytosis of opsonized bacteria.
- Complement receptors — recognize complement components (CR1, CR3).
- Lipopolysaccharide receptors — CD14, working in conjunction with the TLR4 receptor.
- Bacterial wall receptors — bind directly to glycolipids and proteins.
- Damage-associated receptors — react with oligosaccharides of damaged self-cells.
- Adhesion molecules — β2-integrins (LFA-1, Mac-1).
- CD13 — aminopeptidase N, which serves as a receptor for a number of viruses.
What is the lifespan of neutrophils in the bloodstream and in tissues?
The total lifespan of a neutrophil after exiting the bone marrow is about 8 days, with the residence time in various body compartments strictly distributed.
| Compartment | Duration of stay |
|---|---|
| Bloodstream | 7–10 hours (less than 12 hours) |
| Tissues | 3–5 days |
After circulating in the blood, neutrophils migrate to tissues where they perform their main functions. Upon completion of their lifecycle in tissues, they undergo spontaneous apoptosis and are phagocytosed by resident macrophages to prevent damage to surrounding tissues.
To remember the main composition of primary (azurophilic) granules, use the phrase "My Cat Digests Every Lipid": Myeloperoxidase, Cationic proteins, Defensins, Elastase, Lysosomal enzymes.
Class and exam questions
Can mature neutrophils divide?
No. All forms circulating in the blood (including young and band forms) are terminally differentiated cells and lack mitotic activity.
How do neutrophils survive in a hypoxic focus of inflammation?
The energy metabolism of these cells relies entirely on anaerobic glycolysis. Their cytoplasm contains stores of their own substrate in the form of glycogen granules.
What is the difference between contact and distant bacterial killing?
Contact killing is classic phagocytosis resulting in phagolysosome formation. Distant killing ("exocytosis") involves the release of antibacterial substances from secondary and tertiary granules directly into the extracellular environment.
What else to study on this topic
- Biochemical mechanisms of antimicrobial action (role of lactoferrin, lysozyme, and alkaline phosphatase)
- Molecular basis of the respiratory burst in phagolysosomes
- Receptor apparatus of the granulocyte plasmalemma
- Mechanisms of target recognition: direct binding and opsonization
- Normal features of the white blood cell differential count
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