Granulocytes

Neutrophils: Initiators of Inflammation

Neutrophils form the basis of the leukocyte pool and are the first to arrive at the site of infection. They are "potential killers" whose main task is direct antimicrobial action (destroying bacteria, viruses, and fungi), as well as the elimination of damaged self-cells, such as epithelial cells.

Their granular apparatus is divided into two main types:

• Primary (azurophilic) granules: contain acid hydrolases.
• Secondary (specific) granules: include enzymes (lysozyme, lactoferrin, alkaline phosphatase).

Additionally, the granules contain antimicrobial peptides—α-defensins. Activation of these cells occurs under the influence of cytokines and immune complexes. Pathogen destruction is achieved via two pathways: phagocytosis (intracellular digestion) and degranulation (release of effector molecules and bactericidal substances into the extracellular space).

Receptor Apparatus and Chemotaxis

To recognize threats and mount a response, neutrophils utilize a rich repertoire of surface receptors:

• TLR (Toll-like receptors): recognize specific pathogen-associated molecular patterns.
• FcγR: bind targets opsonized with immunoglobulins G (IgG).
• CR1, CR2, CR4: interact with complement system components.
• Cytokine and chemokine receptors: ensure the accumulation of cells at the lesion site.

Neutrophil recruitment (chemotaxis) is driven by interleukin-8 (IL-8), tumor necrosis factor (TNF-α), interferon-gamma (IFN-γ), GM-CSF (GM-CSF), as well as complement anaphylatoxins C3a and C5a. Once on site, the mobilized cells themselves actively secrete antiviral cytokines, TNF-α, and defensins.

Tissue Migration Cascade (Extravasation)

The transition of granulocytes from the circulating blood into inflamed tissue is a strict multi-step process:

1. Rolling (Rolling): initial deceleration of movement. The cell "rolls" along the vascular endothelium via adhesion molecules called selectins.
2. Tethering (Tethering): formation of a tighter contact driven by the molecular interaction of L-selectin on the neutrophil surface with CD34 on the endothelium.
3. Adhesion (Adhesion): firm arrest of the cell. Neutrophils synthesize and express β2-integrins (e.g., LFA-1), which bind to endothelial cells.
4. Diapedesis (Diapedesis): transmigration of blood cells through the intact vascular wall.
5. Chemotaxis: directed movement within the tissue directly toward the inflammatory focus driven by a chemokine concentration gradient.

Eosinophils and Basophils

Eosinophils play a key role in anti-parasitic immunity (destruction of helminths) and participate in allergic reactions. Their secretory activity includes the release of:

• Lipid mediators: leukotrienes, thromboxane A2, platelet-activating factor (PAF).
• Reactive oxygen species (radicals).
• Toxic proteins: major basic protein (MBP) and eosinophil cationic protein (ECP). Clinically, it is important that these proteins are toxic to the bronchial epithelium and are involved in the pathogenesis of bronchial asthma.

Basophils are granulocytes circulating in the blood whose main functional role is to maintain chronic allergic inflammation. The mediators they release stimulate the secretion of platelet-activating factor and increase vascular wall permeability.

Class and exam questions

What else to study on this topic

• Molecular mechanisms of TLR, FcγR, and complement system receptors
• Biochemistry of degranulation: mechanism of action of acid hydrolases and lysozyme
• The role of lipid mediators (leukotrienes and thromboxane A2) in the allergic response
• Interaction of L-selectin and CD34 during neutrophil tethering to the endothelium
• Synthesis and functions of antimicrobial peptides (α-defensins)

Other topics in "Immunology"

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