Neutrophils: Initiators of Inflammation
Neutrophils form the backbone of the leukocyte pool and are the first to arrive at the site of infection. They are 'potential killers' whose primary task is direct antimicrobial action (destruction of bacteria, viruses, and fungi), as well as the elimination of damaged host 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 such as lysozyme, lactoferrin, and alkaline phosphatase.
Additionally, the granules contain antimicrobial peptides—α-defensins. Activation of these cells occurs via cytokines and immune complexes. Pathogen destruction is achieved through 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 array of surface receptors:
- TLR (Toll-like receptors): recognize specific pathogen-associated molecular patterns.
- FcγR: bind targets opsonized by immunoglobulins G (IgG).
- CR1, CR2, CR4: interact with complement system components.
- Cytokine and chemokine receptors: ensure cell accumulation at the lesion site.
Chemotaxis of neutrophils is driven by interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), GM-CSF (GM-CSF), and complement anaphylatoxins C3a and C5a. Once arrived, these mobilized cells 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:
- Rolling: initial deceleration of movement. The cell 'rolls' along the vascular endothelium via adhesion molecules called selectins.
- Tethering: formation of tighter contact due to molecular interaction between L-selectin on the neutrophil surface and CD34 on the endothelium.
- Adhesion: firm arrest of the cell. Neutrophils synthesize and express β2-integrins (e.g., LFA-1), which bind to endothelial cells.
- Diapedesis: transmigration of blood cells through the intact vessel wall.
- Chemotaxis: directed movement within the tissue directly toward the inflammatory focus along a chemokine concentration gradient.
Eosinophils and Basophils
Eosinophils play a key role in antiparasitic immunity (destruction of helminths) and participate in allergic reactions. Their secretory activity includes the release of:
- Lipid mediators: leukotrienes, thromboxane A2, and platelet-activating factor (PAF).
- Reactive oxygen species (radicals).
- Toxic proteins: major basic protein (MBP) and eosinophil cationic protein (ECP). Clinically, these proteins are toxic to bronchial epithelium and contribute to the pathogenesis of bronchial asthma.
Basophils are circulating blood granulocytes whose primary functional role is maintaining chronic allergic inflammation. The mediators they release stimulate the release of platelet-activating factor and increase vascular permeability.