Participants in the Innate Immune Response
Innate defense reactions are carried out by several functional groups of cells. Primary effectors include monocytes, macrophages, dendritic cells, and granulocytes (neutrophils, eosinophils, basophils), as well as mast cells.
Additionally, lymphoid elements play a crucial role, such as natural killer (NK) cells, NKT cells, B-1 cells, and $\gamma\delta$ T cells. Direct mechanical and chemical barriers are formed by auxiliary cells: epithelial cells of the skin and mucous membranes, vascular endothelial cells, keratinocytes, and platelets.
Characteristics and Functions of Phagocytes
The phagocytic system is primarily formed by monocytes, macrophages, and neutrophils. Their main task is to detect pathogens and damaged somatic cells using surface receptors, followed by engulfment (phagocytosis) and destruction of the target.
The functional profile of macrophages includes:
- Phagocytosis — direct engulfment and digestion of the object.
- Bactericidal activity — destruction of ingested microorganisms via the synthesis of nitric oxide (NO) and the generation of peroxide radicals (the respiratory burst).
- Secretory activity — production of cytokines, antimicrobial peptides, and complement components.
- Chemotaxis — directed movement of cells toward the epicenter of inflammation.
- Antigen presentation — processing foreign material and presenting it to T lymphocytes to initiate adaptive immunity.
Tissue Differentiation of Macrophages
The mononuclear phagocyte system (MPS) constitutes a unified cellular network. Its precursors are circulating blood monocytes. Upon leaving the vascular bed and entering organs, monocytes transform into tissue macrophages.
Depending on their localization, they acquire specific names and properties:
| Tissue / Organ | Macrophage Name |
|---|---|
| Connective tissue | Histiocytes |
| Liver | Kupffer cells (stellate macrophages) |
| Bone tissue | Osteoclasts |
| Central nervous system | Microglia |
| Joints | Synovial cells (type A) |
| Serous cavities and lungs | Alveolar, pleural, peritoneal macrophages |
Receptors and Activation
To effectively search for targets, macrophages are equipped with diverse receptors. Scavenger receptors and mannose receptors bind components of microbial cell walls and damaged tissues. Toll-like receptors (TLRs) transmit signals inside the cell to induce the production of effector molecules, while integrins ensure tight cell-to-cell contact.
Upon macrophage activation, a "respiratory burst" occurs—an intense production of reactive oxygen species (hydrogen peroxide, superoxide anion, hydroxyl radical, hypochlorite, singlet oxygen). Simultaneously, nitric oxide is generated, intracellular enzyme activity changes, and phagocytosis and cytokine secretion are drastically upregulated.
Macrophage Polarization (M1 / M2 Balance)
Macrophages exhibit high plasticity and can alter their phenotype under the influence of the microenvironment. Two main functional states are distinguished:
- M1 macrophages (classic activation). Induced by interferon-gamma and tumor necrosis factor alpha (TNF-$\alpha$). They produce pro-inflammatory cytokines (IL-1, IL-6, IL-12), reactive oxygen species, and reactive nitrogen species. They promote inflammation and cytotoxicity. When excessively active, they can cause host tissue damage.
- M2 macrophages (alternative activation). Formed under the influence of IL-4, IL-10, and transforming growth factor beta (TGF-$\beta$). Their main role is to suppress the inflammatory response, stimulate tissue regeneration, and produce anti-inflammatory molecules. Excessive M2 activity can lead to immunosuppression.