Components of the innate immune response
Innate protective reactions are provided by several functional groups of cells. The main effectors include monocytes, macrophages, dendritic cells, and granulocytes (neutrophils, eosinophils, basophils), as well as mast cells.
In addition, lymphoid elements play an important role, such as natural killer cells (NK cells), NKT cells, B1 and T$\gamma\delta$ lymphocytes. A direct mechanical and chemical barrier is formed by auxiliary cells: epithelial cells of the skin and mucous membranes, vascular endothelial cells, keratinocytes, and platelets.
Characteristics and functions of phagocytes
The phagocyte system is formed primarily by monocytes, macrophages, and neutrophils. Their main task is to identify 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 target.
- Bactericidal activity — destruction of engulfed microorganisms through the synthesis of nitric oxide (NO) and the generation of peroxide radicals (the so-called respiratory burst).
- Secretory activity — production of cytokines, antimicrobial peptides, and complement components.
- Chemotaxis — directed cell movement to the epicenter of inflammation.
- Antigen presentation — processing of foreign material and its presentation to T lymphocytes to initiate adaptive immunity.
Tissue differentiation of macrophages
The mononuclear phagocyte system (MPS) is 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 site, they acquire specific names and properties:
| Tissue / Organ | Macrophage name |
|---|---|
| Connective tissue | Histiocytes |
| Liver | Kupffer cells (stellate cells) |
| Bone tissue | Osteoclasts |
| Central nervous system | Microglia |
| Joints | Synovial cells (type A) |
| Serous cavities and lungs | Alveolar, pleural, peritoneal |
Receptors and activation
For efficient target searching, macrophages are equipped with a variety of receptors. Scavenger receptors and mannose receptors bind components of microbial walls and damaged tissues. Receptors of the Toll-like receptor (TLR) family transmit intracellular signals for the production of effector molecules, while integrins ensure tight contact with other cells.
Upon macrophage activation, a respiratory burst occurs — an intensive 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 enhanced.
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 (classical activation). Induced by interferon-gamma and tumor necrosis factor (TNF-$\alpha$). They produce pro-inflammatory cytokines (IL-1, IL-6, IL-12), reactive oxygen and nitrogen species. They are responsible for sustaining inflammation and cytotoxicity. When overactive, they can cause damage to host tissues.
- 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 activity of the M2 pathway can lead to immunosuppression.
Briefly: answers to topical questions
What stages does the process of phagocytosis sequentially include?
The process of phagocytosis traditionally includes 8 sequential stages, or alternatively, 4 main stages are distinguished.
The expanded classification includes:
- Chemotaxis — directed movement of the phagocyte toward the target.
- Adhesion — establishing physical contact and sticking.
- Membrane activation — preparation for engulfment.
- Immersion — wrapping around the object.
- Phagosome formation — closure of the membrane.
- Phagolysosome fusion — fusion of the phagosome and lysosome.
- Killing and degradation — intracellular digestion.
- Release of degradation products — removal of residues.
The simplified classification distinguishes approach, recognition with adhesion, engulfment, and destruction.
Which enzymes ensure the development of the respiratory burst in phagocytes?
The development of the respiratory burst in phagocytes is provided by enzymes that generate reactive oxygen species.
- NADPH oxidase — catalyzes the reaction of superoxide anion formation from oxygen and the oxidized form of the NADPH cofactor.
- Superoxide dismutase — ensures the formation of hydrogen peroxide from two molecules of superoxide anion.
These enzymes trigger a chain of reactions leading to the formation of highly reactive free radicals and oxygen ions with pronounced bactericidal activity to destroy phagocytized microorganisms.
What is incomplete phagocytosis and for which infections is it characteristic?
Incomplete phagocytosis is a phenomenon in which engulfed microorganisms are not destroyed by lysosomal enzymes, but survive inside the phagocyte.
This phenomenon is indicated in sources for the following infections and conditions:
- Leishmaniasis — the pathogen survives inside the phagocyte.
- Meningococcal infection — during intense bacteremia, neutrophils deplete their myeloperoxidase resource, phagocytosis becomes incomplete, and neutrophils containing viable meningococci inside become a transport system for the pathogen.
- Gonorrhea (Neisseria gonorrhoeae) — gonococci are located inside leukocytes; Por proteins prevent the fusion of the lysosome with the phagosome and ensure the survival of gonococci inside phagocytes.
- Chlamydia — among the reasons for treatment difficulties and failures, immunological features including incomplete phagocytosis are noted.
- Septicemia — incomplete phagocytosis is observed in neutrophilic leukocytes, with endocytobiosis predominating.
- Tuberculosis / mycobacterial infections — mycobacteria survive inside macrophages and prevent the fusion of the phagosome with the lysosome.
To remember polarization: M1 — "Swords" (attack, classical inflammation), M2 — "Trowel" (repair tissues, alternative activation).
Class and exam questions
How do monocytes differ from tissue macrophages?
Monocytes are immature circulating cells located in the bloodstream. Upon migration into tissues, they differentiate into resident tissue macrophages with a more pronounced capacity for phagocytosis and secretion.
Which cells belong to polymorphonuclear leukocytes?
This is a synonym for neutrophils — cells that are predominantly found in the blood and are among the first to migrate to the site of infection under the influence of chemokines to carry out phagocytosis.
What is the essence of the respiratory burst?
This is a sharp increase in the production of reactive oxygen species (such as hydrogen peroxide and superoxide anion) inside an activated phagocyte, which is necessary for the chemical digestion of the captured microbe.
What else to study on this topic
- Mechanisms of antigen processing and presentation by dendritic cells.
- Cytokine profile: the detailed role of TNF-α and IL-12 in the immune response.
- Features of anti-parasitic immunity (the role of eosinophils, mast cells, and basophils).
- Mechanism of action of natural killer (NK) cells in the lysis of tumor cells.
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