Pathogen structure as an immune target
The logic of the antifungal response is always based on the structure of the pathogen itself. Fungi differ fundamentally from bacteria by having a thick, complex, multilayered cell wall.
This exact structure becomes the main target for recognition by the host's defense systems. The cell wall includes:
- Polysaccharides: mannans, glucans, cellulose, and chitin (the primary structural framework).
- Proteins and lipids embedded in the polysaccharide matrix.
Innate immunity: first line of defense
Innate immunity takes the primary hit upon contact with fungal agents. Defense at this stage is implemented through three main mechanisms:
- Barrier factors. The physical integrity of the skin and mucous membranes prevents invasion. Additionally, sebaceous and sweat gland secretions contain natural antimicrobial peptides that are detrimental to micromycetes.
- Competitive defense. Healthy normal microflora acts as a potent antagonist. Bacteria compete with fungi for nutrients and ecological niches, strictly holding back their excessive growth.
- Receptor recognition. If a fungus breaches the barriers, innate immune cells come into play. They use specialized receptors (primarily TLR2, TLR4, and dectin-1) to "recognize" the polysaccharides of the fungal wall and trigger the inflammatory cascade.
Adaptive immunity and tissue reactions
If innate mechanisms fail, adaptive immunity is activated. In mycoses, T-cell immunity plays the leading role. The humoral response (production of IgM and IgG class antibodies) is of secondary importance and cannot independently ensure the complete clearance of fungi from the body.
A characteristic pathomorphological picture unfolds at the site of inflammation:
- Phagocytosis is sharply enhanced and activated.
- Specific epithelioid granulomas form, limiting the spread of the pathogen.
- Thrombosis frequently develops in blood vessels adjacent to the site of inflammation, which impairs tissue trophism but isolates the pathogen.
Clinical and immunological features of mycoses
Fungal infections (especially opportunistic ones) rarely affect completely healthy individuals. They manifest against the background of immunodeficiencies or after prolonged antibiotic therapy, when the controlling normal microflora is eradicated.
The infectious process is always accompanied by the development of delayed-type hypersensitivity (DTH). However, fungi are also capable of causing allergic reactions (immediate-type hypersensitivity — ITH).
Respiratory sensitization most commonly occurs upon inhaling microscopic fragments of fungi of the genera Aspergillus, Penicillium, Mucor, or Fusarium. The body begins synthesizing specific IgE antibodies, leading to the development of severe allergic diseases (e.g., bronchial asthma).
To diagnose a current infection (DTH) or allergy (ITH) in clinical practice, specific skin tests with fungal antigens are widely used.
Briefly: answers to topical questions
Which cells perform phagocytosis during fungal infections?
Phagocytosis in fungal infections is carried out predominantly by macrophages and neutrophils.
- Macrophages recognize fungi via lectin receptors (mannose receptor, DC-SIGN, dectin-1) and engulf them (e.g., alveolar macrophages phagocytose spores in coccidioidomycosis).
- Neutrophils provide phagocytosis and intracellular digestion of pathogens (e.g., in sporotrichosis).
- Monocytes also express receptors for pathogen recognition and endocytosis.
Which cytokines are released upon activation of T-cell antifungal immunity?
During the activation of T-cell antifungal immunity, interferon-gamma ($\gamma$-IFN) is released. During the immune response, T lymphocytes recognize fungal cell wall antigens and specific heat shock proteins, after which they secrete this cytokine. The release of interferon-gamma ensures macrophage activation, which subsequently leads to the efficient intracellular destruction of engulfed fungi.
What immune evasion mechanisms do pathogenic fungi use?
Pathogenic fungi use several mechanisms to evade the immune response and destruction by phagocytes.
- Blocking the fusion of phagocytic vacuoles and lysosomes — this mechanism has been described for the causative agent of coccidioidomycosis.
- Intracellular survival — Histoplasma species are facultative intracellular parasites, are engulfed by macrophages, multiply within phagolysosomes, and cause subsequent destruction of the macrophages.
- Capsule formation — in Cryptococcus species, the capsule inhibits phagocytosis.
Class and exam questions
Why do candidiasis and other mycoses often occur after a course of antibiotics?
Antibiotics destroy the normal bacterial microflora, which normally competes with fungi for nutrients. Deprived of competitors, fungi begin to multiply uncontrollably.
Which arm of immunity is more important for fighting fungi: cellular or humoral?
T-cell immunity plays the leading role. Humoral immunity (IgM, IgG antibodies) is of secondary importance in mycoses.
Through which receptors does the body recognize fungi?
The main "recognizers" of thick fungal cell wall components are innate immune receptors: TLR2, TLR4, and dectin-1.
Which fungi most frequently cause respiratory tract allergies?
Respiratory sensitization with IgE production is most frequently caused by mold fragments of the genera Aspergillus, Penicillium, Mucor, and Fusarium.
What else to study on this topic
- Structure of the fungal cell wall: chitin, glucans, and mannans
- Mechanism of epithelioid cell granuloma formation
- Opportunistic mycoses in the setting of HIV infection
- Dectin-1 receptor: structure and functions in the immune response
- Differences between DTH (infection) and ITH (allergy) in mycoses
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