Gell and Coombs classification
Since 1969, medicine has used the classification of hypersensitivity reactions (P. Gell, R. Coombs), which divides them into four main types:
- Type I (immediate). Develops upon the interaction of an allergen with IgE antibodies fixed on mast cells. This leads to massive degranulation and release of mediators.
- Type II (cytotoxic). Antibodies (IgG1, IgG3) bind to antigens directly on the surface of the body's cells, triggering the destruction of target cells involving complement and killer cells.
- Type III (immune complex). Antibodies (usually IgG) bind soluble extracellular antigens. The resulting complexes deposit in tissues, activating the complement system and recruiting neutrophils, which causes inflammation.
- Type IV (delayed-type). Unlike the first three, this is a cell-mediated immune response. The antigen is recognized by the T-cell receptor (TCR). Sensitized Th1 lymphocytes release cytokines and activate macrophages.
Mechanisms of type I allergy (immediate)
Type I allergy occurs as a pathological response to allergens — substances that stimulate the production of IgE. The entire process is divided into two main phases:
- Sensitization phase. Upon the first contact with an allergen, a humoral immune response is triggered: IgE antibodies are synthesized. They attach to specific high-affinity FcεRI receptors on the surface of mast cells. There are no external clinical symptoms at this stage.
- Effector phase. Upon re-exposure, the allergen (or a similar cross-reacting one) binds to the pre-existing IgE on mast cells. A lightning-fast reaction occurs (within minutes) — degranulation.
The development of the response itself is divided into immunological (recognition) and pathochemical (mediator release) stages.
Manifestations and consequences of allergic reaction
The release of mediators (histamine, eicosanoids, kinins) in type I allergy causes a number of characteristic local effects:
- Vasodilation and increased vascular permeability. Histamine and leukotrienes cause the endothelium to contract. The result is redness, fluid and blood cells leaking into tissues, and the formation of edema, rashes, and wheals.
- Smooth muscle spasm. Leukotrienes and prostaglandin D2 cause severe contraction of muscles, primarily the bronchi, which manifests as an asthma attack.
- Secretion and irritation. Leukotrienes stimulate mucus production, while histamine and thromboxane A2 irritate nerves, causing itching and pain.
Late phase and chronic progression The early reaction is followed by a late phase driven by eosinophils, basophils, and neutrophils. They migrate to the lesion under the influence of cytokines from mast cells and Th2 lymphocytes, forming persistent allergic inflammation (edema, tissue induration). In a chronic course, cytokines (e.g., IL-13) lead to tissue remodeling: the epithelium atrophies, and the muscle layer proliferates, impairing organ function.
Briefly: answers to topical questions
What diseases are classic clinical examples of type III (immune complex) hypersensitivity?
Classic clinical examples of type III (immune complex) hypersensitivity are diseases caused by the pro-inflammatory effect of soluble immune complexes. Such pathologies include:
- Immune complex glomerulonephritis
- Systemic lupus erythematosus
- Polyarteritis nodosa
- Serum sickness
- Exogenous allergic alveolitis
- Arthus reaction
What three classic stages (according to Ado) are distinguished in the pathogenesis of allergic reactions?
Three consecutive stages of process development are distinguished in the pathogenesis of allergic reactions. These include:
- Immunological stage (or immunogenic) — the phase of immune reactions including sensitization and the interaction of the allergen with antibodies or receptors.
- Pathochemical stage (or pathobiochemical) — the phase of biochemical reactions accompanied by cell degranulation and the release of allergy mediators.
- Pathophysiological stage (stage of clinical manifestations) — the response of surrounding tissue cells to the action of mediators, determining the external symptoms of allergy.
Which mast cell mediators are preformed (primary) and which are newly synthesized (secondary)?
Mast cell mediators are divided into two groups.
| Mediator group | Representatives |
|---|---|
| Preformed (primary) | Histamine, heparin, serotonin, tryptase, chymase, peroxidase, RNase, chondroitin sulfates A and C, eosinophil and neutrophil chemotactic factors |
| Newly synthesized | Eicosanoids, including leukotrienes |
Preformed mediators are stored in mast cell granules and released upon degranulation. Eicosanoids are synthesized after cell activation. PAF and TNF-α are indicated in sources as late-phase mediators, but their classification as newly synthesized mediators is not explicitly stated in the cited sources.
What specific mechanisms of cytotoxicity lead to the destruction of target cells in type II hypersensitivity?
The destruction of target cells in type II (cytotoxic) hypersensitivity occurs through several mechanisms of immune cytolysis. The main effector mechanisms include:
- Complement-dependent cytolysis — activation of the complement system by antibodies (IgG, IgM), leading to lysis of the membranes of blood formed elements and other cells.
- Antibody-dependent cellular cytotoxicity (ADCC) — destruction of target cells involving killer cells that interact with antibodies via Fc receptors.
- Cellular contact-dependent cytolysis — a variant of immune cytolysis carried out by effector cells.
The four types of hypersensitivity can be remembered using the word ACID: A — Anaphylactic (I), C — Cytotoxic (II), I — Immune complex (III), D — Delayed (IV).
Class and exam questions
How does type III differ from type II hypersensitivity?
In type II, antibodies attack antigens fixed on the surface of the body's own cells. In type III, antibodies bind free-floating antigens, forming complexes that subsequently deposit in tissues and blood vessels.
What happens during the sensitization phase?
The body encounters the allergen for the first time, produces IgE antibodies against it, which settle on mast cells. There are no clinical symptoms of allergy in this phase.
What else to study on this topic
- Detailed pathogenesis of anaphylactic shock
- The role of eicosanoids (LTC4, LTD4) in bronchospasm
- Mechanisms of airway remodeling in chronic asthma
- Cytokine profile of the Th2 response and IL-13
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