Stages of allergic reaction development
The allergic response always goes through three consecutive phases:
- Immune phase. Begins upon initial exposure to the antigen. Immunocompetent cells recognize and interact with the allergen.
- Pathochemical phase. Synthesis and release of cytokines and specific allergy mediators are triggered. Effector cells are activated.
- Pathophysiological phase. Clinical manifestations of the reaction. They can affect the skin (itching, rash), blood vessels (edema), or the respiratory system (asthma attacks).
Most commonly, allergies occur via an IgE-dependent pathway, though other immune mechanisms are frequently involved as well.
Classification of hypersensitivity reactions
Historically, R. Cooke (1947) divided allergic reactions based on their onset speed into immediate hypersensitivity (IHS) and delayed hypersensitivity (DHS) types.
Later, in 1963, P. Gell and R. Coombs identified 4 main types of tissue damage in allergies. This scheme remains fundamental in modern immunology.
| Gell-Coombs type | Name | Participants | Clinical examples |
|---|---|---|---|
| Type I | Anaphylactic | IgE (less commonly IgG4) | Anaphylactic shock, pollinosis, urticaria, atopic asthma |
| Type II | Cytotoxic | IgG, IgM | Drug allergy, hemolytic anemia, leukopenia |
| Type III | Immune complex-mediated | IgG, IgM in complexes | Serum sickness, Arthus reaction, extrinsic allergic alveolitis |
| Type IV | Cell-mediated (delayed-type hypersensitivity) | Macrophages, $T_H1$ | Contact dermatitis, transplant rejection, infectious allergy |
Comparison of immediate and delayed hypersensitivity
Immediate hypersensitivity (IHS) is mediated by humoral immunity—IgE, IgG, and IgM antibodies (Types I, II, and III according to Gell and Coombs). The reaction develops rapidly: from several minutes to several hours after encountering the allergen. Vasodilation occurs, blood vessels become permeable, leading to itching, bronchospasm, and edema. In the late stages of IHS, products of eosinophils and neutrophils are recruited.
Delayed hypersensitivity (DHS) corresponds to Type IV according to Gell and Coombs and is mediated by cellular immunity. The antigen interacts directly with macrophages and Th1 lymphocytes, bypassing antibodies. The reaction develops 24–72 hours (1–3 days) after contact. Macrophages and T lymphocytes accumulate in the tissues, causing induration and local inflammation.
Etiology: Characteristics of allergens
Allergens are antigens (mostly of protein nature with a molecular weight of 10–80 kDa). Based on their route of entry into the body, they are conventionally divided into food, contact, parenteral (e.g., insect venom), and aerogenic (inhabited/inhaled).
Aeroallergens include fungal spores, animal dander, house dust mite particles (especially Pyroglyphidae, which are potent indoor allergens), and pollen.
Pollen allergens have distinct seasonality and geographic distribution: trees bloom in spring, grasses in summer, and weeds at the turn of summer and autumn. An important feature of pollen is its ability to cross-react due to the similarity of its antigens with components of certain foods. A separate group of potent chemical allergens consists of drugs that act as haptens.
Briefly: answers to topical questions
Which cells and immunoglobulins are involved in type I hypersensitivity reactions?
- Mast cells (mast cells) and basophils are the main effector cells, on the surface of which immunoglobulins are fixed.
- IgE (immunoglobulin E) and less commonly IgG4 are the main immunoreagents responsible for the development of an anaphylactic reaction.
- T-helper 2 cells (Th2) and antigen-presenting cells are involved in the immunological phase and the production of specific antibodies.
Specifically, which mediators are released during the pathochemical phase of a type I allergic reaction?
- Histamine is a vasoactive amine released from mast cell and basophil granules.
- Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are lipid mediators that constitute the "slow-reacting substance of anaphylaxis".
- Prostaglandin D2 (PgD2) and platelet-activating factor (PAF) are mediators involved in bronchoconstriction and increased vascular permeability.
- Heparin is a proteoglycan stored in mast cell granules.
What is the mechanism of target cell destruction in cytotoxic (type II) hypersensitivity?
- Interaction of antibodies of the IgG and IgM classes with antigens that are components of the cell membrane or attached haptens.
- Activation of effector mechanisms (complement system or killer cells) as a result of the formation of the cell-antigen-antibody complex.
- Cytolysis is the direct destruction of target cells under the action of triggered immune mechanisms.
What are haptens and why are they capable of causing allergies?
- Haptens (incomplete antigens) are low-molecular-weight compounds (less than 10 kDa) that are unable to induce an immune response on their own.
- Acquisition of immunogenicity — haptens become complete antigens after binding to the body's carrier proteins.
- Upon binding to a carrier protein, the hapten acquires the ability to induce an immune response and can participate in the development of an allergic reaction.
What is the role of eosinophils in the late stages of immediate-type hypersensitivity?
- Recruitment to the focus — eosinophils are attracted by chemotactic factors and Th2 cytokines in the late phase of inflammation.
- Secretion of toxic proteins — they release major basic protein (MBP), eosinophil cationic protein (ECP), peroxidase, and leukotrienes.
- Tissue damage — these products cause direct damage and cytotoxicity to the airway epithelium, sustaining inflammation.
Class and exam questions
Which antibodies are involved in Type II and Type III reactions?
In both cases, IgG and IgM immunoglobulins play a key role. The difference is that in type III, they operate as part of circulating immune complexes.
What is the clinical onset time for delayed-type hypersensitivity?
Symptoms of delayed-type hypersensitivity (type IV) develop within 24 to 72 hours (1–3 days) after re-exposure to the allergen.
What is the role of T-lymphocytes in allergy?
Type 1 T-helper cells ($T_H1$) and macrophages are the main participants in delayed-type hypersensitivity (type IV), providing a cell-mediated response and tissue infiltration.
What else to study on this topic
- Pathogenesis of anaphylactic shock
- Mechanisms of immune complex formation (Type III)
- Haptens: mechanism of drug conversion into full-fledged allergens
- Features of cross-reactivity between pollen and food
- Arthus phenomenon and serum sickness
- Mechanisms of anti-receptor reactions within the cytotoxic type
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