Stages of allergic reaction development
The entire pathological response process can be divided into two key stages.
1. Sensitization stage (initial antigen entry) Antigen-presenting cells (APCs) capture the allergen and present it to type 2 T-helper cells (Th2). With the participation of cytokines (IL-4 and IL-13), B lymphocytes are activated, transforming into plasma cells that actively synthesize specific IgE. These antibodies attach via their Fc fragment to high-affinity receptors (FcεRI) on the surface of mast cells and basophils. The body becomes "primed", but there are no symptoms yet.
2. Pathochemical and pathophysiological stages (re-exposure) Upon re-exposure, the allergen binds adjacent IgE molecules on the membrane of sensitized cells (cross-linking occurs). This triggers a massive influx of calcium ions into the cell. Degranulation is initiated: preformed substances (such as histamine) are instantly released from granules, and the synthesis of new lipid mediators (leukotrienes) and cytokines begins. Classical pharmacological effects occur: action on the vascular bed, nerve endings, and respiratory tract.
Key mediators and maintenance of inflammation
Effector cells release a vast spectrum of biologically active substances that determine the severity of the condition:
- Vasoactive amines and proteoglycans: histamine and heparin.
- Lipid mediators: prostaglandins, leukotrienes, and platelet-activating factor (PAF).
- Enzymes: tryptase, chymase.
- Cytokines: IL-3, IL-4, IL-5, TNF-$\alpha$, and others.
Interesting fact: in addition to the classical IgE pathway, basophils have Fc receptors for IgG. When immune complexes bind to these receptors, basophils secrete platelet-activating factor. Its ability to increase vascular permeability is 10,000 times higher than that of histamine. Activated platelets, in turn, release serotonin, which helps maintain chronic allergic inflammation.
Late phase and the role of eosinophils
Over time, new cells (macrophages, neutrophils) are recruited to the inflammation site, but eosinophils play a special role. Mast cells release specific eosinophil chemotactic factors (ECF), forcing eosinophils to migrate into tissues.
At the site, eosinophils begin to secrete aggressive substances: cationic proteins, enzymes, and leukotrienes. One of the most important is major basic protein, which causes direct epithelial damage, exacerbating tissue destruction in allergies.
Clinical forms and diagnostic principles
The presence of a hereditary predisposition to immediate-type hypersensitivity (genetic hyperproduction of IgE, barrier permeability) is called atopy.
Manifestations of type I reactions are divided into:
- Systemic: anaphylactic shock. Develops fulminantly, accompanied by a sharp drop in blood pressure (collapse), bronchospasm, and carries a high risk of death. Frequent triggers include parenteral drugs and insect venom.
- Local: allergic urticaria, angioedema (Quincke's edema), allergic rhinitis, pollinosis (hay fever), atopic bronchial asthma, food allergy.
Diagnostics includes the determination of total and specific IgE in blood serum, cell activation markers (histamine, tryptase levels). Eosinophilia is detected in smears (e.g., nasal) and blood. In vivo provocative tests (skin, nasal) are used for confirmation.
Aetiopathogenetic treatment includes allergen-specific immunotherapy (ASIT) — the administration of increasing doses of the allergen to achieve organism hyposensitization.
Briefly: answers to topical questions
What is the exact immunological mechanism of hyposensitization during allergen-specific immunotherapy (ASIT)?
The exact immunological mechanism of hyposensitization during allergen-specific immunotherapy (ASIT) lies in the induction of immune tolerance.
The patient is administered chronically increasing doses of the causative allergen. This leads to the following effects:
- "Retraining" of the immune system.
- Reduced sensitivity to the trigger.
- Elimination of symptoms upon natural contact with the allergen.
What specific types of IgG Fc receptors are expressed on the basophil membrane?
Fc receptors for class G immunoglobulins (IgG) are expressed on the basophil membrane, although their specific types are not specified.
Binding of IgG within immune complexes to these receptors leads to the following effects:
- Secretion of platelet-activating factor.
- Platelet activation.
- Increased vascular permeability (10,000 times stronger than histamine).
This contributes to the maintenance of chronic allergy.
Which intracellular kinases and adapter proteins provide signal transduction for degranulation following IgE cross-linking?
Signal transduction for degranulation following IgE cross-linking is provided by tyrosine kinase Syk and protein kinase C (PKC). Adapter proteins in this cascade are not specified.
The process includes the following stages:
- Tyrosine kinase (Syk) is activated after phosphorylation of ITAM motifs of the receptor $\gamma$-chain and triggers phospholipase C (PLC$\gamma$).
- Protein kinase C (PKC) is activated by diacylglycerol and calcium ions, after which it phosphorylates the myosin light chain.
This leads to a reaction of cytoskeletal elements and exocytosis of mediators.
Which specific interleukins and chemokines function as eosinophil chemotactic factors (ECF)?
In the cited sources, the specific list of interleukins and chemokines that are eosinophil chemotactic factors (ECF) is not specified. It is indicated that mast cells release eosinophil chemotactic factors that attract eosinophils to the reaction site. Leukotriene B4 and platelet-activating factor are named agents providing bronchial eosinophilic infiltration, and eosinophil chemotactic factor A is indicated among acidic lipid derivatives.
Class and exam questions
What is the role of IgG in type I reactions?
Basophils express IgG receptors. Binding of immune complexes to these receptors causes the secretion of a potent platelet-activating factor, which maintains chronic allergic inflammation.
What is atopy?
This is a genetic predisposition to the development of immediate-type hypersensitivity, which is characterized by excessive IgE production and increased permeability of tissue barriers.
How do eosinophils work in the late phase of the reaction?
They are attracted to the focus by mast cell chemotactic factors and release aggressive enzymes, leukotrienes, and major basic protein, which directly damages the epithelium.
What else to study on this topic
- Mechanism of B-lymphocyte activation with the participation of interleukins 4 and 13
- Pharmacological effects of platelet-activating factor (PAF) and serotonin
- Pathogenesis and main triggers of anaphylactic shock
- Differences between allergic urticaria and angioedema
- Methodology and interpretation of skin provocation tests
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