Allergen-specific immunotherapy

Principles and mechanism of action

Allergen-specific immunotherapy is based on the phenomenon of desensitization. A patient who is already sensitized to a specific substance is repeatedly administered this allergen (most often subcutaneously). The dose of the allergen is gradually increased with each administration.

The exact mechanisms through which the clinical effect is achieved are not fully understood. However, several well-founded theories exist:

• Activation of regulatory T cells — considered the most likely mechanism. These cells suppress the excessive immune response to allergens, regulating both Th1 and Th2 pathways.
• Immune response deviation — shifting the balance from the allergic Th2 type to the Th1 type.

The efficacy of the method is confirmed by an increase in the number and activity of natural regulatory T cells (e.g., in allergies to pollen, mites, or cow's milk).

Criteria of efficacy

The success of the administered immunotherapy is evaluated by a number of clinical, laboratory, and tissue parameters.

Clinical signs:

• Allergy symptoms disappear or significantly diminish.
• The season-specific peak in allergen-specific IgE production is absent.

Immunological changes:

• Reactivity in skin prick tests and other assays decreases.
• The serum titer of specific IgG, which act as "blocking" antibodies, increases.
• The concentration of specific IgA and IgG increases in saliva.
• The concentration of allergen-specific IgE increases initially (the first few months) and then steadily decreases.

Cellular-level alterations:

• The number of mast cells in tissues decreases.
• The level of Th2 cytokines (in blood and tissues) and Th1 cytokines (in blood) decreases.
• The level of IL-10 and the number of regulatory T cells increase.
• The ability of T cells to undergo allergen-specific proliferation in vitro decreases.

Clinical significance and complications

The main advantage of AIT is providing a long-term clinical effect and halting the progression of the allergic process. The method does not achieve a hundred-percent cure (repeated courses are often required), but it:

• prevents the appearance of allergies to new substances (expansion of the allergen spectrum);
• significantly reduces the dosages of anti-allergic medications taken.

Despite its high efficacy, AIT is associated with risks. The main complication is severe systemic reactions, up to and including fatal anaphylactic shock. As a rule, such situations arise due to gross violations of the allergen administration schedule.

Biotherapy and promising developments

To improve the efficacy of AIT, allergovaccines are being developed. In these, the allergen is modified or combined with immunomodulators to stimulate a shift toward a Th1 response or additionally activate regulatory T cells.

In addition, biotherapy aimed at inactivating effector molecules is actively developing:

• Anti-TNFα antibodies suppress inflammation and currently demonstrate the best clinical results.
• Anti-IgE antibodies and monoclonal antibodies against IgE receptors (FcεRI) lower free IgE levels and block mast cell activity (currently in clinical trials).
• Monoclonal antibodies against IL-5, its receptor, or CCR3 are aimed at suppressing eosinophils.
• Drugs targeting IL-4 and IL-13 proved to be less effective than expected.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Pharmacotherapy of allergies: antihistamines of various generations
• Drugs for relieving bronchospasm: β2-adrenergic agonists and methylxanthines
• Anti-inflammatory therapy for allergies: glucocorticoids and leukotriene receptor antagonists
• Cytotoxic hypersensitivity type (Type II) and its effector mechanisms
• Types of immune cytolysis: cell-contact and antibody-mediated

Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"

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