Characteristics of immunoglobulin D (IgD)
Immunoglobulin D is represented in the body as a monomer, which means it has two antigen-binding sites. Its concentration in blood serum is extremely low, accounting for less than 0.1% of the total antibody pool.
The primary localization of this class of immunoglobulins is the surface of B lymphocytes. There it exists in a membrane-bound form (mIg), often located together with immunoglobulin M (IgM). The main physiological function of IgD is the strict regulation of the B-cell life cycle: it is responsible for both their activation and the suppression of the immune response.
Functions and structure of immunoglobulin E (IgE)
Like IgD, immunoglobulin E is a monomer with two antigen-binding sites. Normally, it is contained in the blood in trace amounts — less than 0.01%.
In the body, IgE performs two fundamentally different, but equally important tasks:
- Anti-parasitic immunity. This is the primary protective function of this class of antibodies acquired during evolution.
- Allergic reactions. Participation in type I hypersensitivity reactions (anaphylaxis). This occurs because the Fc fragment of the IgE molecule is able to bind tightly to specific receptors on the surface of mast cells and basophils.
Sensitization: the immunological stage of allergy
The development of an immediate-type hypersensitivity (ITH) reaction begins with the initial contact of the body with an allergen. This process goes through several consecutive stages:
- Antigen capture. The initial entry of the allergen leads to its capture by specialized antigen-presenting cells — dendritic cells.
- Migration and presentation. Dendritic cells migrate to the lymph nodes. There they present allergen peptides in a complex with class II major histocompatibility complex (MHC II) to naive T-helper cells ($T_H0$).
- Differentiation. Under the influence of received signals, naive $T_H0$ differentiate into $T_H2$.
- B-cell activation. Specific $T_H2$ interact with B lymphocytes, which triggers the transformation of B cells into plasma cells.
- Antibody synthesis. The resulting plasmacytes begin to actively produce specific antibodies — IgE and IgG4.
Regulation of synthesis and fixation of IgE
The production process of immunoglobulin E is under the strict control of the cytokine system. Cytokines secreted by $T_H2$ cells (specifically, IL-4, IL-10, and IL-13) have a stimulating effect on IgE production. In contrast, cytokines of $T_H1$ cells (such as IFN-$\gamma$ and IL-2) inhibit and suppress the synthesis of this class of antibodies.
Synthesized IgE molecules do not remain free-floating. With their Fc fragment, they attach to high-affinity receptors called $Fc\epsilon R1$.
These receptors are localized on the surface of two cell types:
- Basophils, circulating in the bloodstream.
- Mast cells, which are numerous in mucous membranes and connective tissue.
Effector phase (pathochemical stage)
When a sensitized organism re-encounters the same allergen, the pathochemical stage is triggered, leading to visible manifestations of allergy:
- Binding. The re-entering allergen binds to IgE molecules that are already fixed on the surface of target cells.
- Cross-linking. The formation of «IgE–allergen» immune complexes leads to the so-called cross-linking of $Fc\epsilon R1$ receptors with each other.
- Cell activation. Receptor cross-linking opens ion channels, resulting in a massive influx of calcium ions ($Ca^{2+}$) into the cell.
- Degranulation. An increase in the intracellular calcium concentration causes a sharp release of granule contents (degranulation) from mast cells and basophils into the extracellular space, which determines the clinical picture of anaphylaxis.
Briefly: answers to topical questions
Which mediators are released during the degranulation of mast cells and basophils?
During the degranulation of mast cells and basophils, allergic reaction mediators are released.
- Preformed mediators from granules: histamine; serotonin, heparin, tryptase, chymase and other enzymes are also indicated for mast cells.
- Lipid mediators synthesized upon activation: leukotrienes, prostaglandin D2, platelet-activating factor.
- Cytokines: IL-5, IL-6, TNF-α, GM-CSF; a wide range of interleukins and TNFα is also described for mast cells.
These mediators participate in inflammatory and allergic reactions, including increasing vascular permeability, affecting the airways, and contracting smooth muscle.
Which types of heavy chains are part of immunoglobulin D and E molecules?
Immunoglobulin D and E molecules contain delta and epsilon type heavy chains, respectively.
- Immunoglobulin D (IgD) contains heavy δ-chains; they contain one variable and three constant domains.
- Immunoglobulin E (IgE) contains heavy ε-chains; they contain one variable and four constant domains.
The type of heavy chain determines the class, or isotype, of the immunoglobulin.
Against which specific classes of parasites is the protective action of immunoglobulin E directed?
The protective action of immunoglobulin E (IgE) is directed primarily against extracellular parasites, first and foremost helminths and their larvae.
The main battle takes place in the intestine, where more than 99% of IgE is secreted. Defense mechanisms include:
- Contact lysis — eosinophils interact with the helminth via the Fc fragment of IgE antibodies coating the parasite and release toxic granules.
- Mechanical removal — mast cells bind to IgE and release histamine, causing muscle spasms and the expulsion of intestinal helminths.
To avoid confusing cytokines: TH2 (IL-4, 10, 13) act as allergy «provocateurs» by stimulating IgE, while TH1 (IFN-γ, IL-2) act as «brakes» suppressing its production.
Class and exam questions
What is the main normal protective role of immunoglobulin E?
Normally, in addition to participating in pathological allergic reactions, the main protective function of IgE is to provide reliable anti-parasitic immunity.
What triggers the degranulation of mast cells?
The process is triggered upon re-contact with the allergen, when cross-linking of FcεR1 receptors occurs. This leads to the entry of calcium ions into the cell and the subsequent release of granule contents.
What else to study on this topic
- Structure and functions of the major histocompatibility complex (MHC II)
- Molecular mechanisms of B-lymphocyte activation
- The process of naive T-helper differentiation
- Contents of mast cell and basophil granules
- Mechanisms of anti-parasitic immunity
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