Antibodies as a gamma-globulin fraction
Antibodies are serum gamma-globulins. During electrophoretic separation of plasma proteins, alpha, beta, and gamma fractions are distinguished; immunoglobulins (Igs) belong precisely to the latter. The synthesis and secretion of antibodies are carried out by plasma cells — terminally differentiated derivatives of B lymphocytes. Antibodies are a key effector component of the humoral immune response: they specifically bind antigens, neutralize them, opsonize pathogens, and activate the complement system.
General structure of the immunoglobulin molecule
A classical monomeric Ig molecule (using the IgM or IgG monomer as an example) is constructed from four polypeptide chains connected by disulfide bonds. Its composition includes:
- Two heavy chains (H, heavy) — about 450 amino acid residues each, molecular weight 50–60 kDa per chain (and on the order of 100–120 kDa as a heavy chain dimer).
- Two light chains (L, light) — about 212 amino acids, mass 25 kDa each (totaling up to 50–60 kDa).
Between the H-chain pairs and between the H and L chains are disulfide bridges (S–S bonds), which maintain the quaternary structure of the molecule. It is customary to schematically depict a pair of disulfide bonds in the chain-joining region, but in fact, such bonds are distributed throughout the molecule.
Functional regions: Fab, Fc, and the hinge region
Functionally distinct fragments are distinguished within the immunoglobulin molecule:
- Fab fragment (Fragment antigen binding) — the antigen-binding site. Formed by the variable domains of the H and L chains, contains free NH₂ groups, and forms the antigen-binding center (paratope).
- Fc fragment (Fragment crystallizable) — the "stem" of the molecule, formed by the constant domains of the heavy chains. It is named for its ability to crystallize. It provides the effector functions of the antibody: binding to cellular Fc receptors (macrophages, neutrophils, mast cells), activation of the complement system, and transplacental transfer.
- Hinge region — a flexible segment between the Fab and Fc fragments. It provides mobility to the antigen-binding "arms," allowing the molecule to simultaneously bind antigens located at varying distances.
Domain structure of the Fc fragment
The heavy chains in the Fc fragment are organized into constant domains (CH1, CH2, CH3, and CH4 in IgM and IgE). Each domain performs a specific function:
- CH2 domain is responsible for binding to components of the complement system (primarily C1q) and bears glycosylation sites.
- CH3 domain mediates interaction with cell membrane Fc receptors — phagocytes and other effector cells, which facilitates opsonization and uptake of the antigen–antibody complex.
- Attached to the constant domains are carbohydrate chains, which influence the stability and functional activity of the molecule.
Classification of immunoglobulins by isotype
Isotype — the primary classification of antibodies based on the chemical structure of the chain constant regions. Isotypes are distinguished by heavy-chain type and light-chain type.
By H-chain type
- IgA — α-type heavy chain; subclasses IgA1 (α1) and IgA2 (α2). Predominates in mucosal secretions.
- IgG — γ-type; four subclasses IgG1, IgG2, IgG3, IgG4 (γ1–γ4). The main immunoglobulin of the secondary response, crosses the placenta.
- IgM — μ-type. The first antigen-binding immunoglobulin of the primary response, exists as a pentamer in serum.
- IgD — δ-type. Functions primarily as a membrane receptor on mature B lymphocytes.
- IgE — ε-type. Associated with mast cells and basophils, mediates type I hypersensitivity and anti-parasitic immunity.
By L-chain type
Light chains are represented by two types — κ (kappa) and λ (lambda). In a single immunoglobulin molecule, both light chains are always of the same type. The κ/λ ratio in the serum of a healthy person is approximately 2:1 and is used as a diagnostic indicator in monoclonal gammopathies.
Key points
- Antibodies are blood gamma-globulins produced by plasma cells, which are derivatives of B lymphocytes.
- An Ig molecule consists of 2 heavy (H, ~450 amino acids) and 2 light (L, ~212 amino acids) chains connected by disulfide bonds.
- The Fab fragment is responsible for antigen binding, while the Fc fragment is responsible for effector functions and interaction with cells and complement.
- The hinge region provides flexibility to the antigen-binding arms of the molecule.
- The CH2 domain binds complement, the CH3 domain binds cellular Fc receptors, and carbohydrate chains are attached to the domains.
- Based on the H-chain type, five isotypes are distinguished: IgA (α), IgG (γ), IgM (μ), IgD (δ), IgE (ε); IgA and IgG have subclasses.
- Based on the L-chain type, immunoglobulins are divided into κ and λ variants.
- Isotypic classification reflects the chemical structure of the constant regions and determines the biological properties of antibodies.