Molecular Structure Features
All proteins discussed feature a distinct domain structure. The simplest antibody molecule is composed of four polypeptide chains held together by numerous non-covalent interactions and four disulfide bonds:
- Light chains (L): two identical structures, each approximately 220 amino acids long.
- Heavy chains (H): two identical structures, ranging from 440 to 700 amino acids long.
Each immunoglobulin domain adopts a $\beta$-sheet super-structure further stabilized by a disulfide bridge. Light chains contain two domains: a variable domain ($V_L$) at the N-terminus and a constant domain ($C_L$) at the C-terminus. Heavy chains typically contain one variable domain ($V_H$) and three or four constant domains ($C_H$).
To ensure molecular mobility, a hinge region is located between the $C_{H1}$ and $C_{H2}$ domains. It contains a high concentration of proline amino acid residues. This prevents the formation of a rigid secondary structure, stops adjacent heavy chains from clumping together, and grants the entire complex necessary flexibility.
Antigen-Binding Sites and Mechanism of Action
Antibodies serve as a front line against foreign agents. The ability to recognize a target resides in the antigen-binding sites (active centers) located at the N-termini of the molecule—between the $V_H$ and $V_L$ variable domains.
Active center formation involves not the entire protein sequence, but only 20–30 amino acids located within hypervariable regions. Because the basic molecule has two such identical regions, antibodies are termed bivalent.
The functional process occurs in two stages:
- Recognition and binding. This takes place on the pathogen's surface. Attaching a target to the antigen-binding site induces conformational changes in the constant domains.
- Initiation of inactivation. The subsequent fate of the complex depends on the antibody's class. This stage triggers mechanisms of antigen destruction and clearance.
Classes of Immunoglobulins
Immunoglobulin classification is based on the structural features of the constant domains of their heavy chains (types $\alpha, \delta, \epsilon, \gamma, \mu$). The structure of the heavy chains and hinge regions determines the unique conformation of each class.
- IgG (Immunoglobulin G). Predominates in blood (75%). Exists as monomers. These are the main antibodies of the secondary immune response. They activate the complement system, bind to macrophage receptors, and induce phagocytosis. Special property: This is the only class capable of crossing the placental barrier to provide intrauterine protection to the fetus.
- IgM (Immunoglobulin M). Exists in two forms. The monomeric form (featuring a tail of 25 hydrophobic amino acids) is embedded in the B-lymphocyte membrane as a receptor. The secretory form is a massive pentamer held together by disulfide bonds and a J chain. It possesses 10 binding sites. This is the first antibody class secreted during a primary immune response; it efficiently activates complement to lyse bacterial membranes.
- IgA (Immunoglobulin A). The principal antibodies of secretions (saliva, milk, respiratory and intestinal tract mucus). Secreted as dimers linked by a J chain. They do not activate complement or macrophages, but effectively bind microbes, blocking their adhesion to the epithelium.
- IgE (Immunoglobulin E). Monomers whose heavy chain features one variable and four constant domains. Their C-termini anchor to receptors on mast cells and basophils. Upon antigen binding, the cell receives a signal to release histamine and serotonin, leading to inflammation and allergies (urticaria, hay fever, asthma).
- IgD (Immunoglobulin D). Monomers present in trace amounts in serum. Heavy chains contain three constant domains. They act as surface receptors on B lymphocytes; upon antigen binding, they transmit a signal inside the cell, triggering clonal proliferation.