Textbook - BIOLOGICAL CHEMISTRY - Hubskyi Yu.I. - 2000

Chapter VI. BIOCHEMISTRY OF PHYSIOLOGICAL FUNCTIONS AND SPECIALIZED TISSUES

CHAPTER 30. BIOCHEMISTRY OF IMMUNE PROCESSES

30.2. IMMUNOGLOBULINS: STRUCTURE, BIOLOGICAL FUNCTIONS

IMMUNOGLOBULINS are a Class of Proteins that act as effectors of humoral Immunity, functioning as Antibodies by interacting with genetically foreign macromolecules known as Antigens. In human Blood, immunoglobulins exhibit the electrophoretic properties of γ-globulins, accounting for up to 20% of the total plasma protein mass.

Immunoglobulins are synthesized by plasma Cells, which develop from B lymphocytes when stimulated by an Immune Response to foreign proteins, cells (microorganisms, Protozoa), infectious diseases, vaccination, Organ and tissue transplantation, blood transfusions, or the malignant transformation of the body's own cells.

Immunoglobulin molecules are Glycoproteins whose protein component is a tetramer consisting of four polypeptide chains: two heavy (H) chains and two light (L) chains. In every individual immunoglobulin molecule, the two heavy and two light chains are pairwise identical; thus, the conventional formula for any immunoglobulin is represented as H₂L₂.

The H-chains of immunoglobulins consist of approximately 220 amino acid residues and have a Molecular Weight of 50-70 kD, whereas the L-chains contain about 110 amino acid residues with a molecular weight of 20-25 kD. The individual polypeptide chains within immunoglobulin molecules are interconnected by disulfide S-S bonds (Fig. 30.1). Oligosaccharide residues, composed of mannose and N-acetylglucosamine, are attached to the H-chains near their C-termini.

Fig. 30.1. Structural components of immunoglobulin molecules.

Each H- or L-chain of an immunoglobulin molecule contains distinct domains that differ in Structure and serve specific functional roles.

Constant regions (C-regions) are domains characterized by a uniform Amino Acid Composition across different classes of immunoglobulins. They are located at the C-termini of the L- and H-chains, occupying 1/2 of the length of the L-chain (C_L) and 3/4 of the length of the H-chain (C_H1, C_H2, and C_H3 domains).

Variable regions (V-regions) are located at the N-termini of the L- and H-chains. These regions comprise approximately 1/2 of the L-chain length (V_L) and 1/4 of the H-chain length (V_H). V-regions are characterized by a high Variability in amino acid composition. Through The amino acid residues of their hypervariable terminal segments, they form the antigen-binding site of the immunoglobulin molecule (the paratope), which is conformationally complementary to the determinant groups of the antigen, thereby ensuring specific binding.

Cleavage of immunoglobulins by Papain, which occurs at the hinge region of the molecule, yields two antigen-binding fragments (F_ab fragments) and a crystallizable fragment (F_c fragment).

The various types of heavy and light chains in immunoglobulin molecules are designated by Greek letters. According to this nomenclature, There are five types of H-chains (α, γ, μ, δ, ε) and Two Types of L-chains (κ, λ). Depending on the heavy chain type, five classes of immunoglobulins are distinguished (IgA, IgD, IgE, IgG, IgM), in each of which a specific H-chain type is paired with one of the two L-chain types. In biological systems (blood serum, other biological fluids, and Tissues), certain immunoglobulin classes form supramolecular complexes (n = 2 - 5).

The principal classes of human blood immunoglobulins mediating the HUMORAL IMMUNE RESPONSE to foreign antigens are immunoglobulins G and M. Immunoglobulins A act as antibodies within other biological fluids and secretions (milk, tears, and mucosal secretions of the Lungs and intestines). Immunoglobulins D and E are minor serum components that perform specialized supplementary Functions in complex immune and allergic reactions.

The properties of human blood immunoglobulins are summarized in Table 30.1.

Table 30.1. Biochemical characteristics of individual human immunoglobulin classes