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

Chapter VI. BIOCHEMISTRY OF PHYSIOLOGICAL FUNCTIONS AND SPECIALIZED TISSUES

CHAPTER 30. BIOCHEMISTRY OF IMMUNE PROCESSES

30.4. BIOCHEMICAL COMPONENTS OF THE COMPLEMENT SYSTEM

Complement is an enzymatic system required for the lysis of foreign Cells (bacterial, animal) following their interaction with specific Antibodies. Biochemically, complement Proteins form a cascade system of proteases that are sequentially activated upon The formation of the antigen-antibody complex, causing the degradation of membrane structures of cells destined for destruction during the Immune Response.

There are nine main components (protein subunits) of The Complement System, designated as C1, C2, C3, C4, C5, C6, C7, C8, and C9. Subunit C1 is a complex consisting of three proteins: C1q, C1r, and C1s. Under physiological conditions, the protein Components of the complement system circulate in Blood Plasma in an inactive state. Activated forms of complement proteins are indicated by a bar over the corresponding Roman numeral: C₁, C₂, etc. The Biochemical characteristics of human complement system proteins are presented in Table 30.2.

Class="center">Table 30.2. Proteins of the human complement system

* E.N. Shlyakhov, L.P. Andriesh, 1985

Activation of the complement system proceeds via one of two mechanisms: the classical or The alternative pathway (Fig. 30.2). Regardless of the pathway involved, the key event in complement activation is the activation of the C3 component, which exhibits autocatalytic properties and triggers a cascade of Enzymatic reactions involving the terminal components C7, C8, and C9.

Fig. 30.2. Activation of complement via the classical (a) and alternative—properdin (b) pathways (Ag — antigen).

The classical pathway of complement activation is a sequence of enzymatic reactions triggered by the interaction of the first complement component, C1, with the complement-fixing regions of antibodies (IgG, IgM) that have formed an antigen-antibody complex on The Cell surface.

The binding of component C1 to IMMUNOGLOBULINS fixed on the cell surface is mediated by the C1q protein, known as the recognition factor. The interaction of C1q with the antibody leads to the activation of the C1r subunit, which cleaves the C1s molecule, converting the latter into an active Serine proteinase. This initiates the trigger mechanism of complement system activation.

The substrates of the active proteolytic enzyme C1s are components C4 and C2, which are sequentially cleaved into their respective molecular fragments: active C4b and inactive C4a, along with active C2a and inactive C2b. The active C4bC2a complex is termed C3 convertase. It cleaves the active protease C3b (C5 convertase) from the C3 component, which in turn activates The system of terminal complement components (C5–C9).

The activated terminal components form a supramolecular protein complex (C5b, C6, C7, C8, C9) on The cell membrane surface, causing membrane lysis—that is, The breakdown of its protein-lipid bilayer. Under the Influence of the lytic complex, transmembrane channels up to 10 nm in diameter are formed, through which Ca²⁺ and Na⁺ freely enter the cell and K⁺ is lost, ultimately resulting in cell destruction.

The alternative (properdin) pathway of complement activation does not require the participation of immunoglobulins and likely holds biological significance during the Cytology/cytology/16.html">Early stages of the host's defense against infectious agents, before sufficient quantities of antibodies are produced.

Similar to the classical pathway, the alternative pathway also involves the activation of the C3 complement component to form C5 convertase, but without the involvement of components C1, C2, and C4. The initial step here is the interaction of bacterial Antigens (Polysaccharides, lipopolysaccharides of the gram-negative Cell wall, etc.) with the proteins of the properdin system.

The properdin system consists of three proteins: protein P (properdin proper), protein B, and protein D (a serine proteinase). Introduction/37.html">Bacterial cell wall antigens induce the sequential activation of factors P, D, and B. Activated factor B (Bb) cleaves the principal complement component, C3, to form the C3bBb C5 convertase, which activates the C5 component responsible for the Formation of the membrane attack complex.