The complement system is composed of a group of soluble proteins present in human or vertebrate serum and tissue fluid, and a group of membrane-bound proteins and complement receptors present on the surface of blood cells and other cells.

It is responsible for anti-infection and immune regulation in the body’s immune system, and participates in immune pathological reactions.

Complement is an important part of innate immunity.

The Discoverer of Complement

1894 Bordet found that sheep anti-cholera serum can dissolve Vibrio cholera at 56°C for 30 min and prevent its activity. Ehrlich independently discovered a similar phenomenon at the same time, and named it as Complement

The Composition of Complement System

a. Complement molecule: C1~C9, B, D, P factors, C1INH, C4BP, H, I, S protein

b. Complement receptor: C1qR, C3b/C4bR (CRI), 3dR (CRID), factor H receptors, C3a and C5a receptors, etc.

The Composition of Complement Molecule

The first component is composed of 9 kinds of complement components, named C1,2... C1 is composed of three subunits, named Clq, Clr, Cls, so the first component is composed of 11 globulins.

The second component: In the 1970s, it was discovered that some new serum factors are also involved in complement activation, but they are not through the activation pathway of the antigen-antibody complex, but through the alternative activation pathway. These factors include factor B, factor D and factor P.

The third component: a variety of inhibitors or inactivation factors involved in the control of complement activation, such as C1 inhibitors, factor I, factor H, C4 binding protein allergic toxin inactivation factor, etc. These factors can control the activation of complement molecules and regulate the maintenance of complement balance in the body.

Physicochemical properties of complement molecules

1. Produced by a variety of cells such as hepatocytes, macrophages, and intestinal mucosal epithelial cells are polysaccharide proteins, most of the electrophoretic mobility belongs to a, Y globulin.

2. The content accounts for about 10% of the total serum globulin, with the highest C3 content and the lowest D factor content.

3. The molecular weight difference between the inherent components is large, among which C1q is the largest and D factor is the smallest.

4. It is unstable to heat. It is inactivated at 56°C and 30min, and the activity can only be maintained for 3~4d under the condition of 0~10°C.

5. Various physical and chemical factors such as radiation, mechanical oscillation, alcohol, bile, and certain additives can destroy complement.

Activation of the complement system

The components of the complement system usually exist in the plasma in an inactive state, and when they are activated by the activated substance, they exhibit various biological activities.

Classical pathway: Initiation by antigen-antibody complex binding to C1q.

The classical pathways are divided into three groups according to their role in the activation process:

1. Identification unit: including C1q, C1r, C1S.

2. Activation unit: including C4, C2, C3.

3. Membrane attack unit: including C5~9.

Alternative pathway: the contact surface is provided by pathogenic microorganisms, etc., and activation starts from C3.

The activation substance of bypass activation is the cell wall component of bacteria (lipopolysaccharide, peptidoglycan, phosphoric acid and condensed substances such as IgA and IgG).

(1) Under physiological conditions: C3 interacts with factors B, D, etc. few C3b and C3bBb (the C3 convertase of the alternative pathway), but is rapidly destroyed by factor H and factor.

(2) Activation of the alternative pathway: when bacterial lipopolysaccharides, peptidoglycans, viruses, tumor cells, etc.

When the activation substance appears, factor H and factor I cannot inactivate C3b, C3bBb, so that the alternative pathway is activated.

(3) Expansion of activation effect: When C3 is activated, it is cleaved into C3b, and C3b can synthesize new C3bBb with the participation of factors B and D, which further promotes the cleavage of C3, and there are abundant C3, factor B, and Mg2+ in the plasma. It may have a significant expansion effect at the activation site, which is a positive feedback pathway for C3b.

The MBL pathway: initiated by MBL binding to bacteria.

Comparison of two activation pathways

The two activation pathways have something in common:

(1) Both pathways are a chain reaction of complement components;

(2) Many components are cracked into large and small two fragments after successive activation;

(3) Different fragments or their complexes can move forward on the surface of target cells to form complexes in situ at the activation site.

Regulation of the complement activation process

The activation of the complement system must be carried out under moderate regulation in order to play a normal physiological role. If the activation of complement is out of control, a large amount of complement will be consumed unnecessarily, resulting in a decline in the body’s ability to infect, and will cause the body to undergo a severe inflammatory reaction or cause damage to its own tissue cells.

The regulation of the complement activation pathway mainly includes:

(1) Regulation of complement decay

(2) The role of soluble complement regulatory factors

(3) The role of membrane complement regulatory proteins and complement receptors

Regulation of self-decay

The cleavage products of some complement components are extremely unstable and prone to decay on their own, becoming a self-control mechanism in the process of complement activation. For example, C2b in C4b2b decays on its own, preventing it from continually activating C3, limiting the chain reaction of subsequent complement components.

The role of soluble complement regulatory factors

(1) C1 inhibitor (C1 INH); can irreversibly bind to C1, so that the latter loses esterase activity, no longer cleaves C4 and C2, and no longer forms C4b2b (C3 invertase), thereby blocking or reduce the response of subsequent complement.

(2) C4 binding protein (C4bp); can competitively inhibit the binding of C4b and C2b, and therefore can inhibit the formation of C42.

(3) Factor I (also known as C3b inactivation factor, C3binactivator, C3bINA): It can cleave C3b to make it inactive C3bi, so that both C4b2b and C3bBb lose the opportunity to combine with C3b to form C5 convertase.

(4) Factor H: Factor H not only promotes the speed of factor I inactivating C3b, but also competitively inhibits the combination of factor B and C3b, and also allows C3b to be replaced from C3bBb to accelerate its inactivation. .

(5) S protein: S protein can disturb the binding of C5b67 to cell membrane.

(6) C8 binding protein (C8bp) (also known as homologous restriction factor, HRF): C8bp can prevent the binding of C8 and C9 in C5678, thus avoiding the damage to the cell membrane.

To be continued in Part II…

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