The complement system is a part of the immune system. It consists of more than 30 proteins and is used to defend against bacteria, fungi or parasites.
What is the complement system?
The complement system is a part of the immune system. It consists of more than 30 proteins and is used to defend against bacteria, fungi, or parasites. The complement system was discovered by Jules Bordet, whereas the name goes back to Paul Ehrlich. The system consists of various plasma proteins. Plasma proteins are proteins that mostly circulate in the blood. However, a small proportion of plasma proteins are also present in cell-bound form. The main components of the complement system are the complement factors C1 to C9, MBL (mannose-binding lectin) and the serine proteases bound to C1 and MBL. These are referred to as C1r, C1s, and MASP-1 to MASP-3. The majority of plasma proteins are formed in the liver. The complement factors C1 to C5 can be cleaved by special protein-cleaving enzymes, the proteases. This results in the formation of various new proteins. Further protein complexes are formed by a combination of the factors C1 to C5 with the factors C6 to C9. For regulation, the complement system has so-called negative regulators, such as the C1 inhibitor or factor I. Activation of the complement system can occur via the classical pathway, the lectin pathway and the alternative pathway. In each of these pathways, a cascade reaction is initiated.
Function and task
The classical pathway for activation of the complement system begins with complement factor C1. C1 binds to an antigen-antibody complex. An antigen-antibody complex in this case is a cell labeled with the antibodies IgG or IgM. When C1 has bound to this complex, various reactions take place within the protein. A subunit is formed that activates complement factor C4. The active components of C4 in turn bind to C2. From the combination of a subunit of C4 and C2, complement factor C3 is activated. The activated C3 serves as a marker for so-called antigenic cells. This labeling is also called opsonization. The complement factor C3 thus shows the scavenger cells (macrophages) that this marked cell is a cell that must be removed. Without this opsonization, macrophages would not recognize many pathogens. C5 convertase is also formed from various subunits of complement factors. This ensures the activation of complement factor C5. After activation, the factor is called C5b. C5b ensures the formation of a lytic complex. This destroys the cell membrane of the bacteria. Water can flow in through the holes that form in the cell membrane, so that the bacteria eventually burst. The alternative complement activation does not require antibodies. Here, activation occurs through a spontaneous decay of complement factor C3. This is chemically unstable. The resulting C3a can initiate an inflammatory reaction. In addition to C3a, C3b is also formed. C3b remains active only when it binds to pathogenic surfaces. If it circulates in the blood for too long or binds to endogenous cells, it is inactivated. This is important because otherwise autoimmune reactions would occur. On the surface of pathogens, C3b has a similar effect to C3 in the classical activation pathway. MBL activation occurs through the binding of mannose. Mannose is sugar found on bacterial surfaces. In the course of the cascade reaction, MASP-1 to MASP-3 are activated. They elicit the same reactions as classical complement activation.
Diseases and ailments
When there are deficiencies in complement factors, various diseases can result. A deficiency in the C1 inhibitor leads to an excessive response of the complement system. This deficiency may be congenital or acquired. The consequence of a C1 inhibitor deficiency is angioedema. This is a recurrent swelling of the organs, skin or mucosa. These swellings are caused by excessive release of anaphylatoxins. The resulting edemas are reddened and painful. They occur preferentially around the lips, on the extremities, or on the genitals. Swelling in the gastrointestinal tract can result in cramps and severe pain. People with deficiencies of complement factor C2 suffer more frequently from immune complex diseases.Thus, a deficiency of C1q, a precursor of C2, is a significant risk factor for the development of systemic lupus erythematosus (SLE). SLE is a rather rare autoimmune disease that affects the skin and other organs. The disease belongs to the group of collagenoses and thus also to the rheumatic group of forms. Mostly women of childbearing age are affected by SLE. With a deficiency of C3, bacterial infections occur much more frequently. In particular, infections with neisseria become more frequent. Neisseria are the causative agents of gonorrhea and meningitis. Due to a mutation, the inhibitory factor H may be missing. This leads to an uncontrollable activation of the complement system at the renal corpuscles and at the eye via the alternative pathway. The deposits cause membranoproliferative glomerulonephritis type II. Hematuria, proteinuria and a nephrotic or nephritic syndrome with water retention and high blood pressure occur. Visual disturbances are also possible. If there are defects in the GPI anchors on blood cells, these are no longer protected from the complement system. This causes the so-called paroxysmal nocturnal hemoglobinuria. The red blood cells are destroyed. This process is also called hemolysis. Furthermore, the disease is associated with an increased tendency to thrombosis and a decreased production of red blood cells in the bone marrow. Other symptoms include chronic fatigue, impotence problems and severe pain. Possibly not only the red blood cells, but all blood cell series are affected by the attacks of the complement system. In these cases, in addition to the tendency to thrombosis, there is also a marked weakening of the immune system.
