Complement

Complement System

The complement system is a crucial part of the immune system, consisting of a series of small proteins that enhance ("complement") the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system and plays a role in the adaptive immune system as well.

History

The complement system was first discovered in the late 19th century by Jules Bordet, who demonstrated that blood serum contained a "complement" to antibodies that could kill bacteria. This discovery was pivotal in understanding the mechanisms of immune defense.

Components

The complement system consists of over 30 proteins, including:

• C1q, C1r, C1s
• C2, C3, C4, C5, C6, C7, C8, C9
• Regulatory proteins such as Factor H and Factor I

These proteins are primarily synthesized by the liver and circulate in the blood in an inactive form.

Pathways of Activation

The complement system can be activated via three pathways:

Classical Pathway

The classical pathway is triggered by antibodies bound to antigens, forming an antigen-antibody complex. This pathway involves the binding of the C1 complex (C1q, C1r, C1s) to the Fc region of antibodies, leading to a cascade of proteolytic activations.

Lectin Pathway

The lectin pathway is activated by the binding of mannose-binding lectin (MBL) to pathogen surfaces. This pathway is similar to the classical pathway but does not require antibodies.

Alternative Pathway

The alternative pathway is continuously active at a low level and can be amplified on pathogen surfaces. It involves the spontaneous hydrolysis of C3 and the formation of the C3 convertase complex.

Functions

The complement system has several key functions:

• Opsonization: Complement proteins coat the surface of pathogens, enhancing their uptake and destruction by phagocytes.
• Chemotaxis: Complement fragments act as chemoattractants, recruiting immune cells to sites of infection.
• Cell Lysis: The formation of the membrane attack complex (MAC) can directly lyse pathogen cell membranes.
• Immune Clearance: Complement helps in the removal of immune complexes and apoptotic cells.

Regulation

The complement system is tightly regulated to prevent damage to host tissues. Regulatory proteins such as CD55 (decay-accelerating factor) and CD59 (protectin) inhibit complement activation on host cells.

Clinical Significance

Dysregulation of the complement system can lead to various diseases, including:

• Hereditary angioedema
• Paroxysmal nocturnal hemoglobinuria
• Atypical hemolytic uremic syndrome

Complement deficiencies can result in increased susceptibility to infections, particularly with encapsulated bacteria.

See Also

• Immune system
• Antibody
• Phagocytosis

References

• Janeway, C. A., et al. (2001). Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science.
• Walport, M. J. (2001). Complement. First of two parts. New England Journal of Medicine, 344(14), 1058-1066.