Complement system

Complement pathway

Membrane Attack Complex (Terminal Complement Complex C5b-9)

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Complement-pathways

Complement system is a crucial part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is a complex network of protein molecules, known as complement proteins, that circulate in the blood plasma. These proteins work together in a series of cascading steps to identify and attack bacteria, viruses, and other foreign invaders.

Overview

The complement system consists of over 30 proteins and protein fragments, including serum proteins, serine proteases, and receptors that are synthesized mainly by the liver. The system is activated through one of three pathways: the classical complement pathway, which is triggered by antibody-antigen complexes; the lectin pathway, which is initiated by mannose-binding lectin binding to specific sugars on the surface of microbes; and the alternative pathway, which can be activated directly by pathogen surfaces.

Once initiated, these pathways converge on the central component of the system, C3, leading to the activation of the late components of the complement system that form the membrane attack complex (MAC). The MAC creates pores in the cell membranes of pathogens, leading to their lysis and death.

Functions

The complement system has several key functions in immune defense, including:

• Opsonization - enhancing phagocytosis of antigens
• Chemotaxis - attracting macrophages and neutrophils
• Cell lysis - rupturing membranes of foreign cells
• Agglutination - clumping of antigen-bearing agents
• Immune clearance - removal of immune complexes from circulation

Regulation

The activity of the complement system is tightly regulated by complement control proteins to prevent damage to host cells. Regulatory proteins such as Factor H and Factor I prevent the complement system from being inappropriately activated, which could result in damage to host tissue.

Clinical Significance

Dysregulation or genetic deficiencies in the complement system can lead to increased susceptibility to infections, autoimmune diseases, and other immune system disorders. Conversely, excessive activation of the complement system can contribute to inflammatory diseases. Therapeutic interventions targeting the complement system are being explored for a variety of diseases, including rare diseases, autoimmune diseases, and cancer.

See Also

• Immune system
• Inflammation
• Antibody
• Pathogen