Complement c3b

Complement C3b is a crucial component of the complement system, which is part of the innate immune system. It plays a significant role in the opsonization of pathogens, facilitating their clearance by phagocytes.

Structure

Complement C3b is derived from the cleavage of complement component 3 (C3) by the enzyme C3 convertase. C3 is a large glycoprotein composed of an alpha and a beta chain linked by disulfide bonds. Upon activation, C3 is cleaved into C3a and C3b. The C3b fragment contains a reactive thioester bond that allows it to covalently attach to pathogen surfaces.

Function

C3b serves several critical functions in the immune response:

Opsonization

C3b acts as an opsonin, marking pathogens for destruction. It binds to the surface of microorganisms, enhancing their recognition and uptake by phagocytic cells such as macrophages and neutrophils. This process is facilitated by receptors on phagocytes, such as complement receptor 1 (CR1), which specifically bind to C3b.

Formation of C5 Convertase

C3b is also involved in the formation of the C5 convertase enzyme complex. When C3b binds to C3 convertase, it forms C5 convertase, which cleaves complement component 5 (C5) into C5a and C5b. C5a is a potent anaphylatoxin, while C5b initiates the formation of the membrane attack complex (MAC).

Immune Complex Clearance

C3b plays a role in the clearance of immune complexes from the circulation. By binding to immune complexes, C3b facilitates their transport to the liver and spleen, where they are removed by phagocytes.

Regulation

The activity of C3b is tightly regulated to prevent damage to host tissues. Several regulatory proteins control C3b activity:

• Factor H and Factor I: These proteins inactivate C3b by cleaving it into inactive fragments, such as iC3b.
• Decay-accelerating factor (DAF): This protein accelerates the decay of C3 convertase, reducing the production of C3b.
• Membrane cofactor protein (MCP): This protein acts as a cofactor for Factor I-mediated cleavage of C3b.

Clinical Significance

Dysregulation of C3b activity can lead to various diseases:

• Atypical hemolytic uremic syndrome (aHUS): Mutations in regulatory proteins can lead to excessive C3b activity, causing damage to endothelial cells and leading to aHUS.
• Age-related macular degeneration (AMD): Abnormal regulation of C3b has been implicated in the pathogenesis of AMD.
• Systemic lupus erythematosus (SLE): Deficiencies in C3b or its regulators can contribute to the development of SLE, an autoimmune disease characterized by the formation of immune complexes.

See Also

• Complement system
• Opsonization
• Phagocytosis
• Membrane attack complex