ICAO

IC3b

IC3b is a fragment of the complement component C3, which plays a crucial role in the immune system's response to pathogens. The complement system is a part of the innate immune system and consists of a series of small proteins that enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation, and attack the pathogen's cell membrane.

Structure and Formation

IC3b is formed from the cleavage of the complement component C3. The cleavage of C3 is a pivotal step in the activation of the complement system. When C3 is cleaved by the enzyme C3 convertase, it splits into two fragments: C3a and C3b. C3b can further undergo a conformational change to form iC3b, which is an inactivated form of C3b.

The conversion of C3b to iC3b is mediated by factor I, a serine protease, in the presence of cofactors such as factor H, complement receptor 1 (CR1), or membrane cofactor protein (MCP). This conversion is crucial for regulating the complement system and preventing damage to host tissues.

Function

IC3b plays a significant role in the immune response by acting as an opsonin. Opsonization is the process by which pathogens are marked for ingestion and elimination by phagocytes. IC3b binds to the surface of pathogens and facilitates their recognition and uptake by phagocytic cells such as macrophages and neutrophils.

IC3b interacts with complement receptors on phagocytes, particularly complement receptor 3 (CR3) and complement receptor 4 (CR4). This interaction enhances the phagocytosis of opsonized pathogens, leading to their destruction.

Regulation

The regulation of IC3b formation and activity is critical to maintaining balance in the complement system. Uncontrolled complement activation can lead to tissue damage and contribute to various inflammatory and autoimmune diseases. The conversion of C3b to iC3b is a key regulatory step that prevents excessive complement activation.

Clinical Significance

Dysregulation of the complement system, including the formation and function of IC3b, is implicated in several diseases. For example, improper regulation can lead to conditions such as atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE).

Therapeutic interventions targeting the complement system, including the modulation of IC3b activity, are being explored to treat these conditions. Understanding the role of IC3b in the immune response is essential for developing such therapies.

Also see

• Complement system
• C3 convertase
• Opsonization
• Phagocytosis
• Factor I
• Complement receptor 3