C3b, iC3b, C3c, Human, clone C3-42.3

The Integral Role of C3b, iC3b, and C3c in the Complement System and Immune Response

The complement system is a pivotal component in both innate and adaptive immune responses, capable of producing inflammatory and protective reactions to pathogenic challenges. This article highlights the significant roles of C3b, iC3b, and C3c in this vital system.

Complex Activation Pathways Leading to C3b, iC3b, and C3c Formation

Comprising a complex family of proteins and receptors, the complement system operates in circulation, tissues, and other body fluids. It activates through three pathways: the classical pathway, initiated by immune complexes; the lectin pathway, triggered by surface-bound lectins; and the alternative pathway (AP), activated by unprotected surfaces. Each pathway generates a C3 convertase, a serine protease that cleaves the central protein C3, leading to the creation of C3b.

C3 Convertases: Driving the Complement Cascade

C3 and C5 convertases are enzymatic complexes critical for initiating and amplifying complement activity, ultimately generating the cytolytic membrane attack complex (MAC). The synthesis of C3, which leads to the formation of C3b, iC3b, and C3c, is tissue-specific and responsive to various stimulatory agents. Following cleavage by C3 convertase, C3 yields anaphylotoxin C3a and the crucial fragment C3b.

The Abundance and Functionality of C3 and Its Derivatives

C3, with a molecular weight of approximately 185 kDa, is the most abundant protein in the complement system. Its primary production occurs in the liver, but it’s also generated by macrophages, neutrophils, and other cells. Due to its high levels and low biological reactivity, C3 can respond swiftly and effectively to pathogens. However, defects in C3 can lead to recurrent infections or autoimmune diseases. C3 deficiency, though rare, results in significant health challenges, including recurrent infections and impaired immune cell development. Polymorphisms in C3 have been linked to conditions like age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS).

The Significance of C3b, iC3b, and C3c in Disease and Immune Regulation

Besides pathogen clearance, C3, particularly through its fragments C3b, iC3b, and C3c, aids in the removal of circulating immune complexes, enhancing macrophages’ phagocytic capacity. Malfunctions in this system can lead to autoimmune diseases and tissue damage. Thus, understanding the roles and interactions of C3b, iC3b, and C3c is crucial in diagnosing and managing various immune-related conditions.

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