Exploring the Integral Role of C3d in the Complement System and Innate Immunity
The complement system is a vital component of innate immunity, with the third complement component, C3, playing a central role in the classical, alternative, and lectin pathways of complement activation. This article emphasizes the significance of C3 and its by-product, C3d, in immune system functioning.
The Diversity and Activation of C3 in Immune Responses
Activation products of the complement cascade, including C3d, contain unique neo-epitopes, which are absent in the native components. These neo-epitopes are crucial for the system’s response to pathogens. The synthesis of C3, from which C3d derives, is tissue-specific and adjusts in response to various stimulatory agents, demonstrating its adaptability in immune regulation.
C3 Abundance and the Implications of its Deficiency
C3 is notably the most abundant protein in the complement system, with serum levels around 1.3 mg/ml. Interestingly, an inherited deficiency of C3, and consequently C3d, predisposes individuals to more frequent bacterial infections, highlighting their importance in disease prevention.
In conditions like ulcerative colitis and chronic inflammatory bowel disease, the deposition of C3 and C3d in diseased mucosa has been observed, indicating their role in immunopathology.
The Proteolytic Journey
The journey of C3, leading to the formation of C3d, begins with its cleavage by C3-convertases into C3a and C3b. C3b, upon attaching to immune complexes, undergoes further cleavage into iC3b and C3f. The subsequent processing of iC3b results in C3c and C3dg. Notably, C3dg can be further cleaved into C3d and C3g. It is important to note that the formation of C3d, a crucial step in immune response modulation, does not occur in plasma.
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Immuno assays, Immuno precipitation