The complement system stands as a pivotal element within the innate immune system, orchestrating a series of responses aimed at identifying and eliminating pathogens while triggering inflammation. However, dysregulation of this system can lead to inflammatory and autoimmune disorders.
Comprising a group of serum proteins, the complement system activates via three pathways: classical, alternative, and lectin, converging to generate C3 convertase. This enzyme cleaves C3 into C3a, an anaphylatoxin that enhances inflammation, and C3b, an opsonin that tags pathogens for phagocytosis. Further activation yields C5 convertase, facilitating the formation of the membrane attack complex (MAC), which disrupts target cell membranes, causing cell lysis.
Central to these processes is C3, linking innate and adaptive immunity to combat infections effectively. Tools such as the C3a ELISAÂ assay quantify C3a levels in biological samples, aiding in understanding complement system activation and regulation in disease.
The MAC, a final complement product, forms pores in cell membranes, lysing pathogens like bacteria and virus-infected cells. Its formation via protein cleavage and activation through the complement pathways involves sequential binding and polymerization.
While crucial for immune defense, complement system imbalance underlies disorders like Paroxysmal Nocturnal Hemoglobinuria (PNH), Atypical Hemolytic Uremic Syndrome (aHUS), and complement-mediated kidney diseases. PNH results from red blood cells lacking protective proteins, vulnerable to MAC-induced hemolysis. In aHUS, deficiencies in complement regulatory proteins lead to excessive activation, damaging endothelial cells and causing thrombus formation.
Therapeutically, complement inhibitors like Eculizumab and Ravulizumab block C5 cleavage, preventing MAC formation and treating PNH and aHUS. Avacopan, a C5aR1 antagonist, targets ANCA-associated vasculitis.
Ongoing research into complement biology and inhibitors promises improved therapies for immune-related diseases. Emerging studies on C5a and MAC in the tumor microenvironment suggest potential applications in cancer treatment. Deeper insights into complement function and therapeutics offer hope for managing a broad spectrum of diseases effectively.
