Select proteins, carbohydrates, viruses, and bacteria can activate Clq in the fluid phase and without antibody. Polyanions such as polyinosine, polyguanilic acid, lecithin, and sphingomyelin are potent activators. C-reactive protein (CRP) can also activate Clq indirectly following interactions with polyanions.
Proteins that are part of the innate immune defense system also activate Clq. Mannose-binding protein (MBP) and membrane-associated serine protease (MASP) activate complement because they mimic the structure of Clq (Turner, 1996).
Viruses can indirectly activate the classical pathway. Oncornaviruses such as the Moloney leukemia virus and vesicular stomatitis viruses have a membrane receptor for Clq (Volanakis, 1975) that activates Clq
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