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I've been reading about the complement system, as part of the human immune system. The complement system is introduced as part of the article on innate immunity on Wikipedia. This classification makes obvious sense in the case of the alternative pathway, which is obviously not dependent on any specific pathogen.

However, I'm confused about whether this is an appropriate classification for the classical pathway (and, therefore, the system writ large) since the classical pathway is activated by antigen:antibody complexes and only by certain antibody isotypes (IgG and IgM). It is, therefore, to some extent pathogen specific and it is also, clearly, activated by and dependent upon the humoral immune response (generally classed as part of adaptive immunity).

So, in short, is it best to classify the complement system as part of the innate immunity (and, if so, why is that?), or would it be better to restrict ourselves to the observation that it is, to a greater or lesser extent, part of both types of immunity?

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1 Answer 1

Yes, the complement system is part of the innate immune system. It can be activated by the:

  • classical pathway (activated through bound IgM and IgG molecules but also by DNA, collagen (both are usually not available freely outside of cells) and c-reactive protein)
  • lectin pathway (activation by binding of mannose through the mannose binding lectin on the cell surface)
  • alternative pathway (activation by the constant hydrolysis of the complement component 3 (or C3) in an antibody independent way)

My guess here would be, that the classical activation via antibodies is evolutionary younger than the other two possibilities which act more directly on bacteria and do not depend on the availability of specific (at least to some degree) antibodies. The Wikipedia article on the complement system is pretty extensive.

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Just to underline that last point from @Chris - the signature property of the complement system is the use of proteins with reactive thioester groups to covalently tag cells, and this is very ancient. The plugging together of antibodies and the complement system is certainly a relatively recent innovation. The OP raises what is really a semantic point. There are also interactions between cellular immunity and humoral immunity, but it is still useful to think of these as separate processes with an interface. –  Alan Boyd Jan 6 at 15:42
    
Its also a matter of time: Generation and maturation of highly specific antibodies takes some time (the peak of new antibodies after an immunization comes after 14 days) while the innate immune system can kick in instantaneous. Its reaction is less specific and can probably be overcome by some bacteria, but its still pretty effective first line of defense. –  Chris Jan 6 at 15:47

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