COMPLEMENT FUNCTIONS IN INNATE AND ADAPTIVE IMMUNITY

The complement system evolved as part of innate immunity and as such it has an important role in host defense. Complement exhibits the four fundamental properties of innate immunity: (a) its components are encoded by the germ line, (b) its genes are invariant within a species, (c) it is constitutively poised for activation, and (d) it recognizes and is activated by large molecular motifs associated with viral, bacterial, and fungal pathogens – the so-called pathogen-associated molecular patterns, or PAMPs (1). Pathogens do not express PAMPs by choice. PAMPs are associated with critical prokaryote function, such as the barrier functions of the outer membrane lipopolysaccharide (LPS) of gram-negative bacteria and the cell wall lipoproteins of gram-positive bacteria. Many of the most virulent bacterial pathogens have evolved polysaccharide capsules as a counterdefense mechanism to cover and hide their PAMPs and thereby evade recognition by complement.

Adaptive immunity, of a type similar to that of modern mammals, evolved in the ancestors of present day jawed fish. In contrast to innate immunity, adaptive immunity (a) encodes its genes in peripheral cells (lymphocytes); (b) allows mutation and selection of genes to adapt to the antigenic experience of the individual, as opposed to the species; (c) takes 1 to 3 weeks togenerate anewresponse; and (d) recognizes molecular details of antigens. Animals with adaptive immunity retain innateimmunity, including complement, to provide a first line of defense during the interval (1–3 wks) necessary to mount a new specific adaptive immune response. In addition, when innate immunity recognizes what is dangerous, it activates antigen-presenting cells and thereby provides critical priming for an adaptive immune response (2).