The Role of Antigen Processing and Presentation

1. Complement: A Versatile Backup System

Among its many overlapping functions, the immune system has another complex and multiple-duty system called complement that, like inflammation and phagocytosis, is brought into play at several levels. The complement system, named for its property of “complementing” immune reactions, consists of at least 26 blood proteins that work in concert to destroy a wide variety of bacteria, viruses, and parasites. The sources of complement factors are liver hepatocytes, lymphocytes, and monocytes.

Complement functions as a positive feedback loop or cascade reaction. Its primary action is a sequential physiological response like that of blood clotting, in which the first substance in a chemical series activates the next substance, which activates the next, and so on, until a desired end product is reached.

Three different versions of the complement pathways exist (figure 1).Their main distinguishing features are how they are activated, major participating factors, and specificity. The end stages of all three converge at the same point and yield a similar end result, that is, destruction of a pathogen. The classical pathway is the most specific, activated mainly by the presence of antibody bound to microorganisms. The lectin pathway is a nonspecifi c reaction of a host serum protein that binds a sugar called mannan present in the walls of fungi and other microbes. (Proteins that bind carbohydrates are called lectins.)

The alternative pathway begins when complement proteins bind to normal cell wall and surface components of microbes. Note that because the complement numbers (C1 to C9) are based on the order of their discovery, some factors are not activated in numerical order.