Complement
The term complement, like many things in immunology is an historical term. The ability of components of plasma to bind to antigens and to agglutinate (IgM cross-linkage achieves this) was already understood. It was then demonstrated that blood plasma (cell-free fraction of blood) had the 'complementary ability' to kill bacteria.
Complement not only kills bacteria directly but also plays a part in triggering the acute inflammatory response and some components are able to act as opsonins. These are all very powerful reactions and their activity in the absence of infection would be very dangerous, therefore the process must be well controlled. Like many biological systems that are tightly controlled, complement is a cascade. A cascade is a very simple concept. One activated enzyme activates the next, usually by cleaving a pro-enzyme to release a smaller product that is active.
In Complement the components are named in the order they were
discovered and are given the letter C, such as C2, C3 etc. When a component is
cleaved to two products, the smaller one is named a and the larger b; i.e. C3a
and C3b. There are also a number of factors in the cascade that are named by
letter; e.g. FB (Factor B) and FD (Factor D). The first molecule identified
(C1) is in fact made up of three subunits and so these are named C1q, C1r and C1s.
A line above a factor indicates it is activated – C1r (inactive) 
(active).
There are three major pathways of complement:
The Classical Pathway was the first discovered (hence its name) and is activated by antibody bound to a pathogen (it can be therefore be considered as part of the adaptive immune system).
The Alternative Pathway (named as it is alternative to the classical pathway) is triggered by generic bacterial antigens and does not in anyway depend on antigen specificity (hence it is part of the innate immune system).
The MBL (mannan-binding lectin) is the most recently discovered and uses many of the same components as the Classical Pathway.
All of these pathways converge in the Terminal Pathway which results in the production of a molecule termed the Membrane Attack Complex which, as its name suggests, damages membranes and is thus cytotoxic.
At first glance, the pathways are immensely complex, but when considered in a step-wise manner they are actually quite straight-forward;
Each of the following is a power-point presentation that illustrates how the pathway works:
The presentations are animated and a box in the bottom right corner indicates when it is necessary to click on the button on the bottom right corner for the next slide.
In addition to producing the membrane attack complex these molecules are also active in the immune system:
· C5b.6.7.8 is cytotoxic
· C3b is an opsonin
· C3a is a mediator of inflammation
· C5a is also a mediator of inflammation and has 10x the potency of C3a (C3a has 10x the concentration of C5a)
· C4a is another mediator of inflammation
· C5b.6.7 is a chemoattractant for neutrophils and basophils
Whilst Complement has the dramatic effect of lysing cells directly it is probably relatively unimportant in the immune system as experimental animals lacking complement are not especially immunocompromised.
