Figure 24–5 Antibody-activated phagocytosis. electron micrograph of a neutrophil phagocytosing an antibody-coated bacterium, which is in the process of dividing. The process in which antibody (or complement) coating of a pathogen increases the efficiency with which the pathogen is phagocytosed is called opsonization. (courtesy of Dorothy F. Bainton, from r.c. Williams, Jr. and h.h. Fudenberg, phagocytic Mechanisms in health and Disease. New York: Intercontinental Medical Book  corporation, 1971.)
If a pathogen is too large to be successfully phagocytosed (if it is a large parasite such as a worm, for example), a group of macrophages, neutrophils, or eosinophils (another type of leukocyte) will gather around the invader. They secrete defensins and other damaging agents and release the toxic products of the respiratory burst. This barrage is often sufficient to destroy the pathogen (Figure 24–6).
The blood and other extracellular fluids contain numerous proteins with antimicrobial activity, some of which are produced in response to an infection, while others are produced constitutively. The most important of these are components of the complement system, which consists of about thirty interacting soluble proteins that are mainly made continuously by the liver and are inactive until an infection or another trigger activates them. They were originally identified by their ability to amplify and “complement” the action of antibodies made by B cells, but some are also secreted PRRs, which directly recognize PAMPs on microbes.
The early complement components consist of three sets of proteins, belonging to three distinct pathways of complement activation—the classical pathway, the lectin pathway, and the alternative pathway. The early components of all three pathways act locally to cleave and activate C3, which is the pivotal complement component (Figure 24–7); individuals with a C3 deficiency are subject to repeated bacterial infections. The early components are proenzymes, which are activated sequentially by proteolytic cleavage. The cleavage of each proenzyme in the series activates the next component to generate a serine protease, which cleaves the next proenzyme in the series, and so on. Since each activated enzyme cleaves many molecules of the next proenzyme in the chain, the activation of the early components consists of an amplifying proteolytic cascade.
Many of these protein cleavages liberate a biologically active small fragment that can attract neutrophils, plus a membrane-binding larger fragment. The binding of the large fragment to a cell membrane, usually the surface of a pathogen, helps stimulate the next reaction in the sequence. In this way, complement activation is largely kept confined to the cell surface where it began. In particular, the large fragment of C3, called C3b, binds covalently to the surface of the pathogen. Here, it recruits protein fragments produced by cleavage of other early complement components to form proteolytic complexes that catalyze the subsequent steps in the complement cascade. The early events in complement activation have diverse functions: C3b-binding receptors on phagocytic cells enhance the ability of these cells to phagocytose the pathogen, and similar receptors on B cells enhance the
Figure 24–6 eosinophils attacking a parasite. phagocytes cannot ingest large parasites such as the schistosome larva shown here. When the larva is coated with antibody or complement components, however, eosinophils (and other leukocytes) can recognize it and collectively kill it by secreting a large variety of toxic molecules. (courtesy of Anthony Butterworth.)