Once C5b has been produced and bound briefly to an activator surface by either pathway, a cascade of enzymatic steps resulting in membrane insertion of the membrane attack complex C5b-C9 (MAC) occurs (Table 1). The MAC assembly has the shape of a grommet. One side is hydropho-bic, and it opens a physical hole through the target membrane. This allows for unregulated inflow of water and solute into the targets, causing potential hypotonic lysis of the target. Although this is clearly demonstrated to cause lysis of erythrocytes with in vitro complement assays and in some hemolytic anemias, the degree to which cytolysis contributes to cell death with nucleated cells is unclear. Cytoly-sis may be important in the host defense against certain encapsulated organisms, as deficiencies of the terminal complement components are associated with an increased incidence of infections with neisserial bacteria species. The noncytolytic, membrane-perturbing effects of MAC insertion may be more clinically relevant. For instance, insertion of a MAC into an endothelial cell causes endothe lial activation, possibly leading to irreversible cell injury not by lysis but by attraction of activated neutrophils.
Given the mechanisms and stimuli for complement activation, it is not surprising that the clinical sites of complement activation should coincide with sites of inflammation, such as sites of acute trauma and microbial invasion. Known possible activators at such sites would include, for the alternative pathway, microbes, denatured DNA and proteins released from cell death, and injured tissue with impaired protection against autologous complement fixation (see later discussion)—for the classical pathway, primarily microbes with antibody affixed and local antigen-antibody complexes, and for the lectin pathway, microbes, and, perhaps, perturbed cell membranes. In each case, C3a and C5a are released into the blood to attract leukocytes and capillary endothelium is rendered permeable.
Was this article helpful?
This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.