Endometrial complement: Physiology and pathophysiology

The complement system is an evolutionarily ancient facet of the human immune system that plays a profound and pleiotropic role in the immune response. Complement was among the first immune system components described by the first experimental immunologists, working in the late 19th century. The most important contributor to complement’s discovery and characterization was Jules Bordet, whose work on the two major components of humoral immunity led to the Nobel Prize in 1919.1 Bordet described two distinct components of animal serum responsible for bacterial cell wall rupture.2,3 The two serum components differed as to whether they maintained function after heating and whether prior antigen exposure was necessary. The first component, later termed antibodies, was heat resistant and was found only in animals with previous exposure to the same pathogen. A second component, originally termed ‘alexin’ was shown to be distinct from antibodies since it was heat-labile and was found in all animals, regardless of prior pathogen exposure. Alexin was later renamed ‘complement’ by Paul Ehrlich, because it ‘complemented’ the action of antibodies. It would be decades later before a primary action of complement directly on cell membranes would be experimentally described, although Baumgartner proposed direct membrane action, without evidence, as early as 1919.2,3 Experimental observations during the last 50 years have revealed a multitude of functions for the complement components in both humoral and cellular components of both innate and adaptive immune responses. It is now understood that complement factors play key roles in direct and antibody-mediated killing of pathogens and abnormal host cells, promotion of phagocytosis, mediation of inflammation, enhancement of humoral immunity, modulation of T-cell immunity, alteration of cytokine production, stimulation of specific immune cell proliferation, and regulation of immune tolerance.4 The complement system is also involved in the pathogenesis of ischemic, inflammatory, and autoimmune diseases.5,6 If uncontrolled, complement can lead to systemic inflammation, tissue destruction, and shock.7 Because the complement system is involved in so many processes and because unregulated complement activation can be lethal, a complex network of regulatory mechanisms exist that limit activation of complement proteins.

Duke Scholars

Author Steven L Young Obstetrics and Gynecology, Reproductive Endocrinology & Fert ...