Humoral factors in host defense against microbial invaders

Normal host defense against microbial invaders depends upon an intact humoral and cellular system of inflammation and specific immunity. The major weapons for killing microbes that invade tissue are phagocytic cells, however, humoral factors enable these phagocytic cells to recognize, migrate toward, efficiently ingest, and kill the invaders. Humoral factors essential for host defense include specific antimicrobial immunoglobulin antibodies and multiple proteins which comprise the complement system. The complement system is the oldest phylogenetically and the most important protein in this system is C3. When C3 is activated on the surface of the microbe, ligan is formed which provides a firm bond between organisms and phagocytic cells. This process is termed opsonization and activated C3/C3b is a highly efficient opsonin. C3b attachment stimulates efficient engulfment by phagocytic cells and most microbes are rapidly killed once they are ingested. Complement may also function as a direct bactericidal factor when associated with specific antibody on the bacterial surface. Neisseria meningitidis and Neisseria gonorrheae are susceptible to this action of complement which requires participation of the terminal proteins of the system C6, 7, 8, and 9. Patients without these terminal components, therefore, are susceptible to systemic infections with Neisseria. Septicemia from Streptococcus pneumoniae and other encapsulated microbial species occurs with greatly increased frequency in patients without spleens. Complement and other as yet unidentified humoral factors which contribute to host defense against microbial invaders appear to be deficient in patients without spleens. Antimicrobial antibodies produced in response to antigenic stimulation by microbes are also essential humoral factors. Effective levels of antimicrobial antibodies develop only after microbes have colonized their host and the immune system has been stimulated and protection is delayed. Once produced, however, specific antibodies are potent opsonins and are effective activators of complement. Highly effective and efficient host defense is present when there are circulating specific antibacterial antibodies and an intact complement system. Septicemia may occur when there is a traumatic portal or entry of an exceptionally large bacterial challenge, however, deficiency of humoral or cellular factors of host defense is frequently involved in the pathogenesis of septicemia. Measures for preventing septicemia in susceptible persons include active immunization with microbial antigens or passive therapy with specific antimicrobial antibodies.