Natural defense mechanisms in clinical sepsis

Abstract

Although the importance of both cellular and humoral mechanisms of defense against infection have been known since the turn of the century, they did not receive their deserved attention for many years because of inadequate techniques for studying these important and complex processes. Interest in basic host mechanisms was rekindled by the description of a case of agammaglobulinemia by Colonel Ogden Bruton in 1952, and much has been learned about the basic concepts of immune defense since that time. An attempt has been made in this discussion to summarize the more important of these discoveries. By no means have all of the questions been answered, but the relatively new tools for investigation of subcellular and biochemical events promise to unfold a new era in the study and treatment of clinical sepsis in the near future. Current knowledge allows the surgeon to view the infective process as a continuum from the initial inflammatory response to generalized sepsis. The basic mechanisms of host defense are essentially similar for all types of infection. These include the closely interrelated and interdependent processes in the development of an inflammatory lesion with the delivery of opsonic substances and competent phagocytic cells from the circulation. Specific antibody in concert with complement alters the surface membranes of bacteria, rendering them more attractive to the phagocytic cell. Once phagocytosis has occurred, the bacteria are usually killed by a process of intracellular digestion. This basic sequence of events may be interrupted at any level as a result of a relative or absolute malfunctioning of the system. Of greatest importance in the development of clinical sepsis are those conditions which inhibit the delivery of phagocytic cells to an infective focus, the lack of specific antibody, and abnormalities of the phagocytic cells. Therapeutic manipulations of a patient may adversely affect any or all of the basic host defense mechanisms. A clear understanding of the relationship between the critical inoculum of bacteria and the various components of host defense will aid the surgeon in the prevention and treatment of these all too frequent complications.