Basic Science Review : Nonspecific Resistance to Infection

Abstract

0 UR interest in nonspecific resistance to infection was stimulated several years ago by an intriguing accident. At that time we were studying the variety of serological reactions which are elicited by staphylococcal infections.ilre were adding an extract of the supernatant of a staphylococcal culture to human red blood cells, in order to see whether this would render them agglutinable by serum which contained staphylococcal antibodies. We waned to learn whether this extract was antigenie, and so planned a simple experiment. A group of mice were to be given the extract. Two weeks later, when they might have been expected to have produced antibodies, they were to be challenged with a lethal number of staphylococci. The extract was given, but by error the animals were challenged after only 20 hours-rather than two weeks. This was too soon for significant antibody production. Nfost of the control animals died-but, to our amazement, most of the mice receiving the extract survived! (When the experiment was subsequently done as originally planned, the extract failed to protect.) This accidental observation started us off on several years of work, the results of which shall be summarized later. It is sufficient to note here that this staphylococcal extract proved to have a nonspecific effect. Among other qualities it also protected mice against infection with E. coli and with Herpes simplex virus.Resistance to infection is all too often equated with specific antibodies. Yet we know very well that this is not the whole story.Resistance is the resultant of many factors in addition to antibodies. It has to do with the state of the infecting t~~ent as well as that of the host.The first part of this discussion will be a review of some of the resistance factors of the host which are nonspecific. These represent his first line of defense against infection. Many that we recognize, we do not fully understand. At any one time, relatively few may be operating. Their effect, often difficult to quantitate, is usually of much smaller magnitude than that of specific antibody. Yet, the fifth edition of &dquo;Principles of Bacteriology and Immunity&dquo; by Topley and Wilson devotes the greater part of at least six chapters to factors involved in nonspecific resistance to infection: &dquo;It is important to realize that were such (nonspecific) procedures applicable for prophylaxis or therapy (in man) their relatively small effect would not necessarily rule them out as unrewarding. A 10-fold increase of the LD 50 of a test bacterium in the experimental animal might well correspond in the field to a decrease of 20 to 40 per cent in the mortality or morbidity rates.&dquo; 2The second part of this discussion will have to do with some of our experience with our staphylococcal extract. It will show that there now are procedures available with which it is possible to enhance nonspecific resistance to infection-at least in mice and rabbits.