SERUM FACTORS AND POLYMORPHONUCLEAR LEUKOCYTES IN HUMAN HOST DEFENSE AGAINST NEISSERIA-MENINGITIDIS - STUDIES OF INTERACTIONS WITH SPECIAL REFERENCE TO A CHEMILUMINOMETRIC TECHNIQUE

Luminol enhanced chemiluminescence (CL) was used to study the interactions of various serogroups of opsonized or nonopsonized meningococci (MC) with polymorphonuclear leukocytes (PMNL), and the results were compared with those of functional (serum bactericidal activity = SBA, phagocytic killing = PK) and nonfunctional (EIA and IFL) antibody tests. The inherent problems of inter-assay and day-to-day variations of the CL technique were solved by indexing the responses with the use of an international serogroup X reference MC strain (NCTC 10790). When opsonized with serum from healthy adults without a history of meningococcal (MC) disease, the pathogenic MC strains of serogroups A, B, C, Y (Orebro variant) and W-135 gave significantly lower CL indexes than the apathogenic ones of serogroups Y, Z, and 29E and of nongroupable strains (p<0.001). The same patterns were obtained when the strains were opsonized with serum from Swedish children 1-3 years old and also with serum from Sudanese children. Higher levels of antibodies against MC serogroup A polysaccharide were found in sera from Sudanese children than in those of Swedish ones. Correspondingly, the CL indexes for MC of serogroup A were somewhat higher for the Sudanese children than for the Swedish ones. In spite of this an MC epidemic due to a serogroup A strain could not be avoided in Sudan, but could in Sweden, where the same strain was introduced, indicating that other factors than serum immunity are of importance for avoidance of an MC serogroup A epidemic. In various series of experiments it was shown that the CL technique, like the SBA and PK tests, can discriminate between functional and nonfunctional antibodies in healthy individuals, in patients during and after MC disease and before and after vaccination, whereas EIA and IFL tests cannot. It was also shown that in the presence of serum from healthy individuals without a history of MC disease, both the classical and alternative complement pathways are activated to kill or to induce phagocytosis of apathogenic MC, whereas only the classical pathway is activated for the pathogenic ones. In the presence of serum from an individual vaccinated with MC capsular polysaccharide vaccine (high levels of anti-MC capsular polysaccharide antibodies), the pathogenic MC activate both the classical and alternative complement pathways for induction of phagocytosis. It is concluded that the standardized CL indexing technique for pathogenic and apathogenic MC has several advantages over the laborious and cumbersome SBA and PK assays in demonstrating and measuring the presence of functional anti-MC antibodies. It also has the capacity to discriminate pathogenic from apathogenic MC, and under certain circumstances it might be used as a diagnostic tool.