Cellular immune responses during gonococcal and meningococcal infections.

The genus Neisseria contains two species of clinical importance: Neisseria gonorrhoeae and Neisseria meningitidis. Although these two microorganisms are closely related genetically, the diseases they produce differ greatly. N. gonorrhoeae is the etiologic agent of gonorrhea, currently among the most common of the classical sexually transmitted diseases, whereas N. meningitidis is the causative agent of meningococcal meningitis. Although these Neisseria species have been known for over a century and there are effective antibiotic therapies for both of these diseases, the morbidity and mortality associated with them remain significant. For example, the pediatric mortality of meningococcal infection places it among the top 10 leading causes of death of children in North America. Similarly, the number of cases of gonorrhea reported to the Centers for Disease Control has averaged about three-quarters of a million per year for the past several years. Despite a number of studies, the immunological mechanisms responsible for providing antigonococcal protection have been completely elucidated. In part, this is due to the lack of an animal model for studying gonococcal infection. Equally important, however, is the fact that most studies have concentrated on the systemic immune response to gonococcal infection (19, 25, 32, 37, 38), whereas the initiation of the infection occurs locally in a site apparently isolated from these circulating immune modalities. Thus, to completely understand antigonococcal immunity, it is necessary to study the local immune responses available at or near mucosal surfaces in the male and female reproductive tracts. Serum antibodies specific for a variety of surface antigens have been described in both meningococcal and gonococcal infections, and in some cases the presence of these antibodies can be correlated with resistance to infection. It has been proposed that these antibodies could be involved in complement-mediated bacteriolysis or opsonization of the microorganisms or both. Although these mechanisms may be important in providing systemic immunity, sites where the Neisseria spp. are commonly found (the nasopharynx and reproductive tract) are sparsely populated with phagocytes and are deficient in many of the components of complement. Recently, an increasing number of reports suggest that beside macrophage-dependent activities, cell-mediated responses such as cytotoxic T lymphocytes, natural killer (NK) cells, and antibody-dependent cell-mediated cytotoxicity (ADCC) might also have a role in the host defense against bacterial infection. A number of bacteria, including both gonococci and meningococci, make initial contact with the host at the mucosal level. It would follow that immunosurveillance mechanisms should be especially active at these anatomical sites. It is striking that large granular lymphocytes, the main effector cells ofNK cell activity and ADCC,