The goal of this investigation is to study directly (in situ) the immune interactions between N. gonorrhoeae and the human host. Gonococci are capable of causing different clinical manifestations of disease in different hosts. These include uncomplicated (often asymptomatic), locally invasive (e.g. pelvic inflammatory disease) and disseminated disease. Patients with these types of infection will be identified and carefully classified. In addition a group of women who are well defined secondary (spread) contacts of infected men will be identified to assess their risk of developing specific manifestations of gonococcal infection, particularly pelvic inflammatory disease. Gonococci will be captured directly from secretions of infected patients with monoclonal antibodies and examined for surface bound immunoglobulins and complement components by solid phase enzyme-linked immunosorbent assay (ELISA). In addition complement component proteins, and specific antibody activity directed against lipooligosaccharide (LOS) and outer membrane protein (OMP) antigens of infecting gonococci will be measured in secretions of infected patients by solid phase ELISA. The identification of host proteins on the surface of gonococci and the measurement and characterization of these proteins in the secretions will permit an assessment of the biologic mechanisms that operate in patients with different clinical manifestations of disease. This will provide an understanding of how individual hosts respond to gonococcal infection as well as how individual strains of gonococci cause unique manifestations of disease. These findings in secretions of infected patients will be interpreted in light of objective manifestions of infection and inflammation which will not only include the clinical manifestations but also measurements in secretions (by monoclonal antibody capture technique) of organism loads and the polymorphonuclear leukocyte response. Measurement of antibodies in serum directed against lipooligosaccharide (LOS) and outer membrane proteins (OMPs) plus functional antibody activity measured by complement dependent bactericidal activity and antibodies that block bactericidal activity will be employed to assess the role of systemic immunity in gonococcal diseases. These studies will also be performed in exposed but uninfected female contacts to identify possible mechanisms of protection that might be studied in populations at risk for acquiring different forms of gonorrhea.
Showing the most recent 10 out of 14 publications