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A C Wunderlich

Publications and source records attributed to A C Wunderlich.

9 recordsLinked to original sources

Specific cross-protective antigonococcal immunity in the murine genital tract.

Specific acquired immunity to gonococci was studied in systemically immunized mice, challenged with 10(7) gonococci by intrauterine inoculation. Protection after intraperitoneal immunization was monitored by vaginal cultures taken 24 h post-challenge, since events during the first 24 h postexposure to gonococci are crucial in determining the outcome of infection. Mice were protected against gonococcal challenge by two inoculations with either live or boiled gonococci given 4 weeks apart, whereas immunization with one inoculation did not protect against challenge 1 week later. Protection was correlated with high titers of IgG antibody in serum after two immunizations, but not with the high titers of serum IgM antibody found after the one immunization. IgG antibodies, but not IgM antibodies, were shown to pass into genital secretions. Protection could be passively transferred by serum with high titers of antibody. Of most practical importance was the finding that not only were heat-stable antigens protective, but also heterologous protection resulted after immunization with three strains differing in source (disseminated gonococcal infection versus gonorrhea), opacity-transparency characteristics, and serum sensitivity. The data indicate that IgG antibodies resulting from systemic immunization with heat-stable antigens may be able to provide cross-protection immunity against gonorrhea.

Animals↗

Effects of penicillinase on bactericidal and complement activities in normal human serum.

During routine addition of penicillinase (beta-lactamase) to patients sera, we found that the capacity of some of these sera to kill serum-sensitive gram-negative organisms was significantly decreased. Further controlled studies showed that penicillinase decreased both the bactericidal activity of normal human sera and the total hemolytic activity (CH50) of complement in these sera. The decreased bactericidal activity correlated significantly (r = 0.57, P less than 0.05) with the reduction of CH50 in eight normal sera. These effects of penicillinase were time and temperature dependent. Measurement of individual complement component activities showed that penicillinase decreased the activity of C2, C4, and C3-C9, suggesting that the penicillinase preparation activated the classical pathway. These results cast doubts on the validity of bactericidal determinations when sera are pretreated with penicillinase.

Bacteria↗

Natural immunity to murine gonococcal bacteremia: roles of complement, leucocytes, and sex.

The roles of the serum bactericidal system, inflammatory cells, and sex in resisting gonococcal infection were studied in a murine model of gonococcal bacteremia. The role of serum killing in defense was investigated with complement component 5 deficient (C5-deficient) (B1O.D2/OSN) and normal (B1O.D2/NSN) mice. No significant differences were found between LD50's with either murine serum-sensitive or serum-resistant gonococci in those two mouse strains. However, in vitro experiments revealed a heat-stable factor in mouse serum which killed gonococci. Thus it appeared that the C5-deficient mouse is not a good model for the study of the role of C-mediated killing in resistance to gonococcal infection. Mice with Chediak-Higashi disease were used to study the role of phagocytes and natural killer cells. The difference in LD50's between affected mice (C57B1/6J beige J) and controls (C57B1/6J) was significant. The CBA/N mice, which have a B-cell maturation defect, were no more resistant to infection than control mice, which was taken as further evidence that B cells were less important than other leucocytes in innate immunity to gonococcal infection. Finally, male mice were significantly more resistant than female mice to gonococcal bacteremia. Thus, in this study the two most important determinants of resistance to gonococcal infection were inflammatory cells and sex.

Animals↗

The role of C9 in complement-mediated killing of Neisseria.

During the routine examination of a healthy 31-yr-old woman, we found an incomplete deficiency of the 9th component of complement (C9). By hemolytic assay her serum C9 activity was 10 to 15% of normal. Limited family studies suggested that she inherited the deficiency as an autosomal codominant trait. She had no history of unusual or severe infections. When tested for bactericidal activity against serum-sensitive Neisseria gonorrhoeae and N. meningitidis, her serum reacted comparably to normal serum. Normal serum depleted immunochemically of C9 and sera from congenitally C9-deficient patients were also bactericidal against serum-sensitive Neisseria but required 120 min to kill the same numbers of gonococci that intact serum killed within 30 min. In the electron microscope, N. gonorrhoeae incubated with C9-depleted serum were fragmented but lacked the typical C lesions. Therefore, serum lacking C9 can kill serum-sensitive Neisseria, unlike sera deficient in the other terminal C components.

Adult↗

Role of magnesium in the enzyme-linked immunosorbent assay for lipopolysaccharides of rough Escherichia coli strain J5 and Neisseria gonorrhoeae.

An enzyme-linked immunosorbent assay for antibody to the lipopolysaccharides (LPSs) of a rough strain of Escherichia coli (J5) and Neisseria gonorrhoeae was developed. When standard methods of this assay were applied to these LPSs, no antibody was measured. By radiolabeling smooth and rough endotoxins with 51Cr, it was discovered that the rough LPS was not adhering to the polystyrene tubes. When Mg++ was added, however, all endotoxins absorbed to the solid phase. With this assay antiserum to core glycolipid had higher titers against its smooth parent strain than did homologous glycolipid had higher titers against its smooth parent strain that did homologous antiserum, and antisera to gonococci had high homologous but low heterologous titers. Thus, these data demonstrate that bulky O side chains do not hinder the penetration of antibody to core glycolipid and that LPSs from gonococci are heterogeneous but do cross-react.

Animals↗

Disseminated gonococcal infection in mice.

Gonococci do not readily cause disseminated infection in mice. To simulate some of the conditions leading to disseminated gonococcal infection in women, we suspended gonococci in mucin plus hemoglobin and studied the development of gonococcal bacteremia. The mucin-hemoglobin mixture was used because the menstruum appears to be involved in dissemination of gonococci from the genital tract during menstruation. Mice did not die after massive inocula of 10(9) gonococci given intraperitoneally in broth, but when gonococci were suspended in mucin (15%) alone, the 50% lethal dose was 10(8.4) and in 15% mucin plus 4% hemoglobin (M/H), the 50% lethal dose fell to 10(6.6). Sublethal doses produced local peritonitis and transient bacteremia. With larger inocula the local peritoneal infection progressed to fatal septicemia. Studies of the mechanism by which M/H lowered the 50% lethal dose showed that systemic clearance mechanisms were compromised, but not enough to account for the total decrease in the 50% lethal dose. If gonococci were given intravenously after intraperitoneal inoculation of M/H, sequestration of gonococci in the peritoneal cavity occurred, suggesting an effect on local peritoneal defenses. The effect on neutrophils appeared most significant, since numbers of neutrophils in the peritoneal fluid were decreased in the presence of M/H and neutrophils were destroyed by M/H in vitro. The serum bactericidal system was not affected. We conclude that M/H promotes gonococcal bacteremia by interference with phagocytosis and intracellular killing of gonococci. The model simulates the disseminated gonococcal infection cases in women which follow pelvic inflammatory disease in its progression from local peritonitis to transient or lethal bacteremia and in factors (mucin and hemoglobin) which enhance infection.

Animals↗

Common heat stable protective antigen in gonococci.

1. Gonococci possess a common heat stable antigen that is not identical to endotoxin. 2. A model of gonococcal peritonitis is described that simulates human disease in its progression from local to disseminated infection and its milieu of mucin and hemoglobin. 3. Vaccination with the heat stable antigen protected against disseminated infection and raised the LD50s from 100 to 1000-fold. 4. Vaccination with antigen from one strain of gonococci conferred protection against heterologous infection. 5. This protection did not require pili antigens or bactericidal antibody. 6. Protection in vaccinated mice resulted from a rapid, intense, and chemotactically-mediated influx of PMNs that eradicates the local infection.

Animals↗

Technique for transcervical intrauterine inoculation of the mouse.

Suspensions of india ink or gonococci were inoculated into the murine uterus through the cervix with a simple plastic vaginal speculum and a 23 gauge blunted needle. The inoculated suspensions were distributed throughout both uterine horns, cervix, and vagina, but did not flow into the peritoneal cavity. This method avoided surgical stress as well as being simple, fast, and reproducible.

Animals↗