Intradermal infection of rabbits with Treponema pallidum imitiates rapid and active cellular response at the site of injection. During the first 2 weeks following infection, there is a marked increase in the numbers of organisms at the site of infection. Systemic dissemination of treponemes occurs during the early stage of infection, presumably before the immune response is fully mobilized. The mononuclear infiltration, which is apparent at the lesion site one week postinfection, becomes more pronounced at 2 weeks. The infiltrating cells are predominantly T lymphocytes and macrophages. By 4 weeks postinfection, most of the organisms have been cleared from the primary site; however, low numbers of treponemes survive locally and in distant tissues. Thus, whereas infection with T. pallidum appears to activate immune mechanisms which are capable of clearing most of the organisms from the primary lesion, some organisms are able to evade these mechanisms and persist in vivo.
ranging from 1 to 7 weeks of age. Five-week-old (31-36 days) neonates demonstrated waning resistance by the appearance of typically ulcerative, progressive lesions, though their parameters (duration, size) were not yet those of adult control lesions. The resistance demonstrated by neonates may be due in part to group housing (nesting) which could create unfavorable temperatures for T. pallidum survival; comparison of lesion development between nesting and individually housed neonates, 31 to 46 days of age, revealed a greater percentage of typical lesions developing among those individually housed (95 versus 52%). However, these differences may reflect the variability of typical lesion develop ment found among animals of this age when resistance begins to wane. In both groups, the duration of typical lesions was significantly shorter than for adult controls. A heat-stable serum factor(~) was demonstrated in 19 of 20 basal sera from neonates 4 to 6 days of age; this presented another possible mechanism of resistance. The neutralizing serum factor(s) was not demonstrable in the sera of does either before mating, during gestation, or shortly after kindling. The relationship of temperature, serum 1 966 GAMBOA AND MILLER factors, and nutritional factors to neonatal resistance following infection, which begins to subside as the animal reaches 5 weeks intradermal inoculation with T. pallidurn is discussed.of age. The potential influences of nesting and serum neutralizing factors upon resistance are advanced. Abbreviations W R L , Venereal Disease Research Laboratory NRS, nonimmune rabbit serum IRS, immune rabbit serum Micro-NZ, microneutralizationThe advent of penicillin therapy brought about a dramatic reduction in the incidence of congenital syphilis (12,34,39). However, the decline in both the use of routine screening procedures and physicians' training programs has resulted in the reemergence ofthis form of the disease as a public health problem (2, l I, 34, 38, 46, 49, 50, 60). Despite this problem, little is known about the interacting events associated with the organism and host which determine infectivity. Since the recognition of congenital syphilis as a distinct clinical entity, it has been generally accepted that treponemes cross the placenta only after the 4th month of gestation, at a time when the Langhans cell layer (cytotrophoblast) becomes atrophied (20). Recent evidence, however, indicates that treponemes can be found in conceptus material obtained during the first trimester (21). Silverstein and Lukes (43) and Silverstein (42) have suggested that infection during early gestation may go undetected due to the absence of an inflammatory reaction attributed to the immaturity of the fetal immune system. The introduction of Treponerna pallidurn from an infected mother to fetus may result in either a fulminating fatal disease, latency, or the absence of infection; factors which influence the outcome are not understood. The lack of a satisfactory and reproducible experimental rabbit model has precluded stud...
The immunological competence of neonatal rabbits inoculated intradermally with Treponerna pallidurn was examined. Both cellular responses and the production of humoral antibody to specific T. pallidurn antigens and to nonspecific antigens or mitogens were investigated. In blast transformation assays, splenic and popliteal lymph node lymphocytes from neonates inoculated with virulent T. pallidurn responsed to T. pallidurn antigens in a manner similar to or greater than inoculated adult rabbits. Splenic and popliteal lymph node lymphocytes from both uninoculated and T. pallidurn-inoculated neonate and adult animals showed consistent and similar responses to concanavalin A. Both neonate and adult animals inoculated with heat-killed T. pallidurn also responded but to a significantly lesser degree. Immunofluorescent examination of skin sections from the site of inoculation of adult and neonatal animals revealed 1) that the early infiltrate was composed predominntly of T cells, 2) diffuse antibody staining with rare B cells, and 3) fewer treponemes with significant fragmentation in neonates as compared to adult controls. Antibody production by neonates inoculated with virulent T. pallidurn was delayed 4 to 6 weeks postinoculation as measured by the fluorescent Treponemal antibody absorption and Venereal Disease Research Laboratory (VDRL) test procedures, respectively. Antibody was not detected among neonates inoculated with heat-killed treponemes during a 6-week observation period and only low levels of VDRL antibody were detected in a few adult control animals. Evidence for incomplete resistance of neonatal rabbits to the intradermal inoculation of Treponerna pallidurn was provided. Twenty-two of 23 neonatal rabbits resistant to symptomatic infection upon initial inoculation with treponemes were also resistant to homologous challenge 3 to 5 months later, thus indicating a refractive state. Additional evidence was provided by the appearance of generalized lesions among seven of 29 neonates.
Studies on group B beta-hemolytic streptococcus. 11. EffTetts on pulmonary hemodynamin and vascular permeability in unanesthetized sheep. Pediatr Res 15399 32. Romrnero TE, Friedman WF 1979 Limited left ventricular response to volume overload in the neonatal period: a comparative study with the adult animal.
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