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Biomedical subjects

V Wicher

Publications and source records attributed to V Wicher.

71 records · Page 4Linked to original sources

In vitro cell response of Treponema pallidum-infected rabbits. III. Impairment in production of lymphocyte mitogenic factor.

Production of mitogenic factor was examined in rabbits infected intratesticularly with T. pallidum and in control animals injected with saline or saline extract of normal rabbits' testes. Lymph nodes and spleen from animals killed 2, 6 and 12 weeks after injection were used as the source of lymphocytes, cultured in serum-free medium in the presence of Reiter antigen. The active supernatants of lymph node cells (LNAS) and spleen cells (SPAS) were examined for the presence of mitogenic factor using normal rabbit peripheral lymphocytes. The LNAS of control animals showed a mitogenic index (MI) between 4 and 6 and the infected animals less than 2. The SPAS of infected and control rabbits showed an MI of less than 2. The lower mitogenicity in LNAS of infected and that of SPAS of infected and control animals seems to be due to the presence of inhibitors of DNA synthesis.

Animals↗

In vitro cell response of Treponema pallidum-infected rabbits. I. Lymphocyte transformation.

Lymphocyte response to phytohaemagglutinin (PHA), Treponema pallidum, cultivable Reiter strain and cardiolipin reagent were examined using peripheral lymphocytes of T. pallidum-infected rabbits and control animals injected intratesticularly with saline extract of normal rabbit testes mixed with T. pallidum-free saline extract of infected testes. The response to PHA was significantly suppressed only in the infected animals, reaching the lowest level at 30 days after infection. A substantial increase of lymphocyte stimulation in the presence of cardiolipin reagent at 20 days after infection correlated well with the appearance of the maximum titre of Wassermann antibodies. Significant (P less than 0.02) increase in spontaneous response of cells incubated for 5 days made the response to T. pallidum and the Reiter strain difficult to interpret. An explanation for the spontaneous response is offered.

Animals↗

Host response to treponema pallidum infection. II. Rabbit leukocyte migration inhibition in the presence of homologous organ extracts.

Peripheral leukocytes of 67 rabbits infected intratesticularly with Treponema pallidum, Nichols' strain for various lengths of time were examined by the migration inhibition test for their response to extracts of normal rabbit heart, skin, brain and T. pallidum antigen. A control group of 14 animals injected intratesticularly with extract of normal rabbit tests was similarly examined for the leukocyte response to the same antigens except the brain extract. The percentage of infected animals responding to T. pallidum antigen with significant migration inhibition varied from 13 to 31. Transitional cellular response to heart and skin but not brain was observed (12-28%). Leukocytes of all but 2 control rabbits responded to the organ extracts within the limit of 2 SD. The response of the infected animals to the homologous organ extracts may suggest that during infection, lymphocytes are activated by the host tissue antigens.

Animals↗

In vitro cell response of Treponema pallidum-infected rabbits. II. Inhibition of lymphocyte response to phytohaemagglutinin by serum of T. pallidum-infected rabbits.

Serum inhibitors of lymphocyte response to PHA were found in T. pallidum-infected rabbits. The humoral inhibitors could be detected as early as 10 days after infection and persisted for at least 6 months. The factors also suppressed the allogeneic lymphocyte response. Control, or normal, rabbit sera likewise contain serum inhibitors, but in much lower concentration. The detection of the humoral inhibitors depended on the susceptibility of the indicator lymphocytes. Cells of some rabbits were more sensitive to the inhibitors than others. In addition to serum inhibitors, lymphocytes of T. pallidum-infected animals seem to be impaired and responded to PHA less vigorously than cells of normal rabbits. The inhibitory activity is most likely the result of a complex group of substances with different physicochemical characteristics; some pre-exist and others are newly formed after infection. Problems associated with the detection of such inhibitors are discussed.

Animals↗

Cellular and humoral immune response to guinea pig infected with Treponema pallidum.

Guinea pigs infected intradermally with Treponema pallidum Nichols strain were examined for the presence of lesions and for cellular and humoral response. Of the 26 guinea pigs (77%) demonstrated darkfield positive lesions between 6 and 20 days after infection. Animals divided into six groups of 4-5 in each were sacrificed between 2 and 24 weeks. The peritoneal exudate cells, obtained 4 days after injection of oil, were examined by the direct and the cells from lymphoid organs by the indirect capillary leukocyte migration method in the presence of 10 and 30 mug/ml of Reiter antigen. The peritoneal exudate cells responded with enhancement of leukocyte migration, reaching significant values between 6 and 24 weeks after injection. The cells from the lymphoid organs showed enhancement of leukocyte migration until the 4th week of infection. Treponemal antibodies, found in all animals, started to appear at the 4th week reaching a maximum titer at the 12th week after infection. The appearance of the antibodies correlated well (p less than 0.05) with the appearance of the enhancement of leukocyte migration. Wassermann antibodies were not detected throughout the 24 weeks of infection. The unique immune responses are discussed in view of the available data concerning natural acquired and experimental syphilis.

Animals↗

Cell response in rabbits infected with T. pallidum as measured by the leucocyte migration inhibition test.

Leucocyte migration in agarose was used to examine cell response in 48 rabbits infected with the Nichols strain of T. pallidum for 1 week to 16 months. The response of the peripheral leucocytes to T. pallidum antigen (TpAg), 3 and 15 mug/ml., Reiter antigen (RAg) 6 mug./ml., and VDRL reagent 1:500 was examined. The cells in the presence of RAg, TpAg--3 mug./ml.--and the VDRL reagent demonstrated a biphasic response; in the early stage of infection (until the 4th week) stimulation of leucocyte migration and in the later stage of disease inhibition of leucocyte migration was observed. The higher concentration of TpAg--15 mug./ml.--caused only inhibition of leucocyte migration. The leucocyte response in vitro could not be confirmed by intradermal skin tests with 5 x 10(7) heat-killed T. pallidum. No correlation between the cell response and the treponemal antibodies was observed.

Animals↗

Specificity of lymphocytotoxic antibodies in AIDS and pre-AIDS patients.

The number of T helper and T suppressor cells (determined with monoclonal antibodies) and the presence of serum lymphocytotoxic antibodies with T helper and T suppressor specificities were determined in 3 AIDS and 10 pre-AIDS patients and in 6 healthy homosexual and 17 healthy heterosexual controls. The 13 patients were 8 homosexuals and 5 drug addicts. Lymphocytotoxic antibodies were detected in all of the symptomatic individuals (AIDS and pre-AIDS) but in only 1 (6%) of the healthy heterosexual controls. Lymphocytotoxic antibodies in the patients ranged in titer from 125 to 625. The antibodies were detected at 15, 20, and 37 degrees C, but the reactivity at 37 degrees C was 20 to 40% lower than at 15 degrees C. All of the patients' antibodies reacted with both T helper and T suppressor cells, but in 9 sera the reaction was higher with the T helper and T (p less than 0.05). No correlation could be found between the patients' level of T helper lymphocytes or T helper/T suppressor cell ratios and their levels of lymphocytotoxic antibodies (p greater than 0.1). Sera of 7 patients and 3 of 9 healthy heterosexual controls reacted with non-T mononuclear cells (B cells plus monocytes). The degree of cytotoxicity with these cells did not correlate with the levels of lymphocytotoxic antibodies to T cells.

Acquired Immunodeficiency Syndrome↗

Biochemical, hematologic, and histopathologic studies in rabbits intrarectally inseminated.

Rabbits subjected three times a week for 7 months to administrations of fresh homologous semen, colonic enemas, or semen (previously frozen at -70 degrees) preceded by enema were monitored by a battery of biochemical and hematologic tests and histopathologic examination. No biochemical, hematologic or histopathologic changes were observed. Negative blood cultures and serum endotoxin determinations excluded any possibility of systemic bacterial infection caused or induced by the treatments. Wide temporary variations in the hematologic parameters, including concentrations of T and B cells, were observed in all treated groups. The relevance of these findings to immune status is not yet certain.

Animals↗

Alteration of immune response induced by chronic intrarectal insemination in rabbits.

Three groups of adult male Nya:(FG) rabbits were treated intrarectally, 3 times a week for 7 months, with 1 ml of fresh homologous semen, 20 ml of colonic enema, or 20 ml of enema followed by 1 ml of previously frozen semen. A control group was untreated. The results of several in vitro tests of humoral and cellular response showed that chronic intrarectal insemination leads to an abrogation of the immune response, expressed differently in the two groups of rabbits receiving semen. A consistently depressed blastogenic stimulation in response to T-cell mitogens was observed only in the animals receiving fresh semen. Neither group produced antilymphocyte antibodies. Anti-seminal-fluid and antispermatozoa antibodies were detected after 3 months of treatment in two animals receiving enema and semen and one animal receiving fresh semen. Circulating immune complexes were detected after 2 months of treatment in animals receiving enema and semen. These immune complexes contained predominantly IgM and were specific for seminal antigens. Assay of the cellular response to a T-cell-dependent antigen showed, in the animals receiving enema and semen, a pronounced decrease in the indirect IgA and IgG plaque-forming cells response with practically no effect on the IgM response. These results, taken together with those of the preceding paper, suggest that in intrarectally inseminated rabbits the functional capabilities of the immune system may deteriorate without histologic or morphologic changes in the anorectal mucosa of relevant lymphoid tissues.

Animals↗

Kinetics of antibody response to polypeptides of pathogenic and nonpathogenic treponemes in experimental syphilis.

Antigenic cross-reactivity between Treponema pallidum subspecies pallidum (TP) and nonpathogenic Treponema phagedenis biotype Reiter (TR), Treponema refringens strain Noguchi (TN), and Treponema vincentii (TV) was examined by the Western immunoblotting technique in pooled sera from five rabbits infected intratesticularly with T. pallidum. Sera were obtained before infection and on days 6, 12, 20, 30, 60, and 120 after infection. The pooled preinfection sera reacted with nine polypeptides of TV, nine of TS, and five of TR. The pooled sera did not show any clear-cut reactions with TP, but some individual rabbit sera did demonstrate visible reaction with three to five polypeptides of TP. Twelve days after infection, multiple serum antibodies reacting with polypeptides of all treponemes were detected. The number of antibodies reacting with polypeptides and the intensity of reaction increased with the duration of infection; for the nonpathogenic treponemes (TV, TS, TR) 21-26 polypeptides were identified on day 30, and by day 60 a total of 21 were detected for TP. By day 120 the reaction had become less pronounced, and fewer reactive polypeptides were seen. The extent of the cross-reactivity with the three nonpathogenic treponemes reflects the complex structure of T. pallidum, which should be viewed as a mosaic of more cross-reacting than strain- or species-specific antigens.

Animals↗