Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that pertussis toxin is a virulence factor of Bordetella pertussis. Although extracts enriched in pertussis toxin activity have been reported to enhance immune responsiveness, other studies have demonstrated a suppressive ability, suggesting that the toxin may contribute to the virulence of B. pertussis through mechanisms involving immune suppression. We report that purified pertussis toxin suppressed the in vitro immunoglobulin M antibody response of mouse splenocytes to sheep erythrocytes. At submitogenic doses, the toxin also suppressed [3H]thymidine incorporation by splenocytes, suggesting that it interfered with antibody formation by inhibiting lymphocyte proliferation. Antiviral activity was detected in culture supernatants obtained from pertussis toxin-suppressed splenocyte cultures by using a cytopathic effect inhibition assay. This antiviral activity was virus nonspecific, sensitive to pH 2.0 treatment, stable to heating at 56 degrees C, and neutralized by anti-gamma interferon antiserum. Finally, the fractionation of splenocytes by anti-immunoglobulin panning techniques suggested that Lyt2+ lymphocytes proliferated in response to pertussis toxin and produced interferon. Our results suggest that pertussis toxin may contribute to the virulence of B. pertussis through stimulation of Lyt2+ lymphocytes, resulting in the induction of gamma interferon and the subsequent inhibition of the primary antibody response.
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PMID:Immune suppression and induction of gamma interferon by pertussis toxin. 392 34

All vaccines have--besides their specific effect on the immune response--more or less pronounced side effects on the organism and particularly on the immune system. The latter effects deserve special interest, whenever they increase the host defence against infectious diseases. Desirable paraspecific effects of vaccines are the induction of interferon, the enhancement of phagocytic function and the activation of lysosomal enzymes. Some vaccines exert different effects: attenuated live measles vaccine induces interferon, pertussis vaccine activates lysosomal enzymes of macrophages. Some clinical observations illustrate how paraspecific effects of vaccines can be utilized for therapeutic purposes.
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PMID:[Unspecific vaccination]. 616 50

The ability of DTP (diphtheria, tetanus, pertussis) vaccine to stimulate IgG-plaque forming cells (PFC) in mice was markedly inhibited by human leukocyte and mouse fibroblast interferon (IF). This effect of IF was not dose-dependent. The maximum inhibitory effect of human IF was observed on Day 10 after the administration of the vaccine. The inhibition of IgM-PFC was more severe when human IF was used. Although IF abrogated the effect of DTP vaccine on IgG-PFC, at the same time it stimulated PFC in the control group of non-vaccinated animals. The administration of DTP vaccine decreased IgM-PFC on Day 5, the effect was enforced by the addition of both human and mouse IF. IF decreased IgM-PFC in the control group. Small and large doses of DTP suppressed the leukocyte adherance inhibition (LAI) on Day 5 after administration of the vaccine, the effect was not affected by addition of IF. The suppressive effect of DTP was lost on Day 10 when addition of IF increased the percent of LAI in all experimental groups. Thus IF appears to interfere with the effect of DTP and selectively modulate the different immune responses.
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PMID:Interferon as an in vitro modifier of immune responses induced by combined vaccine (DTP) in mice. 668 44

Several studies have demonstrated that Bordetella pertussis has the ability to enter and survive intracellularly within human polymorphonuclear leukocytes (PMNL) and human monocytes/macrophages. The effects of human recombinant gamma interferon (IFN-gamma) on the survival of B. pertussis in PMNL and human monocytes, and on the oxidative burst activity of PMNL and human monocytes in response to B. pertussis were assessed in this study. IFN-gamma partially increased intracellular killing of phagocytosed B. pertussis in human monocytes, as determined by an orange acridine-crystal violet assay. In contrast, IFN-gamma did not enhance intracellular killing of B. pertussis in PMNL. No significant increase of superoxide production was noted in human monocytes in response to B. pertussis when stimulated with various concentrations of IFN-gamma. The partial increase of B. pertussis killing by IFN-gamma within monocytes, together with poor production of superoxide may explain how B. pertussis can survive within human phagocytic cells, and thus cause a more prolonged course of the disease.
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PMID:Effects of recombinant human gamma interferon on intracellular survival of Bordetella pertussis in human phagocytic cells. 781 66

A murine respiratory challenge model was used to examine the induction of cellular and humoral immune responses and their role in protection against Bordetella pertussis following immunization or previous infection. Spleen cells from mice convalescing from a B. pertussis infection exhibited extensive in vitro T-cell proliferation and secreted high levels of interleukin-2 (IL-2) and gamma interferon but not IL-4 or IL-5, a cytokine profile typical of CD4+ Th1 cells. Serum from these mice had low or undetectable anti-B. pertussis antibody levels. In contrast, mice immunized with an acellular pertussis vaccine had high levels of B. pertussis antibodies and spleen cells secreting IL-5 but not gamma interferon, a profile characteristic of CD4+ Th2 cells. Immunization with an inactivated whole-cell vaccine induced both CD4+ Th1 and serum antibody responses. After exposure to a B. pertussis respiratory challenge, the convalescent mice and those immunized with the whole-cell vaccine eliminated the bacterial infection significantly faster than mice immunized with the acellular vaccine. These findings show that the selection of antigens and their form of presentation are important in determining whether the subsequent immune response is cellular, mediated by Th1 cells, or humoral, mediated by Th2 cells. In the murine model, the induction of a Th1-mediated cellular immune response appears to be a key element in acquired immunity to a B. pertussis infection.
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PMID:Effective immunization against Bordetella pertussis respiratory infection in mice is dependent on induction of cell-mediated immunity. 833 49

Administration of pertussis toxin (PT) in combination with diphtheria and tetanus toxoids adsorbed (DT vaccine) or with acellular pertussis vaccine adsorbed and diphtheria and tetanus toxoids (APDT) elicits dose- and time-dependent alterations in hepatic drug metabolism in mice. Cytochrome P-450 (P-450) levels were inhibited more than 50% at 7 days following a single injection of PT mixed with either vaccine. When combined with DT vaccine, 125 ng of PT was required to produce this effect, while as little as 16 ng of PT combined with APDT vaccine inhibited P-450 levels. The inhibition of P-450 levels is similar to that observed after a single injection of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP). Alterations of P-450 levels were accompanied by increased activities of quinone reductase but not with changes in plasma interleukin-6 or tumor necrosis factor levels. Other Bordetella pertussis virulence factors, such as filamentous hemagglutinin, fimbriae and pertactin, were also tested but had no significant effect on hepatic drug metabolism. Endotoxin or preparations containing endotoxin caused alterations in hepatic drug metabolism within 24 h, concomitant with increased interleukin-6 and tumor necrosis factor levels, but these effects had resolved by 1 week. DTP vaccine and preparations containing PT caused a marked induction of gamma interferon coincident with the maximal inhibition of P-450 levels. This effect was not present with DT or APDT vaccine alone, nor with endotoxin or any combination of factors that did not contain PT. These results demonstrate that PT is a necessary component for the sustained effects of DTP vaccine on hepatic drug metabolism and suggest a role for gamma interferon in this process.
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PMID:Pertussis toxin-induced alterations of murine hepatic drug metabolism following administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed. 840 12

A murine respiratory infection model was used to study the mechanism of protective immunity to Bordetella pertussis. We found that nude mice, which are deficient in T cells, developed a persistent infection and failed to clear the bacteria after aerosol inoculation. In contrast, normal adult nonimmune mice cleared a respiratory infection approximately 35 days after challenge. Before bacterial clearance, antipertussis antibody levels in serum were low or undetectable, whereas consistent antigen-specific T-cell responses were demonstrated throughout the course of infection. The in vitro responses detected in immune spleen cells were mediated by a population of CD4+ major histocompatibility complex class II-restricted Th1-like cells that secreted interleukin-2 and gamma interferon but not interleukin-4. Adoptive transfer of immune spleen cells into nude or sublethally irradiated immunosuppressed mice before challenge resulted in bacterial clearance within 14 to 21 days. In contrast, injection of serum from convalescent mice before challenge only marginally reduced the bacterial load early in the course of infection. Furthermore, transfer of enriched T cells or purified CD4+ T cells but not CD8+ T cells from immune mice conferred a high level of protection. Recipients of CD4+ T cells cleared the bacteria from the lungs within 20 days of challenge, at which time B. pertussis-specific antibodies in the serum were undetectable. Although we do not rule out a contribution of mucosal immunoglobulin A, our findings suggest that cellular responses mediated by CD4+ Th1 cells play an important role in protective immunity to B. pertussis.
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PMID:Cell-mediated immunity to Bordetella pertussis: role of Th1 cells in bacterial clearance in a murine respiratory infection model. 842 70

The adherence of Bordetella pertussis to respiratory cilia and its survival in neutrophils and macrophages is crucial to the pathogenesis of whooping cough. To investigate the role of endogenous interferon (IFN)-gamma in acute infection, levels of IFN-gamma in bronchoalveolar lavage (BAL) fluid of mice infected intranasally with B. pertussis were determined. Since pertussis toxin is released during infection by B. pertussis either locally or systemically, serum levels of IFN-gamma in mice injected intravenously with pertussis toxin were also determined. A persistent and significant increase of IFN-gamma levels with concomitant peripheral blood lymphocytosis was observed after 5 and 10 days. The results of this study showed an early but transitory production of endogenous IFN-gamma in BAL fluid of mice infected with B. pertussis.
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PMID:Interferon-gamma levels in serum and bronchoalveolar lavage fluid of mice infected with Bordetella pertussis. 844 Sep 45

We examined the major pathogenic substances of Bordetella pertussis for the ability to induce nitric oxide, and important biological function of macrophages, via gamma interferon in spleen cells. B. pertussis, which produces a variety of pathogenic substances, including pertussis toxin and filamentous hemagglutinin, causes a severe respiratory disease. Nitric oxide was detected in the culture fluid of spleen cells stimulated with pertussis toxin or its B oligomer but not in the culture fluid of spleen cells stimulated with the A protomer of pertussis toxin or with filamentous hemagglutinin. Incubation of the peritoneal exudate macrophages with pertussis toxin, B oligomer, A protomer, or filamentous hemagglutinin induced little nitric oxide, whereas incubation with gamma interferon induced a significant amount of nitric oxide. The induction of nitric oxide in spleen cells stimulated with pertussis toxin was completely inhibited by anti-gamma interferon antibody. The treatment of spleen cells with anti-Thy-1.2 antibody plus complement followed by stimulation with pertussis toxin decreased the secretion of gamma interferon and nitric oxide. These results suggest that gamma interferon from T lymphocytes stimulated with pertussis toxin induces nitric oxide.
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PMID:Nitric oxide induction by pertussis toxin in mouse spleen cells via gamma interferon. 860 94

The recombinant cytokines interferon (IFN)-gamma and interleukin (IL)-12 stimulate several macrophage-mediated functions that are important in host defense. An experimental pertussis model showed that intraperitoneal (i.p.) administration of 10,000 U of recombinant murine (rm) IFN-gamma to mice at the time of Bordetella pertussis infection caused a marked and significant reduction in the number of colony-forming units of bacteria in the lungs. Administration i.p. of 1 microgram of rmIL-12 or 1 microgram of rmIL-12 at the time of and for 5 consecutive days after B. pertussis challenge also induced a significant reduction in the number. However, i.p. administration of 1 microgram of rmIL-12 with 10,000 U of IFN-gamma at the time of B. pertussis challenge did not provide protection. These findings indicate that exogenous administration of rmIL-12 and rmIFN-gamma enhances resistance of mice to B. pertussis infection.
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PMID:Effects of recombinant murine (rm) interleukin-12 and rm interferon-gamma in mice infected with Bordetella pertussis. 884 17


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