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)

Heat-labile, rat skin-fixing antibodies were detected readily in the sera of young female mice dosed intranasally with the body fluid of Ascaris suum (ABF) and the adjuvant, Bordetella pertussis vaccine (BPV). In addition, washed cell suspensions prepared from spleen and the lymph nodes regional to the lungs were positive in an adoptive cutaneous anaphylaxis assay, an assay which may detect activities of reagins associated with mast cells rather than reaginic antibody-secreting cells. The intraperitoneal route was a poor means of inducing circulating anti-ABF reagins and an intraperitoneal injection of ABF + BPV delayed the appearance of circulating reagins in mice dosed at the same time with ABF + BPV intranasally. Hypothymic female BALB/c. nu/nu ('nude') mice failed to produce circulating reagins to ABF but an injection of normal thymocytes or cortisone-resistant thymocytes from syngeneic female mice led to higher titers of circulating reagins than found in normal female BALB/c. nu/+ littermates. Using cells from young male or female syngeneic donors and male and female BALB/c. nu/mu recpiients, evidence was obtained for a defect in the thymus of young male mice and conceivably this defect may extend to the peripheral T cell population in such mice. Cyclophosphamide pretreatment or adrenalectomy increased circulating reagin titers in normal mice dosed intranasally with ABF + BPV, and pretreatment with lipopolysaccharide intranasally markedly reduced titers of circulating anti-ABF reagins. In the discussion, emphasis is given to the hypothesis that potent allergens are T cell-stimulating, relatively persistent antigens which, when located in submucosal lymphoid sites and under conditions of limited antibody production as a result of limited recruitment of 'helper' T cells systemically, lead to the induction and sustained production of IgE by resident Bxi cells and their progeny.
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PMID:Studies on immune responses to parasite antigens in mice. II. Aspects of the T cell dependence of circulating reagin production to Ascaris suum antigens. 108 24

Pertussis toxin (Ptx), an important adjuvant for inducing certain organ-specific autoimmune diseases in mice, exerts multiple effects upon the immune system. In addition to its adjuvant effects, which include enhancement of delayed-type hypersensitivity and increased antibody production. Ptx elicits a marked lymphocytosis with a concomitant decrease in thymic weight. In vitro studies indicate that Ptx acts directly on thymocytes and that both susceptible and resistant populations exist. It is believed that these susceptible cells are released into the circulation and account, in part, for the T cell component of the lymphocytosis. We have used flow cytometry to analyze the CD4, CD8, and Thy-1 phenotypes of thymic and peripheral T cells from Ptx-treated mice. In the thymus, there is a dramatic decrease in the number of CD4+CD8+ (double positive) cells at all doses tested (0.25, 0.50, and 1.0 microgram) by day 4 after Ptx treatment. The double negative and single positive populations remain relatively constant. Analysis of Thy-1 expression reveals a significant reduction in Thy-1hi thymocytes, with little change in the Thy-1lo population. Thus Ptx primarily affects and depletes, in a dose-dependent fashion, thymic T cells with an immature phenotype. These results mimic those of corticosteroids, although neither prior adrenalectomy nor treatment with the antiglucocorticoid RU486 are able to prevent the effects of Ptx. In the periphery of Ptx-treated animals, the relative increase in the number of CD4+ T cells is more than that of CD8+ T cells. Double positive and Thy-1hi cells cannot be detected in appreciable numbers. These results are consistent with the concept that Ptx may drive immature thymocytes through accelerated maturation for release into the periphery as single positive, predominantly CD4+, Thy-1lo cells. Increased numbers of such cells may in part account for the immunopotentiating effects of Ptx, particularly as they relate to the induction of organ-specific autoimmune disease. Treatment with purified Ptx beta-oligomer fails to elicit any of the responses described above, indicating that the holotoxin is required for such activities.
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PMID:Pertussis toxin-induced lymphocytosis is associated with alterations in thymocyte subpopulations. 134 51

Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent delta cya delta crp delta asd S. typhimurium chi 3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, delta asd E. coli chi 6097, and S. typhimurium chi 3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi 3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild-type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197.
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PMID:Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium. 144 40

Although it is well known that essentially all peripheral T cells are derived from bone marrow progenitors that mature in the thymus, the mechanism whereby thymocytes gain access to peripheral compartments is obscure. We have learned that this process is sensitive to pertussis toxin (PT). Transgenic lck-PT mice were generated which express the catalytic subunit of PT in all thymocytes. In a previous study we observed that T cell receptor signaling is unimpaired in these cells despite the virtual elimination of their Gi protein signal transduction elements through endogenous PT activity. Here we demonstrate that mature T lineage cells accumulate in lck-PT thymuses and fail to populate peripheral lymphoid organs. The accumulating cells closely resemble normal peripheral T lymphocytes with respect to cell surface phenotype and responses to allogeneic spleen cells, yet perform poorly in in vivo homing assays. This migratory defect does not result from deficient expression of common homing receptors or alterations in intracellular cAMP concentrations. Based on these results, we propose that a novel PT-sensitive signaling pathway, almost certainly involving a Gi protein, is required for thymocyte emigration.
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PMID:A pertussis toxin-sensitive process controls thymocyte emigration. 165 69

Pertussis toxin is known to elicit lymphocytosis in whooping cough patients and experimental animals, by blocking the extravasation of lymphocytes and stimulating their release from lymphoid organs such as the thymus. The mechanisms responsible for these unique effects of PT are not fully understood. The effect of pertussis toxin (PT) on the invasive behavior of human CCRF-CEM T lymphoma cells has been investigated with the use of a monolayer invasion assay (MIA). We had previously found that invasion of murine T lymphoma cells in this model system was correlated with their ability to extravasate and form metastases after i.v. injection in syngeneic animals. We now show that human CEM cells can also penetrate through a precultured confluent monolayer of murine 10T1/2 fibroblast-like cells within a few hours. In a quantitative MIA run over 24 h, PT at concentrations above 10(-14) M inhibited invasion of the CEM cells. In addition, PT stimulated the release ('evasion') of CEM cells that had invaded under the monolayer before the toxin was added. The A subunit of PT was totally inactive, the B subunit had a small residual effect, and reconstitution of the AB complex partially restored the activity. The invasion-inhibiting activity of two different holotoxin preparations and of the subunits perfectly matched their activity in the Chinese hamster ovary cell clustering assay, which is known to depend on a functional AB complex. We suggest that inhibition of monolayer invasion by PT can be used as an in vitro model system to investigate the cellular and molecular mechanisms underlying the lymphocytosis-promoting action of the toxin. Furthermore, the method is sufficiently sensitive to be used for titration of toxin activity. Our data indicate that the ADP-ribosylating activity of the A subunit is indeed required, and that the promotion of lymphocytosis is not elicited by the binding of the B subunit alone.
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PMID:The lymphocytosis promoting action of pertussis toxin can be mimicked in vitro. Holotoxin but not the B subunit inhibits invasion of human T lymphoma cells through fibroblast monolayers. 196 Apr 20

Following the immunization of BALB/c mice with B. pertussis toxin, monoclonal antibodies (McAb) to the antigens of human epithelium, both dermal (the basal, superbasal or all epidermis levels) and thymic (the epithelium of the medullary zone, the cortical and medullary epithelium around Hassall's corpuscles), have been obtained. McAb have been obtained as the result of the polyclonal activation of autoreactive B-cells with B. pertussis toxin. McAb thus obtained can be used for the determination of the corresponding antigens in the epithelial tissues of the thymus and other organs in man, as well as for the diagnosis of tumors, histogenetically related to integumentary tissues of the epidermal genesis.
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PMID:[Synthesis of monoclonal antibodies to tissue-specific antigens of human skin and thymus epithelium in polyclonal activation by pertussis toxin]. 244 Feb 4

Lines of thymus-derived lymphocytes reactive against bovine myelin basic protein (BP) were established in vitro from SJL/J mice. These lines are stable in long-term culture and mediate inflammatory central nervous system (CNS) lesions and a low incidence of clinical experimental allergic encephalomyelitis (EAE) when injected into recipient SJL/J mice. The line cells proliferate in response to BP of bovine, rat, or mouse origin. Clones were derived from these lines, and the characteristics of these clones were analyzed. The clones express Thy-1, Ly-1, and L3T4 antigens and are negative for Ly-T2. The clones all proliferate in response to bovine BP, with different clones showing varying degrees of cross-reactivity between bovine, rat, and mouse BP. The proliferative response is MHC-restricted; antigen-presenting cells from I-As strains are required. Compatible with their phenotype as helper cells, some of the clones will provide help to primed B cells stimulating antibody production in an in vitro assay. When injected into recipients pretreated with pertussis and irradiation, clones that showed proliferation to mouse BP induced the development of inflammatory lesions in the CNS, with mortality of 28% of the recipients. T cell lines were also established in (BALB/c x SJL/J)F1 mice. In contrast to the homozygous SJL/J lines, these lines were highly encephalitogenic, inducing a high incidence of clinical and histologic EAE when injected in vivo.
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PMID:Characterization of T cell lines and clones from SJL/J and (BALB/c x SJL/J)F1 mice specific for myelin basic protein. 257 39

After a single intraperitoneal injection of formalinized whole-cell pertussis vaccine 5374 into CBA mice a drastic depletion of cells in the thymus accompanied by the enhancement of suppressor T-cells production is observed. T-cells inhibit the endogenous and exogenous colony-formation in the spleen by hematopoietic stem cells (CFUs). Treatment of thymus cells with the anti-I-Jk alloantiserum against a specific marker of suppressor T-cells in the presence of complement removes the inhibitory effect on CFUs proliferation and has a stimulatory action on the capacity of the marrow CFUs to form macroscopic hematopoietic colonies in the spleen compared with control ones. These results suggest probable involvement of I-J-bearing suppressor T-cells in the hematopoietic disorders induced by pertussis vaccine.
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PMID:[Stimulation of the suppressor activity in relation to hematopoietic cells in the mouse thymus as affected by pertussis vaccine]. 293 86

A single injection of killed whole-cell pertussis vaccine (strain 5374) into CBA mice (H-2k) was shown to induce a drastic depletion of cells in the thymus accompanied by the enhancement of suppressor T-cell activity. Thymus cells obtained from pertussis vaccine-treated mice were shown to inhibit the endogenous and exogenous colony formation in the spleen by haematopoietic stem cells (CFUs). Treatment of thymus cells with the anti-I-Jk alloantiserum against a specific marker of suppressor T-cells plus complement abolished the inhibitory effect on CFUs proliferation and had a stimulatory action on the capacity of the marrow CFUs to form macroscopic haematopoietic colonies in the spleen as compared to controls. These results suggest probable involvement of I-J-bearing suppressor T-cells in haematopoietic disorders induced by pertussis vaccine.
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PMID:Enhancement of haematopoiesis-directed suppressor activity in mice following Bordetella pertussis vaccine. 296 26

The cellular immune responses of Balb/c mice and Wistar rats immunized in hind footpads with intact killed Bordetella pertussis were found to differ from those of similar animals immunized with other bacteria including Bordetella bronchiseptica, Salmonella typhimurium and Escherichia coli. All the bacteria stimulated increases in cell number, proliferation and interleukin 2 (IL-2) production in popliteal lymph nodes which peaked 3-5 days after injection and decreased to resting levels by day 7. However, B. pertussis also caused a second peak in all three parameters at 11 days after immunization. This peak was not seen following injection with any of the other bacteria. Bordetella pertussis also caused systemic effects, increased cellular proliferation in bone marrow and thymus, with similar biphasic kinetics. It possesses a potent toxin, distinguishing it from the closely related B. bronchiseptica. The use of purified materials confirmed that the presence of this pertussis toxin (PT) was responsible for the later peak in stimulation, whereas lipopolysaccharide (LPS) in combination with PT and also the filamentous haemagglutinin (FHA) could mimic the early peak of stimulation. Primary immunization with B. pertussis was also shown to generate lymph node cells which responded in vitro to secondary challenge with B. pertussis cells, FHA or PT. Both proliferation and IL-2 production were enhanced, except with FHA which only increased IL-2 production. Lymph node cells from mice immunized with E. coli showed no such responses.
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PMID:The primary and secondary cellular immune responses to whole cell Bordetella pertussis vaccine and its components. 349 69


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