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)

Mice were immunized with whole killed blood stage Plasmodium yoelii parasites in 15 adjuvant formulations then boosted and challenged with parasitized blood. Five of six groups immunized with the Ag in oil-in-water emulsions or formulations without oil were protected. Formulations that induced protection contained saponin, pertussis, copolymer P1004, and detoxified RaLPS. In contrast, none of nine groups of animals immunized with Ag in water-in-oil emulsions were protected. Ineffective adjuvants included CFA and water-in-squalene emulsions with copolymer L141 plus detoxified RaLPS, dimethyldioctadecyl ammonium bromide, and mycobacterial cell wall skeletons. Antibody was measured by ELISA against disrupted parasites and by indirect fluorescent antibody (immunofluorescence) using intact parasites. Protection was associated with antibody of the IgG2a isotype detected by immunofluorescence but not with other isotypes detected by immunofluorescence or any type antibody detected by ELISA. The water-in-oil adjuvants induced high titers by ELISA but low titers by immunofluorescence. These results, together with Western blot analyses, suggested that adjuvant vehicles control the specificity of antibody and that this, in turn, is essential for induction of protective immune responses in this model.
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PMID:Role of adjuvants in the modulation of antibody isotype, specificity, and induction of protection by whole blood-stage Plasmodium yoelii vaccines. 825 12

Experimental autoimmune anterior uveitis (EAAU), a model of uveitis induced by sensitization to melanin associated antigen (MAA) derived from the iris and ciliary body, closely resembles human acute anterior uveitis. The immunopathogenesis of EAAU was studied by immunohistochemical detection of immune cells and the expression of Ia, ICAM-1 and LFA-1 antigens. Male Lewis rats were immunized with bovine MAA, mixed with CFA and pertussis toxin in the hind foot pad. Animals were examined daily by slit-lamp biomicroscopy and serially sacrificed up to 30 days. Immunohistology of the enucleated eyes was performed with monoclonal antibodies W3/25 (CD4), OX-8 (CD8), ED2 (macrophage), OX-33 (B cell), OX-6 (Ia), IA29 (ICAM-1) and WT.1 (LFA-1). During each stage of EAAU, CD4+ T cells predominated over both CD8+ T cells and macrophages in the uvea. Very few B cells were detected during each stage of EAAU. EAAU could not be induced by the adoptive transfer of sera obtained from immunized animals. Low levels of constitutive ICAM-1 and Ia were observed. An increase in ICAM-1 expression was first noted on the epithelial cells of the uveal tract and RPE on day 9 post immunization and preceded LFA-1 and Ia upregulation by approximately 2 days. The immunopathogenesis of EAAU appears to be linked to the presence of the CD4+ T cells.
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PMID:Immunohistochemical studies on melanin associated antigen (MAA) induced experimental autoimmune anterior uveitis (EAAU). 852 6

Experimental autoimmune dacryoadenitis was produced in Lewis rats by immunization with a single intradermal administration of a 3M KCl extract of exorbital lacrimal gland in CFA, when enhanced by simultaneous i.v. injection of killed Bordetella pertussis. No significant lacrimal lesions were observed in control animals immunized with the extracts of Harderian or salivary glands. Gel filtration of the 3M KCl extract on Sephacryl S-300 column yielded three protein fractions. Only fraction III (MW = 10-55K) induced marked dacryoadenitis following a single injection of 2.0 mg protein in CFA plus pertussis. The infiltrates in the exorbital lacrimal lesions were first apparent around the ducts and associated vasculature. From this area, the infiltrates appeared to spread to the acini drained by these ducts, ultimately involving as much as 30-50% of the gland. The affected glands most commonly showed a diffuse nongranulomatous infiltrate of small lymphocytes, macrophages, and plasma cells; this was focal in nature, involving acinar atrophy and breakdown, and replaced the normal architecture in extreme cases. The Harderian and salivary glands were uninvolved in these animals, suggesting a restricted specificity of this response. Lewis rats immunized with exorbital lacrimal gland fractions I or II in CFA plus pertussis showed only minimal lesions, similar to controls receiving CFA and pertussis without antigen. These findings suggest that an autoantigen exists in the lacrimal gland of the rat that is capable of inducing a specific lymphoproliferative dacryoadenitis.
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PMID:Experimental autoimmune dacryoadenitis. I. Lacrimal gland disease in the rat. 859 7

B7-1 and B7-2 are well characterized costimulatory ligands on Ag presentation cells for the CD28 and CTLA4 receptors on T cells. The fusion protein CTLA4Ig can block this interaction and prevent specific T cell activation. The development of fatal CD4+ T cell-mediated experimental allergic encephalomyelitis (EAE) in susceptible female Lewis rats was optimized by immunization with 20 mg of guinea pig spinal cord homogenate in CFA on day 0 with three doses of 1 microgram pertussis toxin given i.v. on days 0, 3, and 7. This immunization regimen uniformly resulted in the development of severe clinical neurologic signs of EAE with 100% mortality by day 17 postimmunization. Treatment with 0.5 mg/dose of rhCTLA4-Ig on days - 2, 0, 3, 6, 9, 12, 15 and 18 significantly decreased the incidence, delayed the onset, and reduced the severity of clinical EAE (p = 0.0002 vs control by the Mann-Whitney U test) enough to completely prevent fatal EAE, whereas treatment with control human IgG had no effect. Histologically, perivascular neutrophilic infiltrates were also dramatically decreased in the spinal cords of animals treated with CTLA4 but not in those treated with control human IgG. The proliferative response to encephalitogenic Ags (guinea pig myelin basic protein and proteolipid protein) by lymph node cells from animals immunized with guinea pig spinal cord 10 days before was also significantly suppressed in vitro by CTLA4Ig (1 microg/ml). However, the protective effect of CTLA4Ig could be completely prevented by the daily i.p. administration, from day 0 to 10, of exogenous human rIL-2 (180,000 IU). These results indicate a critical requirement of the costimulatory B7/CD28 pathway early in the development of CD4+ T cell-mediated EAE in the rat.
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PMID:Inhibition by CTLA4Ig of experimental allergic encephalomyelitis. 864 42

Administration of antigen suspended in incomplete Freund's adjuvant supplemented with either heat-killed Mycobacterium tuberculosis (complete Freund's adjuvant, CFA) or Bordetella pertussis toxin sensitizes animals so that subsequent antigen challenge leads to delayed-type (DTH) or immediate type hypersensitivity (ITH) responses, named type IV and type I, respectively. Appropriate timing of administration of drugs with respect to immunization or antigen challenge allowed to detect predominantly immunosuppressive, antiinflammatory or antianaphylactic activities. Among the reference drugs tested, only cyclosporin A (CsA) and dexamethasone (Dex) markedly inhibited DTH reaction, due to their immunosuppressive and antiinflammatory activities, respectively, whereas leflunomide and indomethacin resulted less potent. On the other hand, only dexchlorpheniramine, a histamine-receptor antagonist, afforded significant protection against anaphylactic shock, a form of ITH. Two new chemical entities were studied according to this protocol: ITF 1697, a chemically stabilized C-reactive protein-derived tetrapeptide, and ITF 2018, a leflunomide analogue. Data obtained with these new compounds showed that ITF 1697 has antianaphylactic activity, while ITF 2018 is endowed, mainly, with antiinflammatory activity. These results show that, through appropriate timing of administration, established in vivo models of immunologically mediated disease states allow an accurate profiling of the effects of pharmacologically active molecules and the detection of unsuspected activities for new drugs.
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PMID:Use of type I and type IV hypersensitivity responses to define the immunopharmacological profile of drugs. 917 84

The objective of this paper was to determine whether intrathymic injection of retinal S-antigen (S-Ag) can prevent experimental autoimmune uveoretinitis (EAU) in Lewis rats. Lewis rats were injected intrathymically with 25-100 micrograms of S-Ag in 100 microliters split between thymic lobes. Controls received vehicle alone (PBS) or 100 micrograms of BSA. Animals were immunized two weeks later with 100 micrograms of S-Ag in CFA with or without pertussis toxin (0.5 micrograms/rat). Clinical ocular disease was confirmed by histopathology. Splenocytes and lymph node cells were assayed, in vitro, for their ability to proliferate in response to various concentrations of S-Ag. Furthermore, attempts were made to adoptively transfer protection to naive rats using spleen cells from intrathymically injected animals and to adoptively transfer EAU to protected rats using Con A activated cells from affected animals. Intrathymic injection of S-Ag reduced the incidence of EAU in animals subsequently immunized with S-Ag and pertussis, and prevented it entirely in rats immunized in the absence of pertussis. Splenic and lymph node cells from intrathymically injected animals showed reduced reactivity to S-Ag compared to controls, suggesting that intrathymic S-Ag injection may have rendered them tolerant to this antigen. We were unable to adoptively transfer protection to naive rats, nor were intrathymically injected rats protected from EAU induced by the adoptive transfer of primed lymph node cells. These data demonstrate that intrathymic S-Ag injection can be an effective method for protection from EAU, apparently through the induction of immunological tolerance and not active suppression. The tolerance was not absolute and could be overcome by increasing the intensity of the antigenic challenge.
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PMID:Prevention of experimental autoimmune uveoretinitis by intrathymic S-antigen injection. 932 61

In order to replicate a recently described murine model of Graves' disease, we immunized AKR/N (H-2k) mice i.p., every 2 weeks, with either a clone of fibroblasts expressing both the human TSH receptor (hTSHR) and murine major histocompatibility complex (MHC) class II molecules or with fibroblasts expressing the MHC class II molecules alone. Mice were bled, and their thyroid hormone levels measured, at 6, 12, and up to 18 weeks after the first immunization. Between 11-12 weeks after immunization, a significant number of mice began to die spontaneously and were found to have developed large goiters. Thirty to 40% of mice immunized with hTSHR transfected fibroblasts showed markedly increased serum T3 and T4 hormone levels by 12 weeks compared with controls, with the highest thyroid hormone levels being T3: 420 ng/dl (normal < 70) and T4: 16.5 microg/dl (normal < 5). The murine serum demonstrated the presence of antibodies to the TSHR, as evidenced by inhibition of labeled TSH binding to the hTSHR, and these sera had in vitro thyroid stimulating activity. Many of the hyperthyroid mouse exhibited weight loss and hyperactivity and, on examination, their thyroids had the histological features of thyroid hyperactivity including thyroid enlargement, thyroid cell hypertrophy, and colloid droplet formation--all consistent with Graves' disease. In contrast, a small number of mice (< 5%) developed hypothyroidism with low serum T4 levels and markedly increased TSH concentrations and evidence of thyroid hypoplasia. Both hyperthyroidism and hypothyroidism were successfully transferred to naive mice using ip cells of immunized mice. Surprisingly, hypothyroidism occurred in many recipient mice even after transfer from hyperthyroid donors. These results confirmed that immunization with naturally expressed hTSHR in mammalian cells was able to induce functional TSHR autoantibodies that either stimulated or blocked the mouse thyroid gland and induced hyperthyroidism or thyroid failure. Furthermore, both blocking and stimulating antibodies coexisted in the same mice as evidenced so clearly by the transfer of hypothyroidism from hyperthyroid mice. The addition of a Th2 adjuvant (pertussis toxin) caused approximately 50% of the animals to become hyperthyroid beginning early at 9 weeks, whereas a Th1 adjuvant (CFA) delayed the disease onset such that only 10% were hyperthyroid by 12 weeks. As with human autoimmune thyroid disease, the T cell control of this murine model may be critical and requires more extensive investigation.
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PMID:Regulation and transfer of a murine model of thyrotropin receptor antibody mediated Graves' disease. 1006 67

Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14-36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.
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PMID:Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets: the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule. 1087 88

IL-12, a cytokine produced by microglia, may regulate cellular immunity at a localized level in the CNS. To investigate this further, we examined the consequences of peripheral immune stimulation without specific autoantigen in wild-type or transgenic (termed GF-IL12) mice with astrocyte production of the bioactive IL-12 p75 heterodimer. Active immunization with CFA and pertussis toxin, a procedure known to stimulate a robust type 1-biased immune response, produced CNS immune pathology from which GF-IL12 but not wild-type mice developed signs of clinical disease consisting of loss of activity, piloerection, mild tremor, and motor change. All immunized mice had some degree of mononuclear cell infiltration into the brain; however, the severity of this was markedly increased in GF-IL12 mice where leukocytes accumulated in perivascular and parenchymal locations. Accumulating cells consisted of CD4(+) and CD8(+) T cells and macrophage/microglia. Moreover, expression of cytokines (IFN-gamma and TNF), chemokines (IFN-inducible protein-10 and RANTES), the immune accessory molecules, MHC class II, B7.2, ICAM-1 and VCAM-1, and NO synthase-2 was induced in the CNS of the GF-IL12 mice. Therefore, peripheral immunization of GF-IL12 but not wild-type mice can provoke active type 1 immunity in the brain-a process that does not require CNS-specific immunizing autoantigen. These findings indicate that the cytokine milieu of a tissue can dramatically influence the development of intrinsic immune responses and associated pathology.
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PMID:Induction of type 1 immune pathology in the brain following immunization without central nervous system autoantigen in transgenic mice with astrocyte-targeted expression of IL-12. 1167 69

The CXC chemokine ligand (CXCL)10 is induced locally in the CNS in diverse pathologic states. The impact of CXCL10 production in the CNS was examined in transgenic mice with astrocyte-directed production of this chemokine. These glial fibrillary acidic protein (GF)-CXCL10 transgenic mice spontaneously developed transgene dose- and age-related leukocyte infiltrates in perivascular, meningeal, and ventricular regions of the brain that were composed of, surprisingly, mainly neutrophils and, to a lesser extent, T cells. No other overt pathologic or physical changes were evident. In addition, the cerebral expression of a number of inflammation-related genes (e.g., cytokines) was not significantly altered in the transgenic mice. The extent of leukocyte recruitment to the brain could be enhanced markedly by peripheral immunization of GF-CXCL10 mice with CFA and pertussis toxin. This was paralleled by a modest, transient increase in the expression of some cytokine and chemokine genes. Analysis of the expression of the CXCL10 receptor, CXCR3, by the brain-infiltrating leukocytes from immunized GF-CXCL10 transgenic mice revealed a significant enrichment for CXCR3-positive cells in the CNS compared with spleen. The majority of cells positive for CXCR3 coexpressed CD3, whereas Gr1-positive granulocytes were negative for CXCR3 expression. Thus, while astrocyte production of CXCL10 can promote spontaneous and potentiate immune-induced recruitment of leukocytes to the CNS, this is not associated with activation of a degenerative immune pathology. Finally, the accumulation of neutrophils in the brain of GF-CXCL10 transgenic mice is apparently independent of CXCR3 and involves an unknown mechanism.
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PMID:Leukocyte infiltration, but not neurodegeneration, in the CNS of transgenic mice with astrocyte production of the CXC chemokine ligand 10. 1213 78


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