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)

In Hooded Lister rats IgE responses may be induced by administration of antigen together with one of a number of adjuvants. The primary IgE response may subsequently be enhanced either specifically by a further exposure to antigen (booster response) or non-specifically by infection with helminth parasites (potentiated response). In the latter case the enhanced response is associated with a great increase in total serum IgE. The primary response itself is not significantly influenced by variations in the general theme of conventional immunization, including dose or route of administration of antigen, or the nature of the adjuvant employed. The booster response however is inhibited, a) in rats primed with a 'large' (e.g. greater than 100 microgram EA) dose of antigen and B. pertussis, and b) rats primed with any dose of antigen given in Al(OH)3 or CFA, and c) following repeated booster doses of soluble (i.e. unadjuvanted antigen even at a dosage of a few picogrammes. It is thought that each of the stimuli generate antigen specific suppressor T cells. Live worm parasites selectively, but non-specifically, stimulate heterologous antigen primed IgE responses. The evidence suggests that it may be this non-specific IgE stimulating effect rather than the parasite specific IgE response per se which leads to the great elevation of total serum IgE. Other immunoglobulin classes are not elevated in the same way. The potentiated IgE response is not susceptible to the suppressive influence generated by previous administration of large or repeated doses of the heterologous antigen. On the other hand, a parasite specific regulatory mechanism acts to prevent repotentiation of the heterologous (but not the parasite specific or total IgE) responses following reinfection. These results are discussed in relation to the work of others in rats and other species.
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PMID:Stimuli for the production and control of IgE in rats. 36 May 12

The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the V beta 8.5-J beta 2.3 gene combination, with extensive N region additions to both D beta 1 and D beta 2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different V beta 8 subfamily member (V beta 8.5) than the V beta 8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.
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PMID:T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats. 170 3

In a murine model of T cell-mediated autoimmune disease, experimental autoimmune encephalitis (EAE), 80% of all encephalitogenic T cell clones in H-2u mice use the V beta 8.2 TCR element. To induce EAE in susceptible strains of mice either heat-killed Bordetella pertussis organisms or Bordetella pertussis toxin (PT) must be injected in addition to Ag in CFA. We investigated the mechanisms by which PT facilitates the induction of EAE. Our data show, that PT interferes with the induction of Ag-induced peripheral T cell anergy. Furthermore it has a specific adjuvanticity for the autoantigen pAc1-11 in vivo and acts as a selective mitogen in vitro. We also tested the hypothesis that PT is a bacterial superantigen that specifically expands the V beta 8.2+ subset of T cells, thereby expanding the encephalitogenic T cell clones that are contained in this subset, so that the number of autoreactive T cells is brought over a critical threshold, necessary to induce autoimmune disease. Our data show that PT is not a superantigen. Staphylococcal enterotoxin B, a V beta 8.2-specific superantigen, does not enhance the immune response to the encephalitogenic peptide.
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PMID:Pertussis toxin prevents the induction of peripheral T cell anergy and enhances the T cell response to an encephalitogenic peptide of myelin basic protein. 171 74

A soluble fraction obtained from a testicular homogenate by precipitation with ammonium sulphate (ASPM) was emulsified with Freund's complete adjuvant (CFA) and injected into Wistar rats. At 50 days after the first immunization (total of three injections) the animals had developed moderate and multifocal testicular damage, characterized mainly by sloughing of the seminiferous epithelium. A delayed-type hypersensitivity response and circulating antibodies to ASPM were detected at different times with maximum levels at 50 days. The addition of Bordetella pertussis to the immunization did not increase the severity of the lesion but augmented the cellular and humoral immune response to ASPM. The phenotypic characterization of cells present in the lymph nodes draining from the site of immunization in animals injected with CFA alone (control group) revealed an increase in CD8+ T-cells and a low CD4/CD8 ratio. Conversely, rats immunized with CFA plus ASPM (experimental group) exhibited testicular damage and showed a significant decrease in CD8+ cells with a normal CD4/CD8 ratio. In conclusion, rats immunized with a testicular antigen developed focal aspermatogenic lesions and a concomitant specific immune response as well as lymph-node cell variations focused apparently on the CD8+ T-cell subpopulation.
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PMID:Testicular lesions and lymphocyte subpopulations in rats immunized with a soluble fraction of testicular homogenate. 176 27

A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.
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PMID:Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis. 200 94

An EAU model has been developed in the mouse using the retinal soluble antigen (SAg), and the interphotoreceptor retinoid-binding protein (IRBP). Immunogenetic studies indicate that sensitivity to disease is H-2 dependent, but some data suggest that non-MHC genes may also contribute to the regulation of EAU. IRBP was a more potent uveitogen than SAg. Ability to mount lymphocyte and antibody responses was exhibited both by EAU-susceptible and by EAU-resistant strains, and could not be used as a predictive parameter. Dependence of disease induction on variables of immunization was studied in B10.A mice (I-Ak) immunized with IRBP. Use of Bordetella pertussis as additional adjuvant was a prerequisite for successful disease induction. Use of purified pertussis toxin (PTX), rather than a suspension of pertussis bacteria, allowed reduction of the immunization protocol to a single dose of IRBP in CFA. Severity and incidence of disease, as well as its clinical course, were directly affected by the dose of antigen and PTX, and could be controlled by varying their respective doses. A spectrum of disease, from hyperacute to chronic, could be obtained. The chronic type of EAU tended to relapse, with lesions reappearing after a brief period of essential quiescence. The special advantages of the murine EAU model for the study of ocular autoimmunity are discussed.
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PMID:The mouse as a model of experimental autoimmune uveoretinitis (EAU). 238 8

Autoimmune glomerulonephritis was induced in chickens by immunization with human, bovine, turkey or chicken glomeruli in CFA. The influence of dose and of the pertussis vaccine was evaluated in two other separate experiments. The highest incidence of glomerulonephritis was observed in chickens immunized with human glomeruli, followed in descending order by bovine, chicken and turkey glomeruli. Capsular adhesions were seen in the last three groups. Epithelial crescents were seen only in the group immunized with chicken glomeruli. Interstitial lymphocytic infiltration was seen in 54% and 71% of chickens immunized with bovine and chicken glomeruli, respectively. The severity of the disease increased with time and the number of immunizations. IgG deposits on the GBM were seen in 92% (22/24), 54% (13/24), 50% (12/24) and 33% (8/24) of animals immunized with human, bovine, turkey and chicken glomeruli, respectively. Severity of disease was directly related to the amount of glomeruli injected. However, IgG deposits showed an inverse correlation with antigen dose. The disease was always less severe in chickens immunized with bovine glomeruli-CFA plus pertussis, as compared to bovine glomeruli-CFA immunized chickens. These studies demonstrate that the type of GBM antigen and immunization method play a significant role in the resultant histologic lesions in this model, and define conditions for optimal production of disease.
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PMID:Experimental autoimmune glomerulonephritis in chickens: I. Influence of source of antigen, dose and adjuvant. 297 15

Glycosylation-enhancing factor (GEF) and IgE-potentiating factor were detected in culture supernatants of rat mesenteric lymph nodes (MLN) cells obtained 14 days after infection with Nippostrongylus brasiliensis (Nb), but not in supernatants of MLN cells of 8-day Nb-infected rats. Both factors were also released from T cells upon antigenic stimulation of KLH + alum-primed spleen cells. The GEF from the Nb-infected rats and KLH + alum-primed spleen cells had affinity for p-aminobenzamidine agarose and were inactivated by phenylmethylsulfonylfluoride, an inhibitor of serine proteases. These results indicate that the GEF obtained in the two systems is a serine protease and is identical to that obtained by stimulation of normal T cells with lymphocytosis-promoting factor (LPF) from Bordetella pertussis. The concomitant formation of IgE-potentiating factor and GEF by Nb infection, by antigenic simulation of KLH + alum-primed spleen cells, and by treatment of rats with Bordetella pertussis vaccine suggests that the serine protease is involved in a common pathway leading to the selective formation of IgE-potentiating factor. In contrast, glycosylation-inhibiting factor (GIF) is always found during the selective formation of IgE-suppressive factor. IgE-suppressive factor and GIF were formed by MLN cells of 8-day Nb-infected rats and KLH-CFA-primed spleen cells. GIF was detected in culture supernatants of T cell hybridomas 23A4 and 23B6, which form unglycosylated IgE-binding factors upon incubation with IgE. GIF obtained from all of these sources bound to monoclonal anti-lipomodulin. These findings indicate that GIF or lipomodulin is involved in all systems, which leads to the selective formation of IgE-suppressive factor. However, the formation of GIF was not restricted to those conditions in which IgE-suppressive factor was selectively formed. The culture supernatants of MLN cells of 14-day Nb-infected rats and antigen-stimulated KLH + alum-primed spleen cells contained a small amount of GIF, which could be detected after inactivation of GEF. It appears that T cells from these sources formed GEF and GIF, but that GEF overcame the effect of GIF on glycosylation of IgE-binding factors. The results indicate that the nature and biologic activities of IgE-binding factors are decided by the balance between GEF and GIF formed by T cells.
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PMID:Modulation of the biologic activities of IgE-binding factor. V. The role of glycosylation-enhancing factor and glycosylation-inhibiting factor in determining the nature of IgE-binding factors. 636 37

Pertussigen, one of the biologically active proteins from Bordetella pertussis, was found highly active as an adjuvant to promote the induction of experimental allergic encephalomyelitis (EAE) in (SJL X BALB/c)F1 mice that had received at the same time an injection of mouse spinal cord (MSC) homogenized in complete Freund's adjuvant containing 4 mg of Mycobacterium tuberculosis H37RA per milliliter (CFA-H37). In this system 2 mg of MSC induced EAE, but a dose of 4 mg was more effective. As little as 250 ng of pertussigen facilitated induction of EAE, and 400 ng uniformly did so. Pertussigen was most effective when given iv from 1 day before to 5 days after administration of MSC homogenized in CFA-H37, when a uniform and severe disease was induced 11-13 days after immunization. Pertussigen given as late as 20 days after MSC-CFA-H37 still precipitated a mild form of EAE which appeared 8-12 days after the injection of pertussigen. When pertussigen was given 5 days after immunization, a chronic, nonfatal type of EAE was induced, and this persisted for the entire 74 days of observation. Histologic findings in the brain and spinal cord 15 days after sensitization in mice which received pertussigen and developed EAE showed perivascular infiltrates consisting mainly of mononuclear cells.
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PMID:Elicitation of experimental allergic encephalomyelitis (EAE) in mice with the aid of pertussigen. 660 26

Experimental myasthenia gravis (EMG) was elicited in female AO rats, 8-12 weeks of age, by injection of 100 micrograms/rat Torpedo marmorata acetylcholine receptor (AChR)-protein incorporated in CFA. Bordetella pertussis, 24 x 10(9) microorganisms, rat, was injected simultaneously as additional adjuvant. Rats were sacrificed on the day of appearance of the clinical signs of EMG, and thymuses were used for histological analysis using stereologic method, and thymocyte subsets were estimated by flow cytometry. Two and three colour fluorescence was applied to determine DN (CD4-CD8-), DP (CD4+CD8+), SP-CD4+ (CD4+CD8-) and SP-CD8+ (CD4-CD8+) subsets, as well as thymocytes expressing TCR alpha/beta. Rats immunized with BSA and rats injected with saline were used as controls. From 56 rats immunized with AChR-protein, 44 rats developed the disease, between day 7 and 11 after immunization. Severity of disease varied from + to + + +. Stereologic analysis of tissue sections revealed a highly significant reduction of thymic cortex and hypertrophy of medulla in EMG thymuses. Similar, but very slight changes were observed in thymuses of rats immunized with BSA. Percentages of DN, SP-CD4+, and SP-CD8+ subpopulations were significantly increased, while the percentage of DP population showed a marked decrease. These preliminary data suggest an alteration of thymocyte maturational events. Whether these changes could be responsible for the initiation of autoimmunity, or are occurring as a secondary phenomenon, after EMG was already established following the injection of cross reactive antigen, is a matter for discussion.
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PMID:Thymus changes in experimentally induced myasthenia gravis. 790 60


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