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

To understand the immunologic characteristics of pertussis toxin molecule and to explore the possibility of developing a synthetic vaccine, T cell epitopes on the enzymatic S1 subunit of pertussis toxin were studied by measuring the proliferative response of immune murine lymph node cells and T cell lines to Ag and to synthetic peptides. The maximum in vitro T cell proliferative response was obtained by stimulating immune lymphoid cells with 20 nM of the enzymatic S1 subunit. When the T cell proliferative response of murine lymphoid cells with different MHC backgrounds was tested, only mice bearing the H-2d haplotype were high responder to the S1 subunit. To determine T cell epitopes on the S1 subunit, the proliferative response of BALB/c immune lymphoid cells to several synthetic S1 peptides was measured. Only the peptide containing amino acid residues, 65-79, was recognized by BALB/c lymphoid cells and was confirmed to contain a T cell epitope by generating S1 specific BALB/c T cell line. By using this T cell line, the response of BALB/c mice to the S1 subunit as well as to peptide 65-79 was shown to be restricted to the I-Ad sublocus of class II Ag. Finally, we showed that lymph node cells of mice immunized with peptide 65-79 respond to the native S1 subunit.
 ...
PMID:Determination of T cell epitopes on the S1 subunit of pertussis toxin. 169 61

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.
 ...
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

Antibodies to surface Ig or to the B cell marker CD20 trigger resting human B cells in similar yet distinct ways. Either antibody induces five-fold increases in the expression of the protooncogene, c-myc, as detected with semi-quantitative Northern blot assays. The induction of c-myc mRNA by anti-IgM or anti-CD20 is blocked by inhibitors of protein kinase C (PKC) such as staurosporine and by pretreatment of B cells with phorbol esters to reduce cellular PKC levels. This suggests that PKC is involved in the pathways stimulated by both anti-IgM and anti-CD20. However, anti-CD20, unlike anti-IgM, does not activate significant increases in inositol triphosphate or intracellular-free calcium. Further, anti-CD20-triggered elevation of c-myc mRNA is inhibited by pertussis and cholera toxins, whereas the pathway initiated by anti-IgM if anything is stimulated by pertussis toxin and unchanged by cholera toxin. Further differences in the nature of these two signals were seen when the expression of adhesion/recognition molecules were examined. Anti-IgM consistently induces increased expression of the adhesion molecules CD54 (I-CAM-1) and B7/BB-1 on B cells, but anti-CD20 does not. Yet both anti-CD20 and anti-IgM increase class II MHC, CD18 (LFA-1 beta-chain) and LFA-3 levels. These data suggest that the way in which B cells are activated may influence their surface phenotype and possibly subsequent migration or cell-cell interactions.
 ...
PMID:Activation of dense human tonsilar B cells. Induction of c-myc gene expression via two distinct signal transduction pathways. 170 81

Experimental autoimmune uveitis (EAU) is an organ-specific autoimmune disease and has served as a model of certain ocular inflammatory conditions in man. The present study was aimed at separating the effects of MHC and non-MHC genes on the development of EAU in the rat. EAU-susceptible LEW (RT1l), EAU-resistant WKAH (RT1k), and WKAH.1L (RT1l) MHC congenic strain of WKAH background rats were immunized with retinal soluble antigen (S-Ag) in Freund's complete adjuvant (FCA). LEW rats showed typical EAU, while neither WKAH nor WKAH.1L congenic rats developed EAU. However, when an additional i.v. injection of Bordetella pertussis was given, all rat strains developed EAU. Furthermore, when immunized with peptide M, an 18-mer synthetic peptide, which corresponds to amino acid positions 303-320 of bovine S-Ag, and given an additional i.v. injection of B. pertussis, LEW and WKAH.1L rats developed EAU, whereas WKAH did not. When ACI (RT1avl), BUF (RT1b), LEJ (RT1j), W (RT1k), F344 (RT1lvl), BN (RT1n), NIG-III (RT1q), TO (RT1t), and SDJ (RT1u) rats were immunized with peptide M or S-Ag and then B. pertussis, all strains developed EAU by immunization with S-Ag plus B. pertussis, but only F344 and NIG-III developed EAU by immunization with peptide M. These findings suggest that susceptibility to EAU in rats is controlled by both MHC and non-MHC genes; and that in the absence of B. pertussis adjuvant, the form of disease induced by native S-Ag in FCA is governed by non-MHC gene(s). However, this effect of non-MHC gene(s) could no longer be observed when the rats were also injected with B. pertussis adjuvant at sensitization.
 ...
PMID:Regulation of experimental autoimmune uveitis in rats--separation of MHC and non-MHC gene effects. 174 50

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.
 ...
PMID:The mouse as a model of experimental autoimmune uveoretinitis (EAU). 238 8

The immunogenicity and reactogenicity of Bordetella pertussis vaccine are mediated in part by the S1 subunit of pertussis toxin (PT). To identify the immune epitopes in the S1 subunit of PT, synthetic peptides were prepared and tested for their capacity to induce antibodies in mice with different MHC genotypes. In BALB/c mice, peptides corresponding to sequences 1-17, 70-82 and 189-199 generate T cell proliferative responses, induce the production of antibodies capable of neutralization of the toxin in the Chinese hamster ovary-cell assay, and protect mice from a shock-like syndrome caused by alternate injections of BSA and PT. Protection and neutralization correlated with the ability of these peptides to elicit high anti-PT titers. Different B cell epitopes were detected in other inbred mouse strains. The antibody reactivity against synthetic peptides from two infants vaccinated with pertussis vaccine was tested. These infants had antibodies reactive to a variety of epitopes in the S1 subunit, including peptides 1-17, 70-82, 99-112, 135-145, and 189-199. Thus, it appears that there are multiple T and B cell epitopes in the S1 subunit of PT.
 ...
PMID:Multiple T and B cell epitopes in the S1 subunit ("A"-monomer) of the pertussis toxin molecule. 248 Mar 89

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.
 ...
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

We have investigated the responsiveness to thyroglobulin (Tg) plus complete Freund's adjuvant (CFA) and B. pertussis in a variety of inbred and MHC congenic strains of rats in terms of both Tg-autoantibody titres and histological thyroiditis index. Severity of thyroiditis was strongly Tg-dependent and closely related to the RT.1-MHC haplotype. Phenotypic examination of the inflammatory thyroid infiltrate using single and double indirect immunofluorescence techniques revealed a high proportion of macrophages and T lymphocytes, mainly of the cytotoxic/suppressor subset, in the high responder strains. Thyroid epithelial class II MHC expression although not prominent was strain-restricted and related to the amount of Ia+ leukocyte infiltrate.
 ...
PMID:Cellular infiltration in induced rat thyroiditis: phenotypic analysis and relationship to genetic restriction. 264 81

Animal models to control the serious neurological complications after vaccination against whooping cough are not available. In a recent paper pertussis vaccine induced acute encephalopathy in certain mouse strains (1). Healthy BALB/c mice died with shock-like symptoms after immunization with bovine serum albumin (BSA) and heat-killed pertussis. Mice not sensitized with BSA survived, and mice of strains with another H-2 type than H-2d were not susceptible. The authors concluded that the susceptibility to side effects to pertussis vaccine in mice and possibly in human is linked to the MHC. We tried to repeat the experiments reported by Steinman et al. in the hope that the murine encephalopathy model would be useful to evaluate possible neurological complications. In spite of having the same H-2d genotype, the BALB/c mice of two breeding stocks did not develop shock-like symptoms with fatal consequences after the last injection with BSA. This fact corresponds possibly with the author's observation that the pertussis vaccine encephalopathy is not under the control of H-2 genes alone. As shown in our tests the sudden deaths and encephalopathy in mice are not linked to BSA-sensitization because mice who received pertussis vaccine only showed the same symptoms as mice injected with BSA and vaccine. Histology did not indicate brain damage. It seems obvious that the deaths in our experiments were caused by the pertussis toxins present in the large numbers of bacteria given.
 ...
PMID:Is the acute encephalopathy test in mice suited for control of pertussis vaccines? 383 81

Our prior studies showed that gamma delta T cells were required to assist alpha beta T cells in the successful adoptive cell transfer of contact sensitivity (CS) responsiveness. These TCR-gamma delta+ regulatory T cells in immune spleen and lymph node were CD3+, CD4-, CD8+, nonantigen-specific, and non-MHC-restricted. In the current work, experiments were conducted to determine the mechanisms of how the gamma delta T cells were required to assist the alpha beta T cells in CS. We found that similar regulatory gamma delta T cells were in the spleen of normal mice, but not in the spleen of nude nor SCID mice, suggesting that the regulatory gamma delta T cells were present before immunization and required the thymus for differentiation, and also required rearrangements of gamma delta V gene segments. Treatment of cell transfer recipient mice with Bordetella pertussis (Bp), or with a low dose of cyclophosphamide (50 mg/kg), restored the ability of alpha beta+ gamma delta- T cells to transfer CS. This and other results suggested that Bp caused the CS-assisting gamma delta T cells to leave the lymphoid organs (such as the spleen) and enter the circulation, and only then to be able to assist the TCR-alpha beta+ CS-effector T cells. This effect needed the simultaneous i.v. injection of the CS-effector alpha beta T cells and the CS-assisting gamma delta T cells. The results also suggested that treatment with cyclophosphamide inactivated suppressor T cells in the recipients that acted to inhibit the alpha beta T cell transfer of CS, and thus that the CS-assisting gamma delta T cells acted by protecting the CS-effector alpha beta T cells from this endogenous suppression. This suppression of CS transfers also was eliminated by treatment of recipients with two different mAbs to determinants on suppressor T cells. In conclusion, we have described regulatory TCR-gamma delta+ CS-assisting/protecting T cells that are non-antigen-specific, non-MHC-restricted, CD3+, CD8+ gamma delta T cells that may assist adoptive transferring CS-effector alpha beta T cells by making these effector T cells resistant to suppressor T cells in the normal recipients.
 ...
PMID:Gamma delta T cells in normal spleen assist immunized alpha beta T cells in the adoptive cell transfer of contact sensitivity. Effect of Bordetella pertussis, cyclophosphamide, and antibodies to determinants on suppressor cells. 770 8


1 2 3 4 Next >>