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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an investigation of cell-mediated immunity against Bordetella pertussis, we found that B. pertussis infection in infants and in mice was associated with the induction of antigen-specific T cells that secrete IFN-g and IL-2, but not IL-4 or IL-5. This cytokine profile is characteristic of Th1 cells that mediate cellular immune responses against a range of intracellular pathogens. An examination of cytokine production following immunization with a three-component acellular vaccine, comprising inactive PT, FHA and pertactin adsorbed to alum, demonstrated that spleen cells from vaccinated mice produced high levels of IL-5, but no detectable IFN-g and low levels of IL-2. In contrast, peripheral blood mononuclear cells from vaccinated infants produced IL-2, IL-5 and IFN-g. These findings highlight significant differences in the immune responses generated by vaccination and natural infection with B. pertussis and demonstrate that the T-cell response induced with an acellular vaccine, although dominated by type 2 cytokines in mice, is more heterogeneous in infants with a Th0 or mixed Th1/Th2 cytokine profile.
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PMID:Bordetella pertussis-specific Th1/Th2 cells generated following respiratory infection or immunization with an acellular vaccine: comparison of the T cell cytokine profiles in infants and mice. 927 63

We have used a murine respiratory challenge model to examine the local T cell responses in the lung during infection with Bordetella pertussis. T cells from lung parenchyma and airways of naive and infected mice were refractory to both antigen and mitogen stimulation in the presence of lung macrophages. Furthermore irradiated mononuclear cells from the lungs suppressed antigen and mitogen-induced proliferation, but not IFN-gamma production, by splenic T cells. Removal of macrophages and stimulation of purified lung T cells in the presence of irradiated splenic antigen-presenting cells fully restored the response to mitogen. However, T cells purified from the lung during the acute phase of infection with B. pertussis failed to proliferate or produce detectable levels of IL-2, IL-4, IL-5 or IFN-gamma in response to purified bacterial antigens. In contrast, splenic T cells from these animals produced high levels of IL-2 and IFN-gamma and proliferated strongly to a range of bacterial components. Phenotypic analysis of bronchoalveolar lavage cells during the course of infection revealed transient infiltration of neutrophils, followed by macrophages, CD4+ T cells and smaller numbers of CD8+ T cells and gammadelta+ T cells. Cell surface expression of B7 on infiltrating macrophages and CTLA-4 on T cells did not change significantly during infection. However, expression of the CD28 co-stimulatory molecule was profoundly reduced on lung T cells during the acute phase of infection. In contrast, lung T cells from mice primed by B. pertussis infection or vaccination were resistant to CD28 down-regulation. These results suggest compartmentalization of T cell responses between the lung and the periphery during B. pertussis infection and that B. pertussis may have immunomodulatory properties on local T cell populations in the lungs of naive mice.
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PMID:Compartmentalization of T cell responses following respiratory infection with Bordetella pertussis: hyporesponsiveness of lung T cells is associated with modulated expression of the co-stimulatory molecule CD28. 948 95

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.
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PMID:Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children. 953 12

Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis which exerts a range of effects on the immune system, including the enhancement of IgE, IgA and IgG production, delayed-type hypersensitivity reactions, and the induction of experimental autoimmune diseases. However, the mechanism by which PT mediates adjuvanticity remains to be defined. In this investigation we have shown that PT can potentiate antigen-specific T cell proliferation and the secretion of IFN-gamma, IL-2, IL-4 and IL-5 when injected with foreign antigens. A chemically detoxified PT and a genetic mutant with substitutions/deletions in the S-1 and B oligomer components that abrogate enzymatic and binding activity displayed no adjuvant properties. In contrast, a non-toxic S-1 mutant devoid of enzymatic activity but still capable of receptor binding retained its adjuvanticity, augmenting the activation of both Th1 and Th2 subpopulations of T cells. In an attempt to address the mechanism of T cell activation, we found that PT stimulated the production of IFN-gamma and IL-2 by naive T cells and IL-1 by macrophages. Therefore potentiation of distinct T cell subpopulations may have resulted in part from the positive influence of IFN-gamma on the development of Th1 cells and the co-stimulatory role of IL-1 for Th2 cells. Furthermore, PT augmented expression of the co-stimulatory molecules B7-1 and B7-2 on macrophages and B cells, and CD28 on T cells, suggesting that the adjuvant effect may also be associated with facilitation of the second signal required for maximal T cell activation. This study demonstrates that the immunopotentiating properties of PT are largely independent of ADP-ribosyltransferase activity, but are dependent on receptor binding activity and appear to involve enhanced activation of T cells.
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PMID:Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28. 964 13

Pertussis infection is increasingly recognized in older children and adults, indicating the need of booster immunizations in these age groups. We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection. The expression of mRNA of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 in the peripheral blood mononuclear cells (PBMCs) was assayed by reverse transcription-PCR. The PBMCs of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) significantly proliferated in vitro after stimulation with the vaccine antigens. The PBMCs of seven infected individuals markedly proliferated in the presence of PT and FHA, but the cells of only two of these subjects responded to PRN. At least one of the antigens induced mRNA for IL-4 and/or IL-5 in the cells of 93% of tested vaccinees and patients, and FHA induced IFN-gamma mRNA in the cells of two-thirds of them. Expression of mRNA for IFN-gamma correlated with the production of the cytokine protein. Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization. These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren. Further, booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 (Th1) and Th2 type cytokines in similar manners. This observation supports the use of acellular pertussis vaccines for booster immunizations of older children, adolescents, and adults.
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PMID:Cytokine mRNA expression and proliferative responses induced by pertussis toxin, filamentous hemagglutinin, and pertactin of Bordetella pertussis in the peripheral blood mononuclear cells of infected and immunized schoolchildren and adults. 967 64

Cell-mediated immunity (CMI) to Bordetella pertussis and acellular pertussis vaccine constituents (pertussis toxin, pertactin, and filamentous hemagglutinin) were studied in peripheral blood mononuclear cells (PBMC) and T cell cultures from healthy adults with no record of vaccination against, or history of, pertussis. Similarly to stimulation with common recall antigens, PBMC proliferation was induced in 80%-100% of the cultures, depending on the specific B. pertussis stimulant. Proliferation did not occur when antigen-presenting cells were ablated by chemical or physical methods or with naive cord blood lymphocytes. B. pertussis antigen stimulation resulted in a preferential induction of type 1 cytokine profile, as shown by interferon-gamma and interleukin-2 (but no interleukin-4 or interleukin-5) gene transcripts and actual cytokine production by T cells. The data suggest that most healthy adults are repeatedly exposed to B. pertussis, with natural acquisition of antigen-specific CMI and a putatively protective type 1 cytokine pattern.
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PMID:Cell-mediated immune response of healthy adults to Bordetella pertussis vaccine antigens. 969 28

Eosinophil activation and subsequent release of inflammatory mediators are implicated in the pathophysiology of allergic diseases. Eosinophils are activated by various classes of secretagogues, such as cytokines (e.g., IL-5), lipid mediators (e.g., platelet-activating factor (PAF)), and Ig (e.g., immobilized IgG). However, do these agonists act directly on eosinophils or indirectly through the generation of intermediate active metabolites? We now report that endogenous PAF produced by activated eosinophils plays a critical role in eosinophil functions. Human eosinophils produced superoxide when stimulated with immobilized IgG, soluble IL-5, or PAF. Pretreating eosinophils with pertussis toxin abolished their responses to these stimuli, suggesting involvement of a metabolite(s) that acts on G proteins. Indeed, PAF was detected in supernatants from eosinophils stimulated with IgG or IL-5. Furthermore, structurally distinct PAF antagonists, including CV6209, hexanolamine PAF, and Y-24180 (israpafant), inhibited IgG- or IL-5-induced superoxide production and degranulation. Previous reports indicated that exogenous PAF stimulates eosinophil eicosanoid production through formation of lipid bodies. We found in this study that IgG or IL-5 also induces lipid body formation and subsequent leukotriene C4 production mediated by endogenous PAF. Finally, inhibition of cytosolic phospholipase A2, one of the key enzymes involved in PAF synthesis, attenuated both PAF production and effector functions of eosinophils. These findings suggest that endogenous PAF plays important roles in eosinophil functional responses to various exogenous stimuli, such as cytokines and Igs. Therefore, inhibition of PAF synthesis or action may be beneficial for the treatment of eosinophilic inflammation.
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PMID:Endogenous platelet-activating factor is critically involved in effector functions of eosinophils stimulated with IL-5 or IgG. 1007 49

The aim of the present study was to examine the in vivo effect of interleukin (IL)-12 on a murine model of asthma induced by Dermatophagoides pteronyssinus-derived Der p 1 allergen. C57BL/6 mice immunized with Der p 1 allergen adsorbed to alum/pertussis toxin developed a T-helper type 2 (Th2)-dominant immune response characterized by the presence of IgE antibody, airway eosinophil infiltration and increased production of Th2 cytokine. Intraperitoneal injection of IL-12 (1 or 0.1 microg per day) for 5 days (day -1 to +3) simultaneously with each immunization, inhibited the production of IgE and IgG1 antigen-specific antibodies, whereas production of IgG2a was strongly enhanced. In addition, mice receiving both doses of IL-12 showed a strong inhibition of IL-5 but up-regulation of IFN-gamma production by spleen cells stimulated with antigen. Administration of IL-12 also prevented antigen-induced eosinophil infiltration into the bronchoalveolar area in a dose-dependent manner and the primary inflammatory mediator serotonin in bronchoalveolar lavage (BAL) fluids was also reduced significantly. Taken together, the data indicate that IL-12 has a potent immunomodulatory effect on house-dust-mite-induced allergic disorders and may be used as an efficient agent for immunotherapy.
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PMID:Administration of interleukin-12 prevents mite Der p 1 allergen-IgE antibody production and airway eosinophil infiltration in an animal model of airway inflammation. 1010 39

We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (beta1), CD49d (alpha4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and the two IL-8 receptors IL8RA and IL8RB (C-X-CR1 and -CR2). In contrast, eosinophil adhesion was unaffected by PT, WEB 2086, or anti-IL8R mAbs. mAbs against CCR-3, IL-3, IL-5, and GM-CSF also had no effect. This study demonstrates that eosinophil and neutrophil adhesion to NPE in the FSA conforms to the multistep paradigm for leukocyte adhesion and can be used to model the molecular basis for adhesion to endothelium in the context of chronic inflammatory disease. Using this assay, we have observed significant differences in integrin usage between eosinophils and neutrophils and a striking difference in the mechanism of integrin activation. These differences could explain, in part, the preferential accumulation of eosinophils in diseases such as asthma.
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PMID:Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium. 1034 Sep 44

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting >/=7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination-induced systemic CMI may wane by 4 years of age but may be acquired or naturally boosted by symptomless or minor clinical infection by B. pertussis. This might explain, at least in part, the persistence of protection against typical pertussis in aP vaccine recipients despite a substantial waning of both Ab and CMI responses induced by the primary immunization.
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PMID:Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines. 1041 75


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