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)

The experienced morphologist can be extremely helpful to the clinician by virtue of his or her ability to distinguish among the various subtypes of reactive lymphocytoses. An awareness on the part of the clinician as to the nuances of subclassification may lead to earlier diagnosis of a disease process. Broadly, proliferations of normal lymphocytes point to infectious lymphocytosis or Bordetella pertussis infection. Proliferations of atypical lymphocytes, especially when minimum diagnostic criteria are present or there are four or more Downey III forms per 100 WBCs, suggest infectious mononucleosis. Proliferations of immunoblasts reflect hypersensitivity reactions to drugs or autoimmune disease. Proliferations of proplasmacytes or plasma cells favor viral hepatitis, drug reactions (notably to sulfa drugs), or rubella. Quantitative data may help refine the morphologic implications. Cumulatively, qualitative and quantitative data should lead the clinician to a judicious selection of confirmatory serologic tests and hence to earlier diagnosis.
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PMID:The lymphoid leukocytoses. 735 24

The normal migration route of B cells into follicular areas of spleen and lymph nodes is altered in the case of autoreactive cells that have bound self-antigen. To begin characterizing the molecular requirements for B cell migration into follicles, cells were treated with pertussis toxin (PTX), an inhibitor of signaling by many G protein-coupled chemokine receptors. Lymphocyte accumulation in the spleen is not inhibited by PTX and, therefore, the distribution of transferred cells was examined in this tissue. In contrast to untreated cells that localized predominantly in follicular areas within white pulp cords, PTX-treated B cells failed to enter white pulp areas altogether and accumulated in the splenic red pulp. T cells were also excluded from white pulp cords and in the case of both cell types, the adenosine diphosphate-ribosylating subunit of the toxin was required to block white pulp entry. These findings implicate a G protein-coupled receptor in lymphocyte migration into splenic white pulp cords. Exclusion of PTX-treated cells from all organized areas of secondary lymphoid tissues raises the possibility that the association observed between PTX treatment and predisposition to autoimmune disease results from inhibition of tolerance mechanisms that normally operate within secondary lymphoid tissues.
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PMID:Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords. 762 15

We constructed a transgenic mouse model that mimics the human autoimmune disease multiple sclerosis in its spontaneous induction and pathology. Transgenic mice were constructed expressing genes encoding a rearranged T cell receptor specific for myelin basic protein (MBP). T cell tolerance was not induced in the periphery, and functional, autoreactive T cells were found in the spleen and lymph nodes of these mice. Transgenic mice developed experimental allergic encephalomyelitis (EAE) following immunization with MBP and adjuvant plus pertussis toxin as well as with administration of pertussis toxin alone. Spontaneous EAE can develop in transgenic mice housed in a non-sterile facility but not in those maintained in a sterile, specific pathogen-free facility. This model system affords a unique opportunity to dissect the genetic and environmental variables that may contribute to the development of spontaneous autoimmune disease.
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PMID:Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. 767 52

In a preliminary study, we observed the production of TSH binding-inhibiting (TBII) and thyroid-blocking (TBAb) antibodies accompanied by lymphocytic infiltration of the thyroid in a pool of male BALB/c mice immunized with the extracellular domain (ECD) of the human TSH receptor (TSHR) expressed as a maltose-binding protein (MBP) fusion in bacteria. In the present study we evaluated the humoral response to the same antigenic preparation in a new series of individual male and female BALB/c mice immunized ip on day 0 with 100 micrograms MBP-ECD and days 25, 39, and 53 with 50 micrograms MBP-ECD in an adjuvant composed of aluminum oxide, magnesium hydroxide, and Bordetella pertussis vaccine. Mice immunized with MBP served as control. Individual sera and immunoglobulins were tested for TBII, TBAb, and thyroid-stimulating antibodies (TSAb) on days 0, 32, 46, and 60, and total circulating T4 levels were measured by RIA. Animals were killed on day 120, their thyroids were examined histologically, the infiltrates were characterized using monoclonal antibodies specific for T-cells (total, activated, helper, and suppressor), B-cells, and macrophages. Sera and immunoglobulins G of the MBP-treated control group were all negative for TSAb, TBAb, and TBII activity. The receptor-immunized mice, despite having high titers of antibodies to the immunogen in an enzyme-linked immunosorbent assay, displayed a heterogeneous response in terms of biological activity, with 3 of 7 female and 4 of 8 male mice having TBAb/TBII activities that persisted and whose activity increased throughout the experiment. No significant TSAb antibody activity was observed. Total T4 levels were also heterogeneous even before immunization, but 9 of 15 MBP-ECD-treated mice had levels below the normal range after immunization, and 7 of these also had TBII/TBAb activities. At the end of the experiment, only 4 of the MBP-ECD-treated female mice survived, but all of them had a severe lymphocytic infiltration of their thyroid, composed mostly of activated T-cells, although B-cells and macrophages were also present. A similar infiltrate was seen in 4 of 8 male MBP-ECD-treated mice. No infiltrate was observed in male or female MBP-treated mice. The model described demonstrates the feasibility of using the TSHR as an immunogen to overcome tolerance and mimics some characteristics of human autoimmune disease of the thyroid.
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PMID:Recombinant thyrotropin receptor and the induction of autoimmune thyroid disease in BALB/c mice: a new animal model. 795 39

Bordetella pertussis and Mycobacterium tuberculosis, routinely used to promote the development of autoimmune disease, were recently reported to also be effective in inducing protection against an autoimmune disease. Thus, we previously demonstrated that SJL/J and (SJL/J x BALB/c)F1 mice that are genetically susceptible to experimental autoimmune encephalomyelitis (EAE) become highly refractory to the induction of the disease following their exposure to B. pertussis and M. tuberculosis. In the present study, the pertussis toxin (PT) from B. pertussis and the purified protein derivative (PPD) of M. tuberculosis, were found to be sufficient to fully protect against EAE and thus may be the major bacterial components responsible for conferring protection. The 65-kDa heat-shock protein played only a marginal role in the protection against EAE induced by these bacteria. Both PT and PPD were protective when given before, but not after, the encephalitogenic challenge, and minute amounts (5-50 ng) emulsified in oil were sufficient to confer long-lasting resistance to EAE. The effect of PT or PPD on EAE differed from that of mitogens or bacterial superantigens, suggesting that their protection ability was not attributable merely to mitogenic or superantigenic properties. The mechanism of protection is not yet clear. Preliminary studies revealed a complex mechanism of protection whereby PPD and PT may operate differently. Thus, only PPD-induced, but not PT-induced, protection was transferrable by CD4+ T lymphocytes bearing an alpha beta T cell antigen receptor. Neither PT nor PPD had a protective effect on EAE mediated by preformed pathogenic T lymphocytes and it is most likely that they exert their protection by affecting the development of such T lymphocytes. How bacteria such as B. pertussis and M. tuberculosis can either enhance the development of an autoimmune disease or protect against the disease is not yet clear. However, identifying PT and PPD as the bacterial components active in protection may allow a better understanding of the modulatory effects of bacteria and point to the potential use of such bacterial products in immunomodulation of autoimmune diseases.
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PMID:Protection against autoimmune disease by bacterial agents. II. PPD and pertussis toxin as proteins active in protecting mice against experimental autoimmune encephalomyelitis. 809 58

Pertussis toxin (PTX) has been shown to potentiate autoimmunity in experimental autoimmune disease. The exact mechanism of this effect has not been determined; however, the modification of G proteins by ADP-ribosylation has been suggested. Here it is demonstrated that this modification may contribute to autoimmunity by the abrogation of transforming growth factor-beta (TGF-beta) growth-inhibitory signals. Anti-TGF-beta demonstrated the same effect on lymphocytes as high concentrations of PTX in vitro.
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PMID:Lymphocyte proliferation induced by pertussis toxin utilizes a pathway parallel to transforming growth factor-beta-sensitive growth. 840 Aug 94

Pertussis toxin (PTX) is the primary component responsible for eliciting the majority of biological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, Il-5r, Ly-35, Ly-4, and Tnfr-2.
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PMID:Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. 847 18

The nature of the autoimmune T cell response to myelin oligodendrocyte glycoprotein (MOG), recently recognized as a potential target antigen in multiple sclerosis (MS), has not yet been characterized, in contrast to the T cell reactivity to other potential target antigens in MS such as myelin basic protein and proteolipid protein. Here, we show that the encephalitogenicity of the recombinant Ig-like domain of human MOG is associated, in H-2 b mice, with an immunodominant T cell reactivity against a single region of MOG spanning amino acids 35-55, accounting for the previously reported strong encephalitogenic activity of pMOG 35-55. A single injection of pMOG 35-55 with or without administration of pertussis toxin was sufficient to induce severe clinical experimental autoimmune encephalomyelitis (EAE) in H-2 b mice. Encephalitogenic pMOG 35-55-specific T cell lines derived from C3H.SW (V beta b) mice were diverse in their TCR V beta gene usage (V beta 1, V beta 6, V beta 8 and V beta 15), although V beta 8.2 was most predominantly expressed (48%). However, V beta 8 + T cells may only be part of the encephalitogenic MOG-specific T cell repertoire in H-2 b mice, as demonstrated by the susceptibility of C57L (V beta a) mice to disease induced by pMOG 35-55. Encephalitogenic T cell lines from V beta a mice were also diverse in their TCR V beta gene usage (V beta 1, V beta 2, V beta 6, V beta 14 and V beta 16). Such a heterogeneous TCT V beta gene expression by pMOG 35-55/I-A b-reactive T cells from both V beta a and V beta b H-2 b mice suggested multiple epitopes within pMOG 35-55. Analysis of the pattern of reactivity by pMOG 35-55-reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40-48). However, optimal stimulation was obtained with longer peptides, with each additional amino acid flanking either the N or the C terminus differentially increasing the stimulatory capacity of pMOG 40-48. Nonetheless, pMOG 40-48 was the minimal encephalitogenic epitope for both V beta a and V beta b mice. Thus, the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse V beta gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope-directed, rather than TCR-targeted, approaches to immunospecific therapy for MOG-related autoimmune disease.
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PMID:Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse V beta gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor V beta b and T cell receptor V beta a H-2b mice. 889 62

The combination of genetic and environmental factors that contribute to human autoimmune responses has made potential triggers of these diseases difficult to identify. We examined how experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, is triggered using TCR-transgenic mice specific for myelin basic protein (MBP). In these TCR-transgenic mice, EAE can be actively induced and also occurs spontaneously. The incidence of spontaneous EAE in this model is largely confined to adolescence and early adulthood and is more prevalent among males than females, indicating that hormonal influences may contribute to triggering central nervous system autoimmune disease. Disease induction studies show that not all stimuli that activate MBP-specific T cells in vivo also induce EAE. Immunization with MBP peptide stimulates the transgenic T cells to produce Th1 cytokines; however, the activated T cells do not accumulate in the central nervous system and induce EAE unless pertussis toxin is also administered. EAE can be induced by intrathecal injection of either stimulated or nonstimulated transgenic T cells into nontransgenic or transgenic recipients. Therefore, gaining access to the central nervous system appears to be the critical step in this model for the induction of EAE, regardless of the activation state of the T cells.
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PMID:Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis. 920 Apr 91

Our studies addressed the questions of how self-reactive T cells escape tolerance and what stimuli cause these T cells to initiate autoimmune responses. We employed experimental allergic encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). Endogenous expression of myelin basic protein (MBP) induces tolerance in T cells that recognize one region of MBP, whereas T cells specific for a different region escape tolerance. Triggers of disease induction were investigated in a T-cell receptor (TCR) transgenic model in which the majority of T cells recognize the MBP epitope that does not induce tolerance. EAE occurs spontaneously in this model and the incidence of disease depends on microbial exposure. EAE can also be actively induced by immunization with MBP peptide accompanied by injection of pertussis toxin as well as by administration of pertussis toxin alone. Immunization with MBP peptide without pertussis toxin, however, stimulates the transgenic T cells, but the activated T cells do not accumulate in the central nervous system (CNS) or induce EAE. Our studies suggest that initiation of autoimmune disease involves complex interactions between the neuroendocrine system as well as the innate and specific immune systems.
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PMID:Initiation and regulation of CNS autoimmunity. 941 34


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