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Biomedical subjects

E B Mitchell

Publications and source records attributed to E B Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1984

Cutaneous basophil hypersensitivity to inhalant allergens in atopic dermatitis patients: elicitation of delayed responses containing basophils following local transfer of immune serum but not IgE antibody.

Inhalant allergens applied to the skin of sensitive atopic dermatitis patients by means of a modified patch test technique, induce acute eczematous lesions. These lesions contain basophils, eosinophils, mononuclear cells, and neutrophils and represent an example of human cutaneous basophil hypersensitivity. The role of IgE antibody in this eczematous reaction was studied by systemic and local passive transfer experiments. Plasma with high IgE antibody when infused into patients with hypogammaglobulinemia as part of their replacement treatment resulted, post infusion, in cutaneous mast cell and blood basophil sensitization as measured by quantitative skin testing and leukocyte histamine release. Subsequent patch tests on these patients using the house dust mite antigen, antigen P1, produced macroscopic erythematous responses containing mononuclear cells, and eosinophils but not basophils. Local transfer of atopic dermatitis serum with high IgE antibody produced weak macroscopic responses and in these lesions mononuclear cells and both basophils and eosinophils were present. The serum activity which allowed transfer of basophil and eosinophil recruitment was heat labile. Specifically purified antibody to the mite antigen P1 (containing IgE and IgG antibody), when transferred, allowed eosinophil but not basophil recruitment to patch test sites. These results suggest that while the allergen-induced patch test response may involve IgE antibodies, as well as the cells normally involved in delayed responses, another serum activity is also involved.

Adolescent↗
PubMed1984

T cell responses to the major allergen from the house dust mite Dermatophagoides pteronyssinus, Antigen P1: comparison of patients with asthma, atopic dermatitis, and perennial rhinitis.

Peripheral blood mononuclear cells (PBMC) from the majority of the allergic patients that we tested who were skin test-sensitive to the house dust mite Dermatophagoides pteronyssinus (D. pt.) (46/67) showed significant proliferation in response to the purified major allergen Antigen P1; PBMC from 14/15 nonsensitive controls showed no significant response. Optimal responses were seen with 10 micrograms Antigen P1/ml, but 21 of 43 patients tested showed significant proliferation at 0.01 microgram Antigen P1/ml. The results of three types of experiments showed that the responding cells were T cells, predominantly of the helper phenotype. First, purified T cells in the presence of irradiated or mitomycin C-treated antigen-presenting cells showed good proliferation to Antigen P1. Secondly, flow cytometry analysis showed a progressive increase in the percentage of viable cells bearing the Leu-3a marker--up to 88% by day 7--and demonstrated that the larger, blast-transformed cells bore this marker. Finally, interleukin 2 production was demonstrated in antigen-stimulated cultures at days 3 to 5, i.e., about 2 days before the peak of proliferation. When patients were grouped according to their disease symptoms, no clear differences were seen between the T cell responses of patients with asthma, eczema, or rhinitis, or with asthma and eczema, although patients with rhinitis alone tended to show weaker responses. Overall, there was a significant correlation between serum IgE antibody to Antigen P1 and T cell proliferation (rs = 0.579, p less than 0.001); however, excluding individuals with no IgE antibody, the quantitative correlation was poor (rs = 0.26, p less than 0.1). These results indicate that most patients showing immediate hypersensitivity to D. pt. have circulating T cells sensitized to Antigen P1. These sensitized T cells probably act as helper cells for antibody production, but may also play a role in the pathogenesis of allergic lesions and in the delayed or chronic symptoms of these allergic diseases.

Allergens↗
PubMed1983

Basophils in human disease.

Hypersensitivity reactions containing significant infiltrates of basophils occur in a large proportion of allergic diseases such as contact dermatitis, atopic dermatitis, and allergic rhinitis, and are quite deleterious. However, the potential usefulness of such responses can be recognized in similar reactions in guinea pigs responding to tissue invasion by complex multicellular parasites in which interactions occur between thymic-derived T lymphocytes, antibodies, and basophils in immune resistance responses. Perhaps inappropriate and deleterious allergic responses to pollens, chemicals, and insects is the price that we must pay for the ability to reject complex parasites.

Animals↗
PubMed1983

Quantitative assessments of IgG and IgE antibodies to inhalant allergens in patients with atopic dermatitis.

Using antigen-binding radioimmunoassays, we have measured class specific antibodies against two major inhalant allergens, antigen P1 from D. pteronyssinus and Rye I from grass pollen, in sera from 69 patients with atopic dermatitis. The results show that many of the patients have IgE ab to these allergens in keeping with their skin tests. In all cases, the IgE ab was paralleled by IgG ab to the same allergen. In many sera, IgE ab to these inhalant allergens made a significant contribution to the total serum IgE. With two other allergens to which these patients had not been exposed, specific IgE ab was detected in only one serum, whereas the 42 sera tested did not contain IgE ab to diphtheria toxin. Eleven of the adult patients with atopic dermatitis had no history of asthma and had strongly positive skin tests. This group of patients had levels of total IgE and specific ab to antigen P1 that were very similar to those found in a comparable group of patients who had both atopic dermatitis and asthma. Our recent finding that allergens applied to the skin can induce delayed eczematous lesions provides a mechanism by which allergens could contribute to skin lesions. Our present results support the view that specific sensitivity to common allergens should be taken into account in considering the causes of these patients' skin lesions.

Adolescent↗
PubMed1983

Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia associated with thymoma.

A 55-year-old male with a history of recurrent bacterial and viral infection was found to have hypogammaglobulinaemia in association with a benign thymoma. The patient lacked eosinophils and was deficient in basophils in both the peripheral blood and bone marrow. The absence of eosinophils in a skin challenge known to recruit these cells, and below normal total peripheral blood leucocyte histamine content further suggests a deficiency of eosinophils and basophils respectively. Abnormal suppressor T cell function was documented both phenotypically, using OKT monoclonal antisera, and functionally in pokeweed mitogen stimulated cultures. This patient is the first reported with a deficiency of both eosinophils and basophils occurring in the presence of hypogammaglobulinaemia and thymoma; these abnormalities may be related to the abnormal suppressor T cell function that is present.

Agammaglobulinemia↗
PubMed1983

Sensitization of circulating basophils in guinea pig recipients of passive transfer of cutaneous basophil hypersensitivity (CBH) with immune serum: antigen-specific histamine release in vitro.

An in vitro histamine release assay was used to test the hypothesis that passive sensitization of circulating basophils is associated with the activity of immune serum that transfer the ability to elicit cutaneous basophil hypersensitivity (CBH) reactions. Systemic i.v. transfer of several types of immune sera that mediate CBH also led to passive sensitization of circulating basophils for antigen-specific release of histamine in vitro. In addition, we found that immune serum passively sensitizes basophils in vitro. Thus immune sera had three activities that are probably interconnected: sera will 1) passively transfer CBH in vivo, 2) passively sensitize basophils in vivo, and 3) passively sensitize basophils in vitro. These results suggest that passive sensitization of circulating basophils by immune serum contributes to the mechanism by which antibodies transfer the ability to elicit CBH reactions.

Animals↗
PubMed1982

Reduction of bronchial hyperreactivity during prolonged allergen avoidance.

To study the long-term effects of avoiding domestic allergens, nine asthmatic patients who were allergic to dust mites lived in hospital rooms for two months or more. In all patients symptoms and early morning peak flows improved. In seven patients anti-asthma treatment could be reduced and it was possible to carry out repeated bronchial provocation with histamine. Five of these patients showed a progressive eightfold or greater increase in the concentration of histamine necessary to provoke a 30% fall in forced expiratory volume in one second (PD30). The increase in PD30 in the seven patients during their period of living in hospital was highly significant. Avoidance of important allergens seems not only to result in clinical remissions but in many cases also reduce bronchial hyperreactivity.

Adult↗
PubMed1982

Suppression of T cell-mediated cutaneous basophil hypersensitivity by serum from guinea pigs immunized with mycobacterial adjuvant.

Guinea pigs immunized with protein antigens emulsified with complete Freund's adjuvant (CFA) and skin tested at 3-4 wk have classical tuberculin-type delayed hypersensitivity (DH) reactions with few basophils present. However, recipients of T cells from these animals have delayed responses containing large basophil infiltrates and thus resemble basophil-rich cutaneous basophil hypersensitivity (CBH) responses that are elicited in animals immunized without CFA. This suggests that animals immunized with CFA have T cells with basophil-recruiting capacity but that this activity is suppressed. Using a transfer system, we found that immune serum from donors immunized with CFA had the ability to suppress the basophil-recruiting capacity of immune T cells. When immune serum and peritoneal exudate cells from guinea pigs immunized with CFA were co-transferred intravenously to normal recipients, the cell-mediated transfer of basophil-rich responses was suppressed. The responsible serum factor was antigen nonspecific, had an approximately 70,000 mol wt, and acted preferentially on cells from donors that express basophil-poor DH responses. Thus, tuberculin-type delayed hypersensitivity and CBH might be mediated by a common T cell, but the resulting basophil component of the delayed response depends on the modulation of T cell recruitment of basophils by factors in CFA-immune serum.

Animals↗
PubMed1982

Basophils in allergen-induced patch test sites in atopic dermatitis.

Atopic dermatitis often occurs in patients who have high IgE levels and positive immediate skin tests to several common allergens. However, there is considerable doubt about the role played by allergens in this disease. Patch testing for 48 h at superficially abraded skin sites revealed that allergens could induce eczematous lesions in atopic dermatitis patients but only in those who also gave a positive immediate skin reaction to the same allergen. Lesions induced by the purified house dust mite antigen, antigen P1 contained mononuclear cells, basophils, eosinophils, and neutrophils. These patients also had raised specific serum IgE against antigen P1, and their leucocytes released histamine upon exposure to the same antigen. Thus an acute eczematous lesion can be induced by the application of inhalant allergens to the skin.

Adolescent↗
PubMed1982

IgG1 antibody-dependent mediator release after passive systemic sensitization of basophils arriving at cutaneous basophil hypersensitivity reactions.

When antigen is injected into a 24-hr cutaneous basophil hypersensitivity (CBH) reaction of an actively sensitized guinea pig, local basophils degranulate and release histamine. This reaction is called cutaneous basophil anaphylaxis and may be antibody mediated. We now report passive sensitization of basophils at CBH sites by systemic transfer of anti-picryl immune serum. Keyhole limpet hemocyanin- (KLH) immunized animals were skin tested with KLH to elicit 24-hr CBH reactions at day 7. Anti-picryl serum was injected i.v. at various times. On day 7, blue dye was injected i.v., and then 24-hr CBH sites vs nearby normal skin were challenged with 0.1 microgram picryl-human serum albumin (Pic-HSA). An immediate increase in vascular permeability (blueing) was noted at normal skin sites due to systemic passive cutaneous anaphylaxis (PCA), and augmented blueing occurred at CBH sites compared with normal skin. Systemic passive sensitization of CBH sites occurred when antiserum was administered as little as 1 hr before challenge of CBH site. However, local administration of anti-picryl serum (as in a local PCA reaction) was not able to sensitize tissue basophils, whether antigen was administered locally or systemically. The serum factor that mediated cutaneous basophil anaphylaxis was heat-stable (56 degrees C X 4 hr) 7S IgG1 antibody. Electron microscopy of Pic-HSA-challenged CBH sites in animals that received IgG1 antibody showed that local basophils undergo anaphylactic degranulation by exocytosis. These studies suggest that basophils arriving at CBH reactions are sensitized for anaphylactic function by antibody that can be acquired in the circulation, but possibly not at the local site.

Animals↗
PubMedDate not supplied

A hapten-specific chimaeric IgE antibody with human physiological effector function.

Immunoglobulin E (IgE) has a central role in allergic reactions although it rarely exceeds 5 micrograms ml-1 even in the serum of severely allergic individuals. Both mast cells and basophils possess receptors which bind the Fc portion of IgE with high affinity; crosslinking of membrane-bound IgE by allergen results in degranulation of the cell and release of a variety of pharmacologically active mediator including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells has allowed us to construct a mouse cell line that secretes a chimaeric IgE, lambda 1 antibody whose heavy chain is composed of a human C epsilon constant region fused to a mouse variable (VH) region. This chimaeric IgE is specific for the hapten 4-hydroxy-3-nitro-phenacetyl (NP) and can, when crosslinked by antigen, trigger the degranulation of human basophils. When not crosslinked, however, the chimaeric IgE can prevent the passive sensitization of these cells by sera from allergic subjects.

Animals↗