Experimental delayed type allergy without demonstrable antibodies: II. In vitro activity of reticulo-endothelial cells

In guinea-pigs a delayed type allergy against sheep erythrocytes (SE) was obtained without the presence of cytophilic antibodies. The affinity for the antigen of the reticulo-endothelial cells of such animals was studied in vitro and compared with the affinity of cells of animals with delayed type allergy and with cytophilic antibodies.Spleen cells and peritoneal leucocytes from animals with allergy and with antibodies had an increased affinity for SE as shown by increased adherence or increaed phagocytosis. This proved to be due to cytophilic antibodies. Lymph node cells also showed an increased adherence which was only partly due to cytophilic antibodies, as one group of cells showing adherence only appeared after active immunization (antibody forming cells?).The cells of animals with delayed type allergy without antibodies never showed adherence or increased phagocytosis.Thus when the presence of cytophilic antibodies was definitely excluded no evidence could be obtained that reticulo-endothelial cells of animals with delayed type allergy reacted in vitro with the antigen.     

Studies on cutaneous allergy: Cytophilic antibodies, passive cutaneous anaphylaxis and delayed type allergy

In guinea-pigs a delayed type allergy against sheep erythrocytes (SE) or ovalbumin without detectable circulating and macrophage-cytophilic antibodies was produced by immunization with antigen—antibody complexes. In these animals skin reactions to SE were not enhanced by admixture of macrophages, neither when the macrophages had been sensitized with cytophilic antibodies in vitro, nor when the SE had been (partially) ingested within the macrophages after incubation with opsonizing antibody in vitro.

Also in these animals no enhanced delayed skin reactions to SE were obtained if before the injection of the antigen the skin had been infiltrated with cytophilic antibody or passive cutaneous anaphylaxis (PCA) antibody.

Thus, no enhancing effect of cytophilic antibody on delayed cutaneous hypersensitivity reactions could be obtained.

Furthermore, in guinea-pigs with delayed type allergy to ovalbumin, no enhancing effect of delayed allergy on passive cutaneous anaphylaxis was observed.

     

Atopic allergy and delayed type hypersensitivity in Estonian children

BACKGROUND: A shift in the balance ofT helper (Th) cell subsets towards a polarized Th2 population is generally accepted to occur in atopic disease, however, both Th1 and Th2 disorders have increased over the past decades in Western communities. OBJECTIVE: The aim of our study was to investigate delayed type hypersensitivity (DTH) response in atopic and non-atopic children in a population with a low prevalence of allergic disorders. METHODS: Skin prick tests (SPT) were performed with fresh egg white and extracts of five inhalant allergens, i.e. cat, dog, house dust mite (Dermatophagoides pteronyssinus), birch and timothy, and DTH response was evaluated by Multitest CMI in 72 Estonian 4- to 6-year-old children. RESULTS: The frequency of response to diphtheria was significantly increased in SPT-positive children (55% vs. 26%, chi2 = 5.5; P = 0.038). The induration to diphtheria (2.4 +/- 0.5 vs. 0.9 +/- 0.2 mm; P = 0.004), and tetanus (3.5 +/- 0.6 vs. 2.1 +/- 0.3 mm; P = 0.025) was significantly greater in the SPT-positive children. The cumulative size of induration in the positive DTH tests was significantly greater in the SPT-positive children (9.0 +/- 1.2 vs. 5.2 +/- 0.6 mm, P = 0.01). CONCLUSION: In this group of children our findings do not support the hypothesis of an immune deviation with decreased Th1 and increased Th2 responses leading to atopic disease, but rather a process of immune modulation whereby both Th1 and Th2 responses are increased in atopic subjects.     

Mercurochrome allergy. Immediate and delayed hypersensitivity

We describe eight patients suffering from Mercurochrome allergy. Patch and prick tests were carried out with the following organic and inorganic mercury compounds: thimerosal, Mercurochrome, phenylmercuric acetate, phenylmercuric nitrate, metallic mercury, and mercuric chloride, and with sodium fluorescein. Two patients had an anaphylactic reaction a few minutes after application of Mercurochrome. The prick tests with Mercurochrome were positive and they were negative with the other tested products. All patch tests were negative. In the other six patients, the clinical picture was local eczema, and the patch tests were all positive with Mercurochrome and the inorganic mercuric derivatives. Positive patch tests with thimerosal were found only in two patients, and only one had a positive patch test with salts of phenylmercury. In four patients, the prick test with Mercurochrome, negative in immediate reading, gave a late eczematous reaction.     

The induction of delayed hypersensitivity by macrophage-associated antigen: The role of macrophage cytophilic antibody

The regulation of the immune responses by antibody administered passively on peritoneal exudate cells (PEC) was studied in guinea-pigs. The immunogenicity of sheep red blood cells (SRBC) associated with PEC for the induction of delayed hypersensitivity (DH) to soluble erythrocyte antigen was enhanced when PEC were incubated with anti-SRBC antibody. In contrast, the antibody response to SRBC was depressed. This phenomenon was only observed with specific antibody and was partially blocked when PEC covered with anti-SRBC antibody were incubated with rabbit anti-guinea-pig globulin serum. Comparable amounts of anti-SRBC antibody injected separately had no enhancing effect. Anti-SRBC sera from which the cytophilic antibody activity had been removed were inactive. PEC-associated SRBC were usually more immunogenic than the same amount of `free' SRBC for the induction of delayed hypersensitivity and always more immunogenic for antibody production.

These observations suggested that macrophage cytophilic antibody might be involved in the regulation of the immune response and play a role in the preferential induction of delayed hypersensitivity in the studied system.

     

Cashew allergy: observations of 42 children without associated peanut allergy

BACKGROUND: Cashew allergy seems to be increasingly frequent. The goal of the present study was to analyse the clinical features and results of investigations of 42 children with cashew allergy. METHODS: The clinical features and results of skin prick tests, specific IgE assays, and food challenges were analysed. RESULTS: The mean age at first allergic reaction was 2 years and the mean age at diagnosis of cashew allergy was 2.7 years. One in five children (12%) had a prior history of exposure to cashew nuts. Fifty-six per cent had skin symptoms, 25% had respiratory signs and 17% had digestive signs. Eighteen children had proven, associated food allergies (pistachio, seven; egg, five; mustard, three; shrimp, two; cow milk, one). The mean wheal diameter of the skin prick tests was 7 mm (3-16 mm) and the mean specific IgE level was 3.1 kUA/L (<0.35->100 kUA/L). Eight children had positive food challenges. CONCLUSION: The increase in cashew allergy is worrying because it affects young children who may have a reaction without ever having been exposed to cashews. Almost one-third of children are allergic to pistachios, which belong to the same botanical family as cashews. Clinical history is generally and sufficiently suggestive to diagnose cashew allergy without recourse to food challenges.     

Renaissance of the blocking antibody concept in type I allergy

Formation of IgE antibodies against per se harmless antigens (i.e. allergens) is the hallmark and key pathomechanism of type I allergy, a hypersensitivity disease affecting more than 25% of the population. Classical experiments performed more than 65 years ago demonstrated that allergen-specific IgG antibodies, termed blocking antibodies, can antagonize the cascade of allergic inflammation resulting from allergen recognition by IgE antibodies. However, controversial results have questioned the protective role of IgG antibodies in allergic diseases. Here, we review recent data demonstrating that blocking antibodies inhibit allergen-induced release of inflammatory mediators from basophils and mast cells as well as IgE-facilitated allergen presentation to T cells, thus leading to suppression of T cell activation. Furthermore, it has been reported that the development of blocking antibodies is associated with reduced boosts of allergen-specific IgE production in patients receiving allergen-specific immunotherapy. These findings suggest that blocking antibodies have protective activity by inhibiting immediate as well as late inflammatory responses and long-term ameliorating activity on the allergic immune response by antagonizing the underlying IgE production. Induction of blocking antibodies is thus an important mechanism underlying allergen-specific immunotherapy. In addition, passive administration of blocking antibodies may be considered as a potential therapeutic strategy for allergic diseases.     

Absence of demonstrable phospholipid turnover in B cells stimulated by low mitogenic concentrations of dextran-anti-immunoglobulin conjugates.

Previously we have demonstrated that when anti-immunoglobulin (Ig) is conjugated to high molecular weight dextran (Dex) it stimulates B cell activation at pg/ml concentrations in the absence of detectable phosphoinositide hydrolysis or increases in intracellular ionized calcium. To study carefully whether anti-Ig-Dex recruited a phosphoinositide-dependent pathway of activation, we stimulated B cells that were labeled with 32P and [3H]glycerol with anti-Ig-Dex conjugates at concentrations ranging from 1-1 x 10(-4) micrograms/ml. Thirty seconds to thirty minutes after stimulation lipids were extracted and analyzed by thin layer chromatography and spots correlating with known lipid standards were isolated and counted. There was a four- and tenfold increase in the ratio of 32P/3H incorporated into phosphatidic acid (a metabolite of diacylglycerol) and phosphatidylinositol, respectively, when cells were stimulated with 0.1-1.0 microgram/ml of anti-Ig-Dex for 30 min. Below 1 ng/ml there was no detectable increase in the turnover of these metabolites despite the fact that in parallel cultures B cells were stimulated to proliferate by this concentration of anti-Ig-Dex. To determine whether a cAMP-dependent pathway was recruited by low concentrations of conjugates, we evaluated cAMP levels from B cells that were stimulated with anti-Ig-Dex for 5-60 min using a radioimmunoassay. While cholera toxin stimulated a 50-100-fold increase in the levels of cAMP, we observed no alteration in cAMP in anti-Ig-stimulated cells. These results support and extend our previous findings by demonstrating that B cell activation that is induced by cross-linking of surface Ig may not stimulate phosphoinositide-dependent or cAMP-dependent pathways of activation. Possible alternative mechanisms of activation will be discussed.     

An improved method for detection and titration of antibodies cytophilic for macrophages

A new microtechnique for detection and titration of antibodies cytophilic for homologous macrophages is introduced and experiments designed to determine the optimum conditions for its performance reported. The technique employs a series of small chambers formed on a microscope slide by the application of a plastic film in which holes have been punched. The procedure uses 5 x 10⁴ cells and 25 μl of serum per chamber, and each test can be completed in 2 h. A permanent preparation results which can be examined as and when convenient.     

Occupational type I allergy to Christmas cactus (Schlumbergera)

The study aimed to determine whether occupational contact urticaria and symptoms of mucous membranes, reported by five workers in a cactus nursery, were due to IgE-mediated allergy to Schlumbergera cacti. The five persons had positive skin prick tests to the plants as is and positive histamine-release tests, and in three of them specific IgE to the cacti could be demonstrated by Maxisorp RAST and immunoblotting. Four of the patients were atopic, and the fifth had a positive skin prick test to cat dander, indicating latent atopy. Skin prick tests with cacti were negative in most atopic volunteers, and all had negative histamine-release tests. The results suggest a true IgE-mediated allergy to the cacti, and both genetic predisposition and close contact with the plants at work seem to be important factors in the emergence of this new occupational allergy.