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[Immediate hypersensitivity in brucellosis. New data (author's transl)].

The presence of clinical manifestations of the "immediate hypersensitivity" process has been frequently described in veterinarians, bacteriological laboratory technicians and some patients with chronic brucellosis. We have looked for the presence of specific IgE in these conditions. Twenty-four patients, three months at least after the acute phase of their brucellosis, were given exploration of their humoral, cellular and specific immunity against brucellosis. For this purpose, beside usual classical tests: serodiagnosis, total and specific IgE assays, intradermoreaction and lymphoblastic transformation test with specific antigen (PI fraction) and an adaptation of human basophil degranulation test (HBDT) with PI fraction were performed on all 24 patients. Exploration of immediate hypersensitivity allows us to show neither an abnormal increase of hyper-IgE frequency nor an increase of anti-brucella specific IgE. HBDT is positive in 41 p. cent of the patients. It confirms that immediate hypersensitivity exists. HBDT gives justification for trying desensitization which has been proposed in the past. HBDT will possibly allow us to evaluate desensitization effectiveness.

Acute Disease↗

Immediate hypersensitivity in the guinea pig conjunctiva. III. long-term persistence of the hypersensitive state and characterization of antibodies.

The ocular immediate hypersensitivity reaction in guinea pigs to topically applied normal rabbit serum can be evoked as long as 4 years after sensitization. The reaction was as severe and tended to persist for longer than that evoked 6 months after sensitization. Passive cutaneous anaphylaxis tests showed that very high titres of homocytotropic antibodies were present and that both IgE- and IgG1-like antibodies were involved. Sensitization with one set of injections instead of two was not consistently successful and the response on challenge was mild to moderate. Pretreatment of eyes with Isoptocarpine before antigenic challenge had no effect on the response. The addition of bacterial lipopolysaccharide to the first set of sensitizing injections produced hypersensitivity in animals which were otherwise refractory to sensitization.

Animals↗

Mechanisms for glucocorticoid inhibition of immediate hypersensitivity reactions in rats.

The inhibitory mechanisms of immediate hypersensitivity reactions by glucocorticoid (GC) were studied in rats. Homologous passive cutaneous anaphylaxis (PCA) mediated by IgE antibodies and cutaneous reactions caused by histamine, serotonin and leukotriene C4 were elicited at the same time in the same rats. Three kinds of GC, hydrocortisone, prednisolone and dexamethasone, inhibited all these reactions significantly. Although mediator-induced cutaneous reactions were inhibited transiently around 2 hours after GC administration, inhibition of PCA was more potent and lasted longer. A time lag seemed to be essential for both inhibitions. IgE antibody-mediated histamine release in vivo in the rat peritoneal cavity was also inhibited by GC administration significantly, and the inhibition was long lasting when compared to those of the mediator-induced cutaneous reactions. Tyrosine amino-transferase (TAT) activity in the rat liver increased significantly by GC administration, and the increased TAT activity was completely abrogated by simultaneous administration of 5 mg/kg of cycloheximide (CH). In the same experimental condition, although inhibition of histamine-induced cutaneous reaction by GC was completely abrogated, the inhibition of PCA elicited at the same time in the same rats was only partially attenuated. Furthermore, the same dose of CH little affected the dexamethasone inhibition of histamine release in the rat peritoneal cavity, although the increase of TAT activity in the liver of the same rats was completely abrogated. These results demonstrate that PCA is inhibited by GC through at least 2 mechanisms, inhibition of mediator release from mast cells and non-specific inhibition of vascular permeability increase caused by released mediators. Although the latter action of GC is dependent upon protein synthesis, the former seems to be mediated by a unique mechanism independent of protein synthesis.

Animals↗

Immediate hypersensitivity phenomena in bullous pemphigoid: critical concepts.

The immediate hypersensitivity phenomena in bullous pemphigoid (BP) will be discussed in this review. There is prominent involvement of eosinophils in the pathogenesis of human BP. Activation of these eosinophils in BP may lead not only to tissue damage, but also to regulation of the immune response. Stimulation of Th2 cells is responsible for the production of IgG4 and IgE autoantibodies to the hemidesmosomal proteins, 180-kDa BP antigen and 230-kDa BP antigen.

Autoantibodies↗

Immediate hypersensitivity to quinolones: moxifloxacin cross-reactivity.

INTRODUCTION: Immediate hypersensitivity reactions to quinolones are rare. Moxifloxacin is an quinolone chemically different from other fluoroquinolones. We report 6 patients diagnosed with hypersensitivity to different fluoroquinolones in whom the response to moxifloxacin and cross-reactivity with other quinolones was studied. MATERIAL-METHODS: An allergenic study was made by prick and intradermal test with different fluoroquinolones, in all the patients. Single blind oral challenge tests were performed with moxifloxacin in all the patients, with ciprofloxacin in five patients, with levofloxacin in three patients and with ofloxacin in one patient. RESULTS: The skin test performed with moxifloxacin was positive in five patients, and the oral challenge test was positive in all six patients. All the patients had at least one positive skin test with some of the other fluoroquinolones. CONCLUSION: The skin test with different quinolones seems to be sensitive at showing group hypersensitivity, but not at predicting specific tolerance of each drug. We found a high degree of cross-reactivity among fluoroquinolones, so we currently recommend to avoid the group. We did not find that moxifloxacin differed from other fluoroquinolones so we cannot recommend it as a valid therapeutic alternative in patients sensitized to other quinolones.

Adult↗

A physiologic differentiation between delayed and immediate hypersensitivity.

Studies have been made of movement of various macromolecules into and out of the pleural space of guinea pigs during the course of a delayed hypersensitivity reaction to purified protein derivative (PPD), and a passively transferred immediate hypersensitivity reaction to ovalbumin. While the immediate hypersensitivity reaction transiently alters vascular permeability as shown by increased movement of macromolecules into the chest, the delayed hypersensitivity reaction is marked by a decreased capacity to resorb macromolecules from the pleural space. The data suggest that the two hypersensitivity reactions may be distinguished by these physiologic differences. Additional data from studies of a chemically induced pleural effusion in these animals suggest that some type of outflow obstruction is necessary for the development of effusion, but that the outflow defect caused by the irritating chemical is based on a different mechanism than that seen during the delayed hypersensitivity reaction.

Animals↗

Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B.

We investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA-reactive V beta 8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of V beta 8+ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen-specific IgE, decreased OVA-specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization of OVA, but shifted the immune response away from an immediate type response (IgE/IgG1) to IgG2a, IgG2b and IgG3. Although both protocols of SEB treatment did not lead to a major deletion of the V beta 8 T cell population, they did reduce the proliferative response of V beta 8+ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen-reactive V beta 8 T cells.

Allergens↗

STUDIES ON DELAYED HYPERSENSITIVITY. I. INFERENCES ON THE COMPARATIVE BINDING AFFINITIES OF ANTIBODIES MEDIATING DELAYED AND IMMEDIATE HYPERSENSITIVITY REACTIONS IN THE GUINEA PIG.

Experiments carried out with several well defined antigenic systems (hapten conjugates of poly-L-lysine and guinea pig serum albumin) in guinea pigs demonstrated that: 1. Arthus reactions also manifest carrier specificity, although to a smaller extent than do delayed hypersensitivity reactions. 2. Desensitization by injection of minute doses of antigen results in moderate specific desensitization of delayed hypersensitivity without desensitization of Arthus reactivity to the same antigenic determinant. 3. Insoluble antigen-antibody complexes prepared from high affinity guinea pig antibodies can elicit specific delayed skin reactions in sensitized guinea pigs. 4. Homologous conjugates of structurally similar haptens show considerably less cross-reactivity in delayed reactions than in immediate hypersensitivity reactions to the same antigenic determinant. These experimental results are interpreted as indicating that delayed hypersensitivity reactions in the guinea pig are mediated by "antibodies" of comparatively high binding affinities. High binding affinities are achieved for these antibodies more likely by closer structural adaptation between antigen and antibody than by a larger area of specific contact.

Animals↗

IgE and immediate hypersensitivity.

Tissue mast cells play a central role in immediate hypersensitivity reactions. The clinical manifestations of these reactions appear to be dependent, in large part, on the anatomic location of the stimulated mast cells and the type of mediators released. In vivo and in vitro studies indicate that the tissues in which mast cells reside may greatly influence their biochemical composition, expression of surface receptors, and response to potential stimuli. Although all human mast cells in different organs store similar concentrations of histamine, heparin, and tryptase, cutaneous mast cells appear to be the predominant source of mast cell-derived chymase. Furthermore, at the time of stimulation, human skin mast cells predominantly form PGD2, whereas lung and intestinal mast cells generate LTB4, LTC4, and PGD2. Functional studies indicate that human cutaneous mast cells differ from human lung, heart, and intestinal mast cells. Skin mast cells are responsive to a variety of immunologic and nonimmunologic stimuli in vitro, whereas human pulmonary, cardiac, and intestinal mast cells are relatively refractory to many of these stimulatory signals. Taken together, these observations indicate that mast cells may assume different, and possibly specialized, functions within a specific tissue. Such site-to-site variation potentially could have important clinical significance, to the extent that information gained from mast cells in one organ may not be applicable to a mast cell population in a different tissue. Furthermore, these differences among human mast cells may not be confined to their biochemical composition and responses to various stimuli, but also may extend to the effectiveness of different anti-allergic preparations. Therefore, these observations underscore the importance of continued detailed investigation of human mast cells from different anatomic sites.

Humans↗

Immediate hypersensitivity responses in the immunopathogenesis of human onchocerciasis.

It is not clear what role immediate hypersensitivity immune responses have in the pathogenesis of human onchocerciasis, but it is certain that these responses are prominent both in the course of natural infection and during the Mazzotti reactions that follow treatment with diethylcarbamazine. In humans, the levels of total serum IgE associated with onchocerciasis are as high or higher than those associated with almost any helminth infection, although specific IgE antibodies to Onchocerca volvulus appear to be a small and still poorly characterized fraction of the total serum IgE. Evidence about the relationship of these prominent IgE responses in patients with onchocerciasis to the onchocercal skin disease that manifests as pruritus and papular eruptions is conflicting, but in a guinea pig model of ocular pathology induced by onchocerca microfilariae evidence for the pathogenetic importance of IgE and immediate hypersensitivity is much less equivocal. The suggestive findings from this model make it imperative to carry out similar studies of Onchocerca-affected human eyes to determine whether immediate hypersensitivity responses play a similar critical role in the pathogenesis of the ocular lesions in humans.

Animals↗

Immediate hypersensitivity in the guinea pig conjunctiva intravitreal and topical sensitization.

The right eyes of guinea pigs were injected with 1.5 mg sterile ovalbumin. Two months later, one drop of ovalbumin (approximately 0.6 mg) was applied to the conjunctiva of both eyes. All challenged eyes developed an immediate hypersensitivity reaction within 5 min. The reaction subsided within 2 hrs. Prechallenge antibody titers, as determined by passive hemagglutination, passive cutaneous anaphylaxis, and by an ELISA test were low. Titers rose rapidly after two conjunctival applications at weekly intervals. The hypersensitivity reaction was elicited each time antigen was applied to the conjunctiva of the intravitreally sensitized guinea pigs. Control guinea pigs received weekly conjunctival application of ovalbumin, without prior intravitreal sensitization. Most animals developed an immediate hypersensitivity reaction following the fourth application of the antigen. There was no detectable hemagglutinating or ELISA (IgG1, IgG2) antibody at the time the conjunctival reaction was first elicited. These experiments demonstrated that high circulating IgG1 or IgG2 antibody is apparently not necessary to initiate an immediate hypersensitivity reaction in the guinea pig conjunctiva. The authors also demonstrated that weekly topical application of ovalbumin sensitized guinea pigs for immediate hypersensitivity.

Administration, Topical↗

Evaluation of E-721B, an indigenous herbal combination in experimental models of immediate hypersensitivity.

E-721B, an indigenous herbal combination was investigated for its usefulness in immediate hypersensitivity using different animal models. The drug inhibited the mast cell degranulation induced both by antigen and compound 48/80, the Schultz-Dale response in sensitized guinea pig ileum smooth muscle preparation and the production of precipitating antibodies in 50% of tested rats. It also inhibited the mast cell degranulation in passively sensitized rats indicating its suppressive action on production of reaginic antibody (IgE). However, the drug did not inhibit the 48 hours passive cutaneous anaphylaxis reaction in rats, indicating that a single dose of the drug does not have cromoglycate like properties. All the above results indicate the inhibitory effect of E-721B on immediate hypersensitive reactions such as asthma.

Anaphylaxis↗

Immediate hypersensitivity gastropathy and duodenogastric reflux.

The purpose of the present study was to define a correlation between immediate hypersensitivity gastropathy and duodenogastric reflux. The gastric mucosa can often be involved in immediate hypersensitivity reactions, mainly in atopic subjects suffering from other allergic diseases. The typical endoscopic findings concern alterations of the gastric mucosa, like pomphi and variolae, and alterations of the gastric motility, like spasms and pyloric disturbances, all of them occurring in the antrum in most cases. Histology and immunofluorescence show peculiar patterns. Bile reflux is present in over 50% of these patients. The possible relationship between duodeno-gastric reflux and the gastric hypersensitivity reactions is briefly discussed in the light of what is known about the action of bile on the gastric barrier.

Bile Acids and Salts↗

Modification of immediate hypersensitivity responses by staphylococcal enterotoxin B.

The staphylococcal enterotoxins have been termed superantigens based on their ability to stimulate polyclonal proliferative responses of murine and human T lymphocytes expressing particular T-cell receptor V beta gene products. Certain of these toxins have been shown both to activate and to induce anergy in reactive T cells. Staphylococcal enterotoxin B is known to interact with murine T cells bearing V beta 3, -7, -8.1, -8.2, -8.3, and -17. In BALB/c mice V beta 3+ and V beta 17+ T cells are deleted; V beta 7+ T cells are low in frequency. BALB/c mice sensitized to ovalbumin via the skin and airways develop immediate hypersensitivity including IgE/IgG1 antiovalbumin antibodies, immediate cutaneous reactivity to ovalbumin and, increased airway responsiveness. In both in vitro and in vivo studies, the development of these responses has been associated with the V beta 8+ subset of T cells and controlled by V beta 2 + T cells. In view of the central role of V beta 8+ T cells in these responses, we tested the effects of staphylococcal enterotoxin B on the development of immediate hypersensitivity in this system. Intradermal injection of staphylococcal enterotoxin B prevented the development of these responses in the absence of a major deletion of V beta 8+ T cells. The data suggest that the administration of staphylococcal enterotoxin B prevented the antigen-induced expansion of V beta 8+ T cells resulting in a state of responsiveness or anergy, thus preventing the manifestations of immediate hypersensitivity. Bacterial toxins may provide a novel approach to intervention in allergic or autoimmune diseases.

Allergens↗

[Characteristics of etiology of immediate hypersensitivity in conditions of exposure to infrasound].

The development of immediate hypersensitivity is process strictly specific for given allergen. The reaction with fatal outcome in guinea pigs is reproduced by 80-100%. However, the work has been published recently in which an opportunity to influence the effect of antigen by non-ionizing physical factors was considered. In experiments with 230 guinea pigs the model anaphylactic shock was used. Animals were subjected to infrasound of 10 Hz frequency and 155-160 dB intensity for ten minutes just before antigen introduction. About 50-60% of animals were wrecked under combined sensitizer and infrasound influence. At the same time in control experiments 80-100% of animals were wrecked three minutes after introduction of permitted dose of sensitizer. The experiments under changed conditions as well as series with passive sensitization have shown that the infrasound effect is due to deviations (rejections) in specific part of anaphylactic shock.

Anaphylaxis↗