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Enhanced delayed hypersensitivity skin test reactivity with serial testing in healthy volunteers.

Delayed hypersensitivity skin testing with multiple antigens is frequently used to evaluate immunopotentiation therapy in man. Since serial skin testing with a single antigen has been shown to augment the skin test response, the present study was undertaken to assess the effect of serial delayed hypersensitivity skin testing on skin test reactivity with multiple antigens. Each of twelve healthy volunteers received 0.1 ml of five antigens on two occassion, 6 weeks apart. The antigens used were streptokinase-streptodornase, Candida, Trichophyton, mumps and Mycobacterium tuberculosis (PPD). The results demonstrated enhancement of skin test reactivity in the majority of tests. Indeed, 38.9% of the tests which were negative with the first skin test ( less than 10 mm induration) converted to positive. Enhancement in reactivity was observed in the majority of test subjects with all antigens except PPD. Similar enhanced skin test reactivity was observed in fifteen additional subjects tested serially with Candida only. The observations in this study suggest that uncontrolled studies of immunopotentiation must be interpreted with caution since serial delayed hypersensitivity skin testing with single or multiple antigens results in enhanced skin test reactivity.

Adult↗

Dose response relationships and interference of simultaneous skin tests in delayed hypersensitivity.

The relationship between the intensity of the delayed hypersensitivity reaction and the dose of antigen used for its elicitation change with time after sensitization. At three weeks the reactions to 100 mug of egg albumen were little different from those to 1 mug but at 14 weeks 100 mug gave much stronger reactions. This means that to follow the development of a delayed hypersensitivity response several antigen doses should be used. If two skin tests were performed simultaneously in the same individual, the stronger one suppressed the weaker one, regardless of whether two different doses of the same antigen or two different antigens were used. Consequently, not more than one skin test at a time should be performed.

Animals↗

[Delayed hypersensitivity to heparins and heparinoids].

Delayed hypersensitivity to heparins and heparinoïd is a problem for prophylaxis of thrombo embolic diseases. The hirudins did not seem to have any cross-reactivity with the two others groups of anticoagulants. We present two clinical cases of delayed type reactions to heparins and heparinoïd and we reviewed the literature about adverse reactions to low molecular weight heparins and the alternative possibilities.

Aged↗

Cutaneous-delayed hypersensitivity in nursing home and geriatric clinic patients. Implications for the tuberculin test.

Cutaneous-delayed hypersensitivity was studied by one and two-step Mantoux-type skin tests to four standard antigens in 33 elderly nursing home residents, 34 geriatric clinic patients, and 20 healthy young adult controls. Demographic and anthropometric data were collected to determine the effects of nutrition and other variables on cutaneous-delayed hypersensitivity. Anergy (a lack of response greater than 5 mm of induration when read at 48 hours) to any of the four antigens occurred in 34% of nursing home residents, 17% of geriatric clinic patients, and none of the healthy young adults. Mean and maximal responses were less in the nursing home residents than the clinic patients or controls, even if anergic individuals were excluded from analysis, suggesting both a qualitative and quantitative decline in cell-mediated immune function in this elderly population. Repeat testing with each antigen for which there was a negative initial response revealed a "booster" affect of 7 to 19% and occurred as commonly in the healthy young adults as in the nursing home residents or geriatric clinic patients. The mumps antigen elicited strong responses in the healthy young adults, but weak reactions in the nursing home residents. An unexpectedly high prevalence of positive tuberculin (PPD) responses occurred in the nursing home residents, suggesting recent exposure. Analysis of anthropometric and demographic characteristics show that neither nutritional status nor age alone can account for differences in cutaneous-delayed hypersensitivity observed between populations. Cutaneous-delayed hypersensitivity may vary widely between elderly populations and have important practical implications for the tuberculin test.

Adult↗

Requirements for inducing tolerance of hapten-specific delayed hypersensitivity: epitope density.

Tolerance to hapten-specific antibody formation and delayed hypersensitivity was examined in adult rabbits. The azobenzenearsonate (ABA) or sulfonate-specific antibody response to hapten-hemocyanin immunogens was suppressed by deaggregated hapten-rabbit IgG conjugates given 21 and 14 days before challenge. High affinity antibody was preferentially suppressed. Delayed hypersensitivity to ABA-tyrosine was suppressed by deaggregated ABA-rabbit IgG conjugates injected 17 and 10 days before challenge. Conjugates with a high hapten density, ABA15-23-rabbit IgG were effective tolerogens. Conjugates with four to six ABA groups per carrier molecule were very poor tolerogens. Increasing the amount of low substituted conjugate injected did not improve tolerogenicity. It appears that a high epitope density is required for effective induction of tolerance to ABA-specific delayed hypersensitivity in the rabbit.

Animals↗

Polysaccharide in delayed hypersensitivity. I. Pneumococcal polysaccharide as inducer and elicitor of delayed reactivity in guinea pigs.

A highly purified pneumococcal polysaccharide (Type II SSS) is a very efficient inducer of delayed hypersensitivity in random-bred guinea pigs. The cellular reactivity induced by this polysaccharide administered subcutaneously in complete Freund's adjuvant is of "tuberculin type"; it increases in intensity with time after the sensitizing injection, as judged by skin tests, the macrophage inhibition reaction and transfer of reactivity by peritoneal exudate cells. By contrast, the cellular reactivity induced by this immunogen in the absence of mycobacterial adjuvant has the characteristics of "Jones-Mote" reactivity. It is best seen at about 1 wk after sensitization; the reactions are characteristically little indurated and show histologic differences from tuberculin type responses; and the reactive state begins to disappear by 2-3 wk, with the accession of Arthus reactivity. This type of delayed reactivity may be related to an early phase of antibody synthesis.

Animals↗

Quantitative measurement of delayed hypersensitivity in the guinea pig paw.

To facilitate quantitative measurement of a delayed hypersensitivity reaction, a tuberculin reaction was produced in the paws of sensitized guinea pigs and the resulting edema estimated by one of the usual techniques. The edema formation was shown to be an expression of the delayed hypersensitivity reaction. Optimal conditions for this reaction were assessed. This model may be used for testing the influence of drugs on delayed hypersensitivity reactions.

Animals↗

ANTIGEN-ANTIBODY REACTION: NATURE OF COMPLEX INITIATING DELAYED HYPERSENSITIVITY.

Two homologous lightly coupled dinitrophenyl conjugates of poly-L-lysine of differing average molecular sizes were compared with regard to their abilities to elicit in guinea pigs specific delayed hypersensitivity skin reactions, passive cutaneous anaphylaxis, and active Arthus reactions. Equal concentrations by weight (but not equimolar concentrations) of the two conjugates elicited equally intense delayed hypersensitivity reactions and Arthus reactions, whereas equimolar concentrations (but not equal weightconcentrations) elicited equally intense passive cutaneous anaphylaxis reactions. These results suggest that delayed hypersensitivity reactions are initiated by the reaction of antigen with antibody molecules in true solution, and not by the simple bridging by antigen of a small number of antibody molecules firmly fixed to cell membrane surfaces. Whether "sensitized cells" or circulating "delayed hypersensitivity antibodies" are the specific mediators of the delayed hypersensitivity reactions is discussed.

Anaphylaxis↗

Transfer factor: delayed hypersensitivity to Schistosoma mansoni and tuberculin in Macaca mulatta.

Delayed hypersensitivity in Macaca mulatta infected with either Schistosoma mansoni or mycobacteria was demonstrated by biopsies of skin test sites. Both dialyzable and nondialyzable leukocyte extracts from infected donors transferred delayed hypersensitivity to recipient monkeys. In two recipients, skin test conversion was associated with in vitro transformation of the recipients' lymphocytes.

Animals↗

The adjuvant activity of mycobacterial RNA preparations and synthetic polynucleotides for induction of delayed hypersensitivity to purified protein derivative in guinea pigs.

The adjuvant activity of mycobacterial RNA and synthetic polynucleotides for the induction of delayed hypersensitivity to PPD was determined. It was shown that when mycobacterial RNA or synthetic polynucleotides are injected together with purified protein derivative (PPD), delayed hypersensitivity to PPD developed as compared to no detectable delayed response when PPD was administered alone without adjuvant into guinea pigs. Four different criteria were employed to detect delayed hypersensitivity responses. These were the time, appearance, and magnitude of dermal reactions, histologic examination of dermal sections, passive transfer of sensitivity with sensitized spleen cells and the elaboration of migration inhibitory factor (MIF) by sensitized spleen cells. When synthetic polynucleotides were used as adjuvants and were injected into guinea pigs in combination with PPD, dermal reactions as well ad MIF assays gave evidence that these animals exhibited delayed-type hypersensitivity. Poly U alone exhibited adjuvant activity for induction of delayed hypersensitivity to PPD. Trypsin and pronase treatment did not affect the adjuvant activity of mycobacterial RNA whereas KOH treatment completely abolished any adjuvant effect, suggesting that ribosomal protein did not contribute to the adjuvant characteristics of mycobacterial RNA. Titration experiments indicated that the adjuvant activity of mycobacterial RNA was greater than that of poly A:U.

Adjuvants, Immunologic↗

The multitest system for delayed hypersensitivity evaluation. Standardized result in an Italian adult population.

Delayed hypersensitivity was evaluated by means of Multitest System in 50 healthy Italian adults. Results were checked for homogeneity, comparability and reliability assays. Strict antigen and technique standardization warranted closely homogeneous results. Booster effect did not occur. Data evaluation was not depending on individual reader. Multitest System appears to be the most reliable method to evaluate delayed hypersensitivity and cellular immunity in man.

Adult↗

Immune response to BCG-Moreau (Rio de Janeiro) strain. Spectrum of delayed hypersensitivity in genetically defined mice.

Generation of delayed hypersensitivity (DTH) in genetically defined mice immunized with Mycobacterium bovis BCG of the Moreau (Rio de Janeiro) strain was studied. This vaccine strain has been reported as the most virulent and able to induce strong tuberculin sensitivity. Mice were selected by the expression of Bcg gene trait, by responsiveness to mycobacterial antigens and H2 haplotype. DTH was evaluated by the ear-swelling test of mice immunized subcutaneously with live BCG at doses ranging from 1 microgram to 1000 micrograms. A survey of inbred strains of mice showed H2b and H2q mice as high responders, H2d as an intermediate responder, H2k as a low responder and H2a as a non-responder. Study of H2-congenic pairs of high and non-responder strains showed significant DTH in all mice independently of the genetic background and H2 haplotype. A mouse strain expressing Bcg (r) trait displayed DTH superior to a Bcg (s) strain. Comparison of DTH response of strains expressing Bcg (r) or (s) trait showed no relationship between the Bcg locus and DTH to mycobacteria. These data suggest DTH is under polygenic control including the major histocompatibility complex but excluding the Bcg locus.

Animals↗

Selective suppression of granuloma formation and delayed hypersensitivity in rabbits.

The relationship between dermal delayed hypersensitivity (DH) and granulomatous hypersensitivity was studied in rabbits sensitized with killed mycobacteria. Specific antigen challenge of sensitized animals resulted in extensive pulmonary granulomatous inflammation and induced suppression of both dermal DH and dermal granuloma formation. Whereas suppression of DH was concomitant with pulmonary granuloma formation, as is the case in a number of granulomatous diseases, a causal relationship between the two did not exist. Both DH and dermal granulomatous hypersensitivity were significantly suppressed whether or not the antigen challenge was of a granulomagenic (particulate) or nongranulomagenic (soluble) form. The data presented indicate that granulomatous hypersensitivity and DH are selectively suppressed with regard to different anatomical sites.

Animals↗

Delayed hypersensitivity reactions following allergic and irritant inflammation.

Delayed hypersensitivity retest reaction 3 and 6 weeks after induction of allergic and irritant inflammation, was studied in 13 females with known hypersensitivity to nickel. An increased retest reaction compared to controls was observed only in sites of earlier specific allergic inflammation. Also a general down-regulation of the degree of hypersensitivity was observed at retesting.

Adult↗

Partial purification of antigens from eggs of Schistosoma mansoni that elicit delayed hypersensitivity.

Schistosoma mansoni egg antigens that elicit delayed hypersensitivity in appropriately sensitized guinea pigs were partially characterized by using ion exchange chromatography and preparative electrophoresis. At least three skin-reactive antigens were found, one of which was purified to homogeneity, as analyzed by polyacrylamide gel electrophoresis (PAGE). This antigen was not adsorbed to CM cellulose, migrated cathodal to guinea pig albumin on electrophoresis, and was adsorbed to DEAE cellulose. A second pool of antigenic activity was obtained by adsorption to CM cellulose and subsequent elution. DEAE cellulose chromatography and preparative electrophoresis of this pool indicated the presence of more than one antigen.

Animals↗

Value of delayed hypersensitivity index in patients with malignancy.

A delayed hypersensitivity index can be obtained by standardized in vivo testing with available antigens. Recall antigens and DNCB to measure the afferent limb can be used to assess this important body function. The index is a valid indicator of cellular immunity, which is important as a dynamic indicator in many medical conditions and in treating patients with malignancy.

Candida↗

Suppression of delayed hypersensitivity to tuberculin by antigenic competition. A positive immunoregulatory mechanism sensitive to cyclophosphamide.

Effector mechanisms that produce delayed hypersensitivity reactions to tuberculin are subject to positive immunoregulation. Two different immunoregulatory mechanisms can be demonstrated. One is specific and the other, antigenic competition, is non-specific; both are sensitive to cyclophosphamide (CY). Delayed hypersensitivity to purified protein derivative PPD in guinea-pigs can be enhanced by the administration of cyclophosphamide 3 days before but not after immunization. The enhanced response seems to result from the reduced influence on effector cells of CY-sensitive suppressor cells. Passive transfer of delayed hypersensitivity to PPD is facilitated by the use of cells from CY treated animals. The response to both immunization and skin testing with ovalbumin in animals immunized with this antigen in Freud's complete adjuvant (FCA) produces a marked, non-specific reduction in the delayed hypersensitivity response to PPD. CY given 3 days before or 1 day after immunization prevents this suppression of the PPD response by antigenic competition. The data suggests that in the generation of both the specific suppressor cells for tuberculin and the non-specific suppressor cells of antigenic competition, that can influence effector cells for tuberculin, a period of rapid cell proliferation occurs that renders both mechanisms sensitive to cyclophosphamide.

Animals↗

Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality.

Delayed hypersensitivity skin reactions to a battery of recall antigens, haemoglobin and albumin concentrations, arm-muscle circumference, and percentage of ideal weight were determined before operation in 244 patients undergoing elective major surgery. Depressed skin reactions were found in 70 patients (28%), but this group did not have significantly higher sepsis or mortality rates when compared with patients with normal reactions. Significant associations were found between depressed skin reactions and increasing age, anaemia, hypoalbuminaemia, low arm-muscle circumference, and low weight. Patients with benign and malignant disease had similar distributions of skin reactions. Hypoalbuminaemia was associated with a higher rate of serious postoperative sepsis, and hypoalbuminaemia, low arm-muscle circumference, and low weight were all associated with a higher mortality. These results suggest that the routine use of delayed hypersensitivity skin testing in the preoperative assessment of surgical patients is not justified.

Abdomen↗