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A comparison between streptokinase/streptodornase and streptokinase on delayed hypersensitivity skin testing.

The use of streptokinase (SK) to replace streptokinase/streptodornase (SK/SD) in delayed hypersensitivity skin testing was evaluated in 325 patients. Sixty patients responded to SK/SD (100 U of SK per 25 U of SD) and 36 to SK (375 U). Thirty-two responded to SK/SD but not to SK, and eight responded to SK but not to SK/SD. SK, at the dosage used, is not a suitable substitute for SK/SD in delayed hypersensitivity testing. SD may be the more potent recall antigen. Perhaps more importantly is that of 250 positive responders to a recall-antigen battery consisting of SK/SD, SK, Candida, Trichophyton, tetanus toxoid, purified protein derivative, and coccidioidin, 99.2% (248) would have been detected had the testing for SK and SK/SD not been done.

Adult↗

[The effect of 2-methyl-4-amino-6-hydroxypyrimidine on delayed hypersensitivity].

The effect of the immunomodulator 2-methyl-4-amino-6-oxypyrimidine (MAOP)on delayed hypersensitivity was studied in experiments on mongrel mice and in C57Bl and CBA mice. The effect of MAOP and that of oxymethyluracil on delayed hypersensitivity to sheep erythrocytes and dinitrofluorobenzene were compared. Immunosuppression of mice was induced by hydrocortisone in a dose of 50 mg/kg.

Adjuvants, Immunologic↗

Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage.

The role of delayed hypersensitivity in the pathogenesis of Chlamydia t trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayed-type hypersensitivity reaction was observed, characterized by mononuclear cell infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study showed that C. trachomatis infection in monkeys induced delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma.

Animals↗

Recurrent condylomata acuminata: how routine immediate and delayed hypersensitivity parameters might provide a clue to their immunopathogenesis.

In 30 male patients suffering from recurrent condylomata acuminata, immediate hypersensitivity parameters (total IgE, PTT and prick tests) and delayed hypersensitivity against seven recall antigens (multi test) were studied. Thirty healthy male volunteers, matched in age, were the controls. Significantly higher immediate hypersensitivity activity was shown in the patient group. Qualitative evaluation of delayed type hypersensitivity showed that controls had a positive test 16 times more often than patients. A rather homogeneous suppression of delayed type hypersensitivity was found in the patient group mainly as regards the presumably most common antigens vs. the control group. This suppression was proved to be related to disease duration. The hypothesis of a CD4+ Th-2 lymphocyte predominance in recurrent condylomata, owed to longstanding or repetitive antigenic stimulation seems to adequately explain the findings of the present study.

Adult↗

1976 Davis & Geck surgical essay. The delayed hypersensitivity response: clinical application in surgery.

The detection of anergy or relative anergy by delayed hypersensitivity skin tests was predictive of infection and related mortality in 354 surgical patients. Cancer or advanced age alone did not account for the increased morbidity and mortality seen in this study. Altered delayed hypersensitivity response is a reflection of abnormalities in cell-mediated immunity and possibly humoral or phagocytic defects, or both. Skin testing is of value to the clinical surgeon both in identifying the population at risk and in monitoring the immune response to therapy in the seriously ill patient. Failure to improve skin-test response may indicate underlying infection or malnutrition, which, if untreated, results in a high mortality.

Adolescent↗

Specific suppression of delayed hypersensitivity skin reactions to collagen in guinea-pigs after immunization with collagen and Freund's incomplete adjuvant.

Partial suppression of cutaneous delayed hypersensitivity reactions to collagen in guinea-pigs was induced by pre-immunization with collagen and FIA. This suppression is specific since: (a) pretreatment with OA and FIA or FIA alone did not cause suppression of skin reactions to collagen; (b) suppression was observed only if the collagen used for pretreatment was from the same species as that employed for sensitization for delayed hypersensitivity reactions; and (c) animals with depressed skin reactivity to collagen reacted normally to PPD. The suppression is not mediated by inducible, circulating antibodies to collagen since: (a) antibody titres measured by passive haemagglutination did not correlate with the degree of suppression; (b) suppression was observed with collagen in random coil conformation which sensitizes guinea-pigs for delayed hypersensitivity skin reaction but does not induce antibodies to denatured collagen; (c) best suppression was obtained if the animals were pretreated with collagen and FIA 3 days before the sensitizing injection; and (d) passively transferred antibody from animals with suppressed skin reactivity did not suppress skin reactivity of animals made hypersensitive to collagen by injection of collagen and FCA.

Animals↗

Delayed hypersensitivity in tumor-bearing mice. In vitro activation of "eclipsed" spleen cells.

At various stages during the progressive growth of a transplanted sarcoma in BALB/c mice, the delayed hypersensitivity response to tumor antigen was determined using the food-pad swelling test (FPS) and the leukocyte migration inhibition assay (LMI). A close correlation was observed between the in vivo and in vitro assays. "Early" recognition of tumor antigen was detected 24 h after tumor inoculation by both techniques and this positive response was maintained until day 15. As the tumor grew larger, the delayed hypersensitivity response in vivo vanished, while the delayed hypersensitivity response in vitro disappeared about 3 days later. This suppression or "eclipse" of the anti-tumor cellular immune response was specific for the type of tumor used, and could be reversed in vitro by means of a low pH treatment of lymphoid cells.

Animals↗

Evaluation of delayed hypersensitivity: from PPD to poison ivy.

Intact cell mediated immunity (CMI) requires a complex interaction between lymphocytes, macrophages, and cytokines. The presence of functional CMI can be easily tested in vivo by delayed hypersensitivity (DTH) skin testing. Delayed hypersensitivity skin testing has been commonly used in three ways; anergy screening, testing for infection with intracellular pathogens, and testing for sensitivity to contact allergens. Accurate anergy screening requires intradermal testing with four or more common recall antigens such as Candida albicans, tetanus toxoid, mumps, and purified protein derivative. Problems of antigen potency and availability can be overcome by using a multiple time test-like device that contains seven different recall antigens (Multitest CMI). Although testing for infection was once common, it is now only recommended for tuberculosis screening because most other antigens are either not predictive of infection or not commercially available. Accurate testing for contact allergy requires careful attention to technique, and limitation of allergens to the 20 antigens that are approved by the American Academy of Dermatology.

Allergens↗

Delayed hypersensitivity reactions in patients with acute leukemias and blastic crisis of chronic granulocytic leukemia.

Delayed hypersensitivity reactions were studied in 34 patients with acute leukemias and 13 patients in blastic crisis of chronic granulocytic leukemia during the course of the disease. All patients were skin tested with PPD, Candida antigen, SK/SD and DNCB. A positive correlation existed in majority of patients between the response chemotherapy and delayed hypersensitivity reactions in the tested patients.

Acute Disease↗

Cutaneous delayed hypersensitivity in patients with colorectal cancer: application of multi-test.

A prospective study of delayed hypersensitivity was carried out in 63 colorectal cancer (CRC) patients of good nutritional status and 63 healthy controls over a period of 3 years. Delayed hypersensitivity was assessed by application of Multi-test which involves synchronous multiple puncture testing with seven antigens. Subjects were classified in three groups: Immunocompetent, Relatively anergic and Anergic. Logistic regression analysis was applied. The patients had lower mean scores for skin reactions to all tested antigens with the widest differences observed for Trichophyton. The average number of positive reactions was lower for patients than controls; there were no anergic subjects among the controls and the differences between patients and controls were statistically significant. Patients with early disease (Dukes' A and B), had lower scores for all seven antigen reactions than controls, but higher than those with advanced disease. Differences between early stage cases and controls were not statistically significant for any antigen, nor for the total number of positive reactions or the total score. In the late stages of their disease patients with CRC and without malnutrition, or any other kind of acquired immunodeficiency, have impaired cellular immunity in comparison with normal controls.

Adult↗

Suppression of delayed hypersensitivity in vitro by inhibition of protein synthesis.

Peritoneal cells from guinea pigs exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is prevented by the addition of puromycin to the culture medium. The amount of puromycin necessary to prevent the inhibition by antigen also suppressed the incorporation of C(14)-leucine into peritoneal cell protein. Additional evidence that the action of puromycin is due to its inhibition of protein synthesis has been obtained with analogues of puromycin; those that inhibit protein synthesis also prevent the action of antigen on the cells, while those analogues that do not inhibit protein synthesis have no effect. Actinomycin also prevents the inhibition of sensitive cells by antigen while chloramphenicol has no effect. The data indicate that the inhibition of sensitive cell migration by antigen requires active protein synthesis. The possible mechanisms by which inhibition of protein synthesis may influence the in vitro reactions of delayed hypersensitivity are discussed.

Animals↗

Endothelial proliferation in the delayed hypersensitivity reaction: an autoradiographic study.

The time-sequence of endothelial proliferation in the delayed hypersensitivity reaction was examined in the skin of guinea pigs. Animals were sensitized to tuberculin (PPD) and dinitrochlorobenzene (DNCB) and skin lesions were examined 12 hr to 7 days after challenge. Thirty minutes before sacrifice 3H-thymidine (3H-T) was injected i.p. and endothelial labeling was assessed in autoradiographs of 1.5-mu thick methacrylate sections. Endothelial labeling became manifest at 24 hr (PPD) and 12 hr (DNCB) after challenge, reaching a peak at 48 to 72 hr in PPD-sensitized animals and 36 to 48 hr in DNCB-sensitized animals. Peak labeling indices were 7.88 and 15.08%, respectively. Labeling indices for nonsensitized control groups were always less than 1%. Endothelial labeling was associated, in time of occurrence, distribution, and magnitude with mononuclear cell infiltration of the lesions. These findings thus document the occurrence of significant endothelial cell proliferation in delayed hypersensitivity responses and suggest that the events leading to the expression of hypersensitivity also result in endothelial replication.

Animals↗

Sternotomy infection: poor prediction by acute phase response and delayed hypersensitivity.

Two hundred twenty-one consecutive adult cardiac surgical patients were examined prospectively for nutritional protein state, acute phase protein response, and delayed hypersensitivity reaction in an attempt to identify patients at high risk for the development of sternal wound infection, which occurred in 6 patients (2.7%). There was no significant correlation between preoperative nutritional protein concentrations (retinol-binding protein, prealbumin, and transferrin) and acute phase protein levels (C-reactive protein, alpha 1-acid glycoprotein, and complements B and C3), nor a statistically significant relationship between nutritional state or acute phase protein response and the development of sternal infection. Preoperative complement C3 levels were elevated, however, in 80.0% of those in whom sternal infections developed compared with 30.6% of those with well-healed wounds. Similarly, postoperative concentrations of alpha 1-acid glycoprotein were elevated in 80.0% of those in whom sternal infections developed compared with 28.6% of those with well-healed wounds. There was no correlation between delayed hypersensitivity and the risk of sternal infection, nor between preoperative nutritional protein and acute phase protein values. Seventy-three percent of patients were anergic on postoperative day 2. Stepwise logistic regression showed that age, body weight, preoperative intensive care unit stay, repeat median sternotomy, internal mammary artery grafting, postoperative hemorrhage, and postoperative cardiac arrest correlated with the development of sternal infection, whereas transfusion requirement, reexploration for bleeding, and the operation performed did not. We conclude that routine delayed hypersensitivity testing is of no value in predicting high-risk cardiac surgical patients when the anergy battery is placed on the preoperative day. Although statistically insignificant, possibly due to the small number of patients in whom sternal infection developed in this study (type II error), a larger study might find preoperative complement C3 and post-operative alpha 1-acid glycoprotein levels to be predictive of patients at risk for the development of sternal wound infection. The final logistic model for the predicted risk 2%) of sternal wound infection is: PREDSWC = exp(EQ)/1 + exp(EQ) where EQ = (0.38 x age) + (0.24 x weight) + (5.42 x preop ICU) + (4.39 x redo) + (7.14 x IMA) + (4.49 x hemorrhage) + (8.81 x arrest) - 62.72, and where preop ICU, redo, hemorrhage, and arrest are defined as yes (1) or no (0), IMA-is defined as 0, 1, or 2, age is in years, and weight is in kilograms.

Acute-Phase Proteins↗

Detection of delayed hypersensitivity in mice injected with ribonucleic acid-protein fractions of Salmonella typhimurium.

Manifestations of delayed hypersensitivity (cell-mediated immunity) were found to be present in mice immunized with virulent Salmonella typhimurium SR-11 subfractions which contained appreciable concentrations of bacterial protein and in mice immunized with the living, attenuated RIA strain of S. typhimurium. Delayed hypersensitive responses were measured by footpad sensitivity in the immunized mice and in vitro by inhibition of spleen cell migration and by increase in (3)H-thymidine uptake by lymphoid cell populations when exposed to bacterial fractions rich in protein content.

Animals↗

Delayed hypersensitivity skin tests in prognosis of human immunodeficiency virus infection.

Delayed hypersensitivity skin tests (DHST) with recall antigens were investigated as prognostic markers in five different approaches. In the first study, 42 acquired immunodeficiency syndrome (AIDS) patients (IVb, IVcl, IVd, and IVe; MMWR 35:334-339, 1986) 26 AIDS-related complex (ARC) patients (IVa and IVc2), and 98 asymptomatic patients (II and III) were evaluated with candidin, tricophytin, PPD and streptokinase-streptodornase. In the second study, 10 patients (II and III) were evaluated sequentially with the same antigens. In the third, 45 patients with at least two positive skin tests ("reactors") were followed for one year and evaluated every 6 months with the same antigens. In the fourth, 16 "reactors" were followed and evaluated every 3 months with the same antigens. We measured the interval from the time at which patients first presented with only one or no positive DHST until the development of ARC or AIDS. In the last study, the correlation between absolute number of CD4+ lymphocytes and the number of DHST was studied in 151 patients. We found that the decrease in reactiveness to DHST correlated directly with the progression to AIDS, demonstrating the usefulness of this simple procedure as a valid prognostic marker.

AIDS-Related Complex↗

Relationship of antimicrobial cellular immunity to delayed hypersensitivity in Listeriosis.

The relationship of antimicrobial cellular immunity to delayed hypersensitivity (DH) was studied in mice antigenically stimulated by living Listeria monocytogenes confined to diffusion chambers in peritoneal cavities or by subcutaneous inoculation of sublethal doses of the organism. Mice showed DH reactions when tested 6 days after inoculation, and reactions were positive for at least 90 days in some mice. DH also became established when the mice were stimulated by antigens diffusing from peritoneal chambers containing viable Listeria. Mice were categorized as DH positive or DH negative if they developed more or less than a 5% increase in foot volume 24 h after the injection of Listeria antigen. Some antigenically stimulated mice did not elicit the DH reaction. Consequently, the animals were arranged as immunized groups (DH positive and DH negative) and Listeria chamber implant groups (DH positive and DH negative). When challenged with L. monocytogenes, all four groups were significantly resistant as compared with controls. Thus, the in vivo tests for immunity and DH did not show direct correlation. The results suggested that antimicrobial cellular immunity can occur as a phenomenon independent of DH. Evidence for antimicrobial cellular immunity as the principle mechanism of resistance in murine listeriosis is discussed with consideration for possible heterogeneity of function by thymus-derived lymphocytes.

Animals↗