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PubMedDate not supplied

Delayed hypersensitivity skin testing in elective colorectal surgery and relationship to postoperative sepsis.

Delayed hypersensitivity skin testing to five common recall antigens (Varidase, Candida, PPD, Trichophyton, and Mumps) was performed on 50 patients undergoing elective colorectal surgery. Eighteen patients showed an altered response to skin testing (11 relative anergy, seven total anergy) and this group of patients had a significant increase in both total septic complications (p less than 0.001) and major septic complications (p less than 0.05) following operation. Anergy in these patients did not correlate with nutritional status, but it did relate to stage of the tumor in patients with cancer. The low specificity of abnormal delayed hypersensitivity skin testing and its failure to be related to malnutrition limits the practical application of this technique in patients undergoing elective colorectal surgery.

Adult↗
PubMed1980

Development of delayed hypersensitivity in gnotobiotic mice.

Germ-free mice develop low levels of delayed hypersensitivity following exposure to sensitizing doses of sheep erythrocytes, compared to that seen in conventionally raised mice. Infection of the germ-free animal with either Salmonella gallinarum or Salmonella pullorum was followed by extensive growth of the organisms within the intestine and the gut-associated lymphoid organs. As many as 5,000 viable Salmonellae were recovered from the cecal and ileal Peyer's patches as well as the mesenteric lymph nodes. However, neither strain spread significantly beyond the lymph nodes to the blood stream or to the liver and spleen. The gnotobiotic mice developed significant levels of delayed hypersensitivity to the Salmonella protein antigen and could be more readily sensitized to sheep erythrocytes than the germ-free host, despite the fact that Salmonellae were only able to infect the gut-associated lymphoid tissues.

Animals↗
PubMed1975

Modulation of the immune response by passive antibodies. I. Anti-hapten antibodies enhanced delayed hypersensitivity to the carrier and depressed antibody synthesis to the hapten.

The modulating effects of passive antibodies on both delayed hypersensitivity to the carrier and antibody synthesis to carrier and hapten determinants were studied in guinea pigs. Animals were injected with antibodies directed against either the carrier or the hapten prior to immunization with the hapten-carrier conjugate in Freund's complete adjuvant. Anti-hapten antibodies have been shown to have an enhancing effect on delayed hypersensitivity to the carrier and a suppressive effect on antibody synthesis to the hapten. In this experiment, anti-carrier anti-bodies seemed to have had no effect on delayed hypersensitivity to the carrier and on antibody synthesis to the hapten.

Animals↗
PubMed1973

Mechanisms in the suppression of delayed hypersensitivity in the guinea pig by 6-mercaptopurine.

The mechanism of suppression, of delayed hypersensitivity to tuberculoprotein by 6-mercaptopurine (6-MP) was studied in guinea pigs. Under the conditions of the protocol, suppression of tuberculin delayed skin test reactivity was not associated with a significantly altered end-organ response to mediators of permeability. No significant alteration of in vivo lymphoid activity, as measured by reconstitution studies, was found. In addition, lymphoid cells from 6-MP-treated animals reacted in a fashion similar to those of placebo-treated animals with respect to (a) antigen-induced lymphocyte proliferation, (b) antigen-induced liberation of macrophage inhibitory factor activity, (c) direct inhibition by antigen of peritoneal exudate cell migration. Conversely, suppression was seen in levels of blood monocytes and in vitro function of macrophages from 6-MP-treated animals in several respects: (a) adherence to glass, (b) migratory rate, (c) phagocytic capacity. Therefore, it would appear that a ma]or mechanism of 6-MP-induced suppression of delayed hypersensitivity is through its action on effector cells.

Animals↗
PubMed1975

Improvement in delayed hypersensitivity in Hodgkin's disease with transfer factor: lymphapheresis and cellular immune reactions or normal donors.

Passive transfer of delayed hypersensitivity was achieved, with normal transfer factor, in patients with Hodgkin's disease in remission. The cellular immune responses of the recipients improved. It is suggested that, in addition to specific effect the transfer factor (or factors) has a nonspecific effect causing improvement in the state of delayed hypersensitivity of the recipient in general. The average number of E-rosette T lymphocytes was 46.3% after the transfer factor treatment in Hodgkin's disease. The control patients with Hodgkin's disease, not receiving transfer factor, had a value of 37.8%. Removal of 4.9 X 10(9) to 1.08 X 10(10) lymphocytes did not diminish the delayed hypersensitivity of the donor. Side effects attributable to transfer factor were not seen.

Cell Count↗
PubMed1977

Delayed hypersensitivity in Graves' disease and exophthalmos: identification of thyroglobulin in normal human orbital muscle.

Patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity to antigens present in extracts of certain normal human tissue; namely,thyroid gland and retroorbital tissue. The delayed hypersensitivity can be assayed in vitro by quantitating the amount of a lymphokine, migration inhibition factor (MIF), which is produced when T lymphocytes of patients with Graves' disease and exophthalmos are exposed to these antigens. In the present report, a partial purification is described for the retro-orbital tissue antigen which is responsible for the positive leucocyte migration inhibition factor assay (MIF assay) exhibited by a sensitized lymphocytes of these patients. The purified retro-orbital tissue antigen preparation demonstrates a 50- to 150-fold higher specific activity over crude homogenates in its ability to act as an antigen in the MIF assay of exophthalmic patients. Immunodiffusion, ultracentrifugation, and disc electrophoretic data indicate that this purified antigen preparation, obtained from normal human, retro-orbital tissue, contains thyroglobulin or a derivative of thyroglobulin; immunofluorescence studies localize the anti-thyroglobulin reactive material to the plasma membranes of extraocular muscle fibers of normal individuals. On the basis of these data it is concluded that thyroglobulin or a derivative of the thyroglobulin molecule is present in the orbital muscle of normal individuals. Since thyroglobulin purified from normal human thyroid glands and the purified retro-orbital tissue preparation are nearly equivalent as antigens in the MIF assay of exophthalmic patients, we conclude that thyroglobulin or an antigenic component of the thyroglobulin molecule is one of the antigens to which patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity.

Antigens↗
PubMed1991

Early cellular events in evolving cutaneous delayed hypersensitivity in humans.

The delayed-type hypersensitivity reaction (DHR) in human skin is prototypic for many inflammatory dermatoses. However the cellular events that precede gross lesion formation are unknown. In this study, inflammatory cell populations and adhesion molecule expression in early phases of DHR elicited by 2,4-dinitrochlorobenzene were evaluated. The first discernible event (at 1 hour) was mast cell degranulation, followed by induction of endothelial leukocyte adhesion molecule (ELAM-1) expression on dermal postcapillary venules at 2 hours. Endothelial leukocyte adhesion molecule expression peaked at 24 hours and declined by 48 hours. In contrast, endothelial expression of intercellular adhesion molecule-1 (ICAM-1) remained at constitutive levels. Intrafollicular T-cell migration occurred independent of ICAM-1 expression and commenced as early as 4 hours after challenge. Mature, activated CD4-positive lymphocytes that expressed a helper-inducer/memory phenotype predominated in early lesions. These results demonstrate in vivo that mast cell degranulation, ELAM-1 expression, and memory T-cell-follicular interactions are key events in subclinical evolutionary stages of cutaneous DHR.

Adult↗
PubMedDate not supplied

[The effect of cholinergic substances on the development of delayed hypersensitivity].

The formation of delayed-type hypersensitivity (DTH) to ram erythrocytes was studied in BALB/c mice on different models during cholinergic stimulation induced by armin (0.3 mg/kg) and a M-cholinolytic atropine (50 mg/kg). The relationship between the formation of this reaction and the contents of T-lymphocytes and T-suppressors in the spleen and peripheral blood was also investigated. When administered one hour before immunization by ram erythrocytes, armin was shown to reduce the formation of DTH. Under the same conditions atropine failed to influence DTH reaction. In the local adoptive DTH armin increases and atropine decreases the reaction formation. The character of DTH on different models is related mainly to the specific features of migration of T-suppressors from the spleen and their content in peripheral blood.

Animals↗
PubMed1983

Effect of repeated delayed hypersensitivity skin tests on skin-test responses.

To determine whether repeated skin tests can augment a previously weak delayed hypersensitivity response or convert previously nonreacting tests and thus yield false-positive data, the authors carried out retrospective analysis of 426 skin tests on 107 patients who had a mean of 4.3 weekly tests with five recall antigens. They also skin tested 10 healthy volunteers weekly for up to 6 weeks. Reactions (induration measured in millimetres) were recorded and a regression and correlation analysis was carried out. Analysis of variance was used to compare reaction means of volunteers for each recall antigen at each time interval. All volunteers were reactive to two or more antigens. In the volunteer group there was no augmentation of initially reactive antigen responses except for Varidase and only after 5 weeks. Of 16 initially negative responses to some antigens in this same group, only 3 were converted to reactions of more than 5 mm, all responses being to purified protein derivative. No conversion occurred in the hospitalized patients. There was no significant correlation between repeated skin tests and the delayed hypersensitivity response to the antigens except for Candida in the retrospective patient group, up to 160 days from the original skin test. The data indicate that there is no augmentation of the delayed hypersensitivity response or conversion of initial nonreacting skin tests with any of the antigens tested except Candida.

Adult↗
PubMed1958

Delayed hypersensitivity. IV. Systemic reactivity of guinea pigs sensitized to protein antigens.

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 microg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.

Allergens↗
PubMed1972

Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte.

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.

Animals↗
PubMed1985

[Dynamics of staphylococcal infection in guinea pigs with delayed hypersensitivity to Staphylococcus aureus surface antigens].

The relationship between delayed hypersensitivity (DH) to S. aureus surface antigens and the intensity of the infectious process induced by the sublethal infection of guinea pigs with S. aureus was studied. The protective effect, manifested by a decrease in the staphylococcal contamination of the spleen tissue and by an increase in the level of the activation of lymphocytes, was shown to correlate with DH induced by inactivated staphylococcal cells. In infected guinea pigs having DH to different staphylococcal antigens the disease either took a more severe course (in cases of DH to cell wall or peptidoglycan) than in the animals subjected only to infection, or no aggravation of the disease was observed (in cases of DH to protein A).

Animals↗
PubMed1976

Cellular and humorial immune responses in mice. III. Acceleration of delayed hypersensitivity response by presensitization with suboptimal dose of antigen.

Delayed hypersensitivity (DH) response in mice induced by subcutaneous (s.c.) injection of optimal dose of sheep red blood cells (SRBC) 10(8)) was accelerated by s.c. injection of the antigen of 10(3) or more doses, given 2 or more days earlier. The accelerated response appeared soon after the injection of optimal antigen dose, that is, 1 or 2 days earlier than the response of non-presensitized control. The acceleration was antigen specific. The accelerated response was generally accompanied by an acceleration and/or enhancement of humoral antibody response. Parallel to the acceleration of DH response, the proliferation of regional lymph node cells in the presensitized mice was induced immediately after the following injection of 10(8) SRBC, 1 day earlier than that of non-presensitized animals. These results suggest that presensitization of mice with the antigen induces DH-related memory cells which proliferate immediately after the following injection and function as effector cells for DH reactions, and that the development of DH-related memory cells occurs in close relation to that of helper thymus-derived (T) cells for antibody production.

Animals↗
PubMed1983

Delayed hypersensitivity in squamous cell carcinoma of the oral cavity.

Delayed hypersensitivity response to Dinitrochlorobenzine (DNCB), Purified Protein Derivative (PPD) and Candida albicans abstract (Dermatophytin 'O') was observed in 60 patients of squamous cell carcinoma of the oral cavity and 40 normal controls. The response to all these three antigens were significantly impaired in cancer patients as compared to normal controls. PPD and Dermatophytin 'O' response showed progressive decline with increasing tumour burden. Patients with well differentiated tumours responded well to all these three antigens as compared to those with poorly differentiated tumours.

Adult↗
PubMed1976

Effect of rifampin on immunity to tuberculosis and on delayed hypersensitivity to purified protein derivative.

Mice vaccinated with mycobacterial ribonucleic acid (RNA) produced a high immune response and did not develop delayed hypersensitivity to purified protein derivative (PPD), and rifampin had no effect on the immune response. Mice vaccinated with viable H37Ra cells produced a high immune response and did develop delayed hypersensitivity to PPD. Rifampin had no effect on this immune response, but reduced the footpad reactions to PPD. Both mycobacterial RNA and poly(A:U) served as adjuvants for induction of hypersensitivity to PPD. This hypersensitivity was reduced by the administration of rifampin. Rifampin had no effect on the production of mycobacterial growth inhibitory factor, which is produced following vaccination of mice with mycobacterial RNA or viable H37Ra cells. Rifampin had no effect on the nonspecific phase of the granulomatous response, but did inhibit the secondary allergic phase of this response. The action, therefore, of rifampin that inhibits the induction of delayed hypersensitivity but had no effect on the immune responses against tuberculosis leads to a separation of tuberculin hypersensitivity from cellular immunity to tuberculosis.

Animals↗
PubMed1962

Delayed hypersensitivity to hapten-protein conjugates. II. Anti-hapten specificity and the heterogeneity of the delayed response.

The cross-reactions of conjugates carrying structurally related haptens have been studied in guinea pigs with delayed sensitivity to hapten-protein conjugates. The specificity of the delayed reaction has been found to be a function both of the nature and of the position of the substituent on the benzene ring; the cross-reactions shown in the delayed system, however, have been found to be appreciably more extensive than those reported for rabbit antibody systems employing identical haptens. This finding supports the earlier suggestion that the determinant in the delayed system is functionally larger than that required for reaction of antigen with conventional antibody. Desensitization studies with cross-reacting antigens have indicated that the delayed hypersensitivity response is characterized by the production of a heterogeneous population of cells, all more or less closely adapted to the structure of the homologous hapten conjugate.

Animals↗
PubMed1979

Malignant melanoma. Delayed hypersensitivity skin testing.

One hundred eighty-two patients undergoing initial surgical therapy for primary malignant melanoma were evaluated for delayed hypersensitivity using a battery of recall antigens prior to surgery. Fifty-six patients were also sensitized with 2, 4-dinitrochlorobenzene. All tumors were classified by Clark-Mihm levels and the patients were clinically staged. They were followed up for an average period of 55 months. There was no significant difference in the ability of patients with varied Clark-Mihm level lesions to mount a delayed hypersensitivity response to the recall battery or to 2, 4-dinitrochlorobenzene. Thirteen stage I melanoma patients in whom recurrence developed at a distant site exhibited no difference in immune responsiveness when compared to 148 patients in whom recurrence did not develop when both groups were tested with recall antigens. No difference was noted in patients with stage II disease in whom recurrence developed, as measured by reaction to these same antigens. Twelve patients demonstrated anergy to recall antigens, in none of whom has recurrence developed to date. Fifty-six patients who were tested with 2, 4-dinitrochlorobenzene showed no difference in reactivity with tumors classified at any of the Clark-Mihm levels. Anergy demonstrated by delayed hypersensitivity skin testing appears to reflect increasing tumor burden, rather than a preexisting deficiency that can be used to predict patients at high risk for the development of recurrent disease.

Adult↗