The effect of irradiation on the passive transfer of delayed hypersensitivity

Delayed hypersensitivity was passively transferred in guinea-pigs by lymph node and peritoneal exudate cells. This transfer was unaffected by irradiation with 1000 r given in vitro but was reduced by 1500, 2000 and 3000 r.     

Comparative study of delayed hypersensitivity skin reactions and antibodies to human papilloma (HPV)

Purified human papilloma virus (HPV) was prepared from plantar warts, inactivated by formalin, adjusted to 10¹⁰ particles per 0·1 ml and used in intradermal tests (IDT) on 120 patients having warts at that time, or having had warts in the past, together with sixty-three controls. Antibodies were evaluated in the sera from most of the patients by the indirect immunofluorescence (IF) test before and after the skin tests. The results showed a specific delayed-hypersensitivity reaction (DHR) to HPV, especially in patients with `regressing' or `past' warts (76%). DHR was most frequent in patients with a wart of 6 months–2 years duration (77·0–68·8%) and persisted much longer than antibodies, which disappeared with the passage of time. The incidence of antibodies was much higher after IDT in patients with a positive reaction, thus suggesting a booster effect.     

The effect of irradiation on the fever of delayed hypersensitivity

The effect of total body irradiation on the development of delayed hypersensitivity and on the febrile response to specific antigen has been studied in guinea-pigs with the following results:

1. 200 R. whole body irradiation in guinea-pigs, while suppressing circulating antibody response, did not prevent the development of delayed hypersensitivity.

2. Irradiated and non-irradiated hypersensitive animals had an equal febrile response to systemic challenge with specific antigen.

3. Serum from antigen-challenged, irradiated, hypersensitive animals contained a pyrogenic factor of the endogenous serum type capable of producing fever in normal recipients.

These results support the conclusion that production of circulating specific antibody is not essential either for development of delayed hypersensitivity or for the febrile response of the hypersensitive animal to specific antigen.

     

The effect of aging and acute illness on delayed hypersensitivity.

A group of standard antigens (monilia, mosquito, mumps, purified protein derivative [PPD], staphylococcus toxoid, streptokinase-streptodornase [sk-sd] and trichophyton) were applied to 321 normal volunteers, 60 patients admitted to a medical ward, and 41 patients in an intensive care unit (ICU) to evaluate their delayed hypersensitivity skin test response. Eighty-eight per cent of the normal subjects reacted with at least 5 mm. induration to one or more skin tests without any decrease in reactivity occurring with increasing age. In the hospitalized group, only 62 per cent of the ward and 63 per cent of the ICU patients reacted to the same skin tests. All (8/8) anergic ICU patients tested after discharge regained normal reactivity. Acute illness but not increasing age will impair the delayed hypersensitivity skin test response.     

The effect of 6-mercaptopurine on early human placental explants

BACKGROUND: 6-mercaptopurine (6-MP) is an antineoplastic and immunosuppressive drug. Recently, more women have received this drug during pregnancy. Animal studies have shown that 6-MP has deleterious effects on the fetus, while human data include prematurity, intrauterine growth restriction, low birth weight and malformations that occur especially when the drug is administered in the first trimester of pregnancy. OBJECTIVES: To study the effects of 6-MP on cellular functions of human trophoblast explants. METHODS: Human placental explants (5.5-9 weeks gestational age), that were grown on matrigel, were exposed to medium containing 6-MP for 5 days. Medium alone served as control. Extravillous trophoblast (EVT) cell migration assessment was performed by visual observation. Analysis of proliferating events of the trophoblast cells was assessed by immunohistochemical examination. Apoptosis was analyzed by Tunnel procedure and by anti-caspase 3 staining and hormone level by enzyme-linked immunosorbent assay. RESULTS: 6-MP inhibited migration of EVT cells from the villi to the matrigel with a lower proliferation rate and increased apoptosis of cytotrophoblast cells compared to controls. However, no significant effect of 6-MP on hormone levels was observed. CONCLUSIONS: 6-MP inhibited migration and proliferation of trophoblast cells in first-trimester human placental explant culture.     

No effect of delayed cutaneous hypersensitivity testing (Multitest) on blood lymphocyte counts and functions

The effects of delayed cutaneous hypersensitivity (DCH) testing (Multitest, Institute Mérieux) on lymphocyte counts and functions were studied in seven healthy women. All had normal DCH responses and lymphocyte functions. No influence of the DCH testing on subsequent tests for lymphocyte subpopulations and mitogen- and antigen-induced DNA synthesis was observed. The PPD skin test did not boost or otherwise alter the in vitro lymphocyte response to PPD. It may be concluded that Multitest is a simple way of assessing DCH and that this test does not interfere with repeated in vitro tests of lymphocyte capacity.     

Anti-inflammatory effects of methotrexate on reversed passive Arthus reactions in rats

The anti-inflammatory effects of methotrexate (MTX), an anti-rheumatic drug for treating rheumatoid arthritis, on acute inflammation were studied by using Arthus reactions induced in the pleural cavity and dorsal skin of rats. The effects were compared with those of dexamethasone (DEX), a synthetic analog of adrenocortical steroid, and of ketoprofen (KET), a nonsteroidal anti-inflammatory agent. In reversed passive Arthus (RPA) reactions induced in the pleural cavity by an anti-bovine-albumin serum, DEX significantly suppressed both neutrophil accumulation and plasma exudation at the sites of injection of an antibody, whereas MTX and KET had no effect. In the RPA reaction induced in the dorsal skin by an anti-ovalbumin serum, all three drugs inhibited exudation to the same level. However, DEX and MTX suppressed neutrophil accumulation, whereas KET did not. We found that the oral administration of MTX for 3 days significantly inhibited both neutrophil accumulation and exudation in the RPA reaction in the dorsal skin, suggesting that MTX is an effective anti-inflammatory agent. However, the manifestation of these anti-inflammatory effects might be restricted by differences in the inflammation models in rats.     

The effect of zootoxins on the formation of delayed hypersensitivity]

The effect of bee venom (0.05 and 0.5 mg/kg) and the venom of Vipera lebetina (0.05 and 0.5 mg/kg) on the reaction of delayed hypersensitivity was studied in experiments on CBA mice. The character and trend of the effect was determined by the zootoxin species. The venom of Vipera lebetina completely suppressed the cell immune reaction in a dose of 0.5 mg/kg and produced an adjuvant effect in a dose of 0.05 mg/kg. Bee venom (0.5 mg/kg) failed to cause a suppressive effect and in a small dose (0.05 mg/kg) stimulated cellular immunity. The adjuvant properties of the venoms were comparable with the effect of Evans' blue dye.     

Cell-mediated immunity in leprosy and transfer of delayed hypersensitivity reactions

Eighty-nine patients with leprosy, 65 classified as lepromatous and 24 as tuberculoid, were examined in this study. Skin test responses to protein antigens and dinitrochlorobenzene (DNCB) were depressed in lepromatous patients compared to controls. Tuberculoid patients did not exhibit a significant depression to microbial antigens, but they showed a definite depression in the ability to be sensitized with DNCB. The transfer of delayed hypersensitivity reactions to tuberculin, trichophytin, and lepromin (Fernandez and Mitsuda reactions) was accomplished in lepromatous and indeterminate leprosy patients using viable lymphocytes from donors presenting positive reactions to these antigens. The lepromin reaction was also transferred to patients with South American blastomycosis and cutaneous leishmaniasis. The positive reactions of adoptive immunity were confirmed by histologic examination of skin biopsies.     

Cyclophosphamide-mediated enhancement of delayed hypersensitivity reactions in the lung

The appearance of mononuclear cells, mast cells and mucous cells in the airways was studied in Balb/c mice in relation to cell-mediated immunity reflected as delayed hypersensitivity (DH). The animals were pretreated with cyclophosphamide (Cy) to increase cell-mediated immunity and to decrease the influence of antibodies. Mice pretreated with Cy and epicutaneously sensitized with picrylchloride (PiCl) had stronger DH reactions as compared with sensitized mice not pretreated with Cy. The Cy treatment decreased the IgG antibody formation after sensitization. The Cy-pretreated, sensitized and challenged mice had increased numbers of mucus-producing cells and to some extent also mononuclear cells in their lungs compared with sensitized and challenged non-Cy-treated animals. However, the mucous cell numbers were also increased in Cy-treated, but nonsensitized mice in which most of the airway epithelium had differentiated into mucus-containing cells. The present results indicate that local cell-mediated immunity involves the appearance of mononuclear cells and mucus-producing cells in the lung. This inflammatory reaction is enhanced by Cy treatment, although mucous cell differentiation seems to be induced by exposure to Cy alone.     

The effect of angrod on the delayed hypersensitivity response in rats.

Delayed hypersensitivity was induced in rats by means of sheep erythrocytes and bovine serum albumin-lipid conjugate. Administration of heparin to rats sensitized to either antigen resulted in diminution of the delayed hypersensitivity reaction. Administration of ancrod, however, failed to inhibit the delayed cellular reaction to either antigen. Granuloma formation remained unaffected when rats were injected with either heparin or ancrod. The lack of ancrod effect, in contrast to heparin effect, on delayed hypersensitivity is discussed.     

The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease

Crohn's disease patients on long-term 6-mercaptopurine therapy (more than 4 months) were evaluated for activity of peripheral blood natural killer cells. Natural killer-cell cytolytic activity against K-562 tumor-cell targets was examined, as was natural killer-cell suppression of lymphoblastoid B-cell antibody production. In addition, these patients were studied for their ability to generate antitetanus-specific IgG antibody-producing lymphoblastoid B cells followingin vivo booster immunization. Crohn's disease patients on 6-mercaptopurine therapy had significant reductions in peripheral blood natural killer-cell activity against K-562 targets compared to normals, disease controls, and Crohn's disease patients not on 6-mercaptopurine. Natural killer-cell suppression of lymphoblastoid B-cell antibody production was like-wise decreased in 6-mercaptopurine-treated patients compared to normal controls. In contrast, thein vivo generated lymphoblastoid B-cell antibody responses of Crohn's disease patients on 6-mercaptopurine therapy were not decreased compared to normal, while Crohn's disease patients not on 6-mercaptopurine therapy had significantly impaired IgG antitetanus antibody responses. These findings suggest that 6-mercaptopurine therapy in Crohn's disease affects several lymphoid subpopulations, resulting in a decreased natural killer-cell cytotoxic activity against K-562 target cells and a decreased natural killer-cell ability to suppress lymphoblastoid B-cell antibody production, as well as an improved humoral immune response following tetanus toxoid booster immunization.     

The influence of IgE-mediated reactions on the expression of delayed hypersensitivity in the rat.

The effect of IgE-mediated reactions on the expression of delayed hypersensitivity skin reactions was examined in the rat. It was found that the elicitation of an IgE-mediated reaction at the time of skin test could either potentiate or inhibit the development of delayed reactions. At a fixed level of IgE sensitivity, large delayed reactions were potentiated and small delayed reactions suppressed. These interactions were not dependent on the two types of sensitivity being direct against the same antigen but were dependent on the reaction of IgE with its appropriate antigen.     

The effect of ablation of eosinophils on immediate-type hypersensitivity reactions.

The effect of ablation of eosinophils on hypersensitivity reactions in guinea-pigs was tested by administration of rabbit antiserum to the eosinophil (AES) and by administration of glucocorticoids. Both AES and methylprednisolone ablated eosinophils from the blood and peritoneal cavity of test animals. Neither administration of AES nor methylprednisolone, however, altered passive cutaneous or systemic anaphylactic reactions when compared to reactions occurring in control animals treated with normal rabbit serum (NRS). Also there was no consistent effect of AES on the intensity of the Arthus reaction. The effect of ablation of eosinophils on histamine release in the passively sensitized peritoneal cavity of the guinea-pig was also tested. In five experiments a significant reduction in histamine release was seen in AES-treated animals. Ablation of eosinophils by cortisone acetate also resulted in a marked reduction in the quantity of histamine released into the peritoneal cavity following passive sensitization and antigen challenge. Histamine release following intraperitoneal injection of compound 48/80 was not affected by either the prior administration of AES or cortisone acetate, suggesting that the stores of histamine were not depleted by these agents. Overall these results suggest that eosinophils do not play a prominent role in initial expression of immediate-type hypersensitivity reactions where the density of these cells in tissues is low. When present in larger numbers, however, eosinophils may contribute to histamine release in immediate-type reactions.