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Three patients with photoallergy to 3,4',5 tribromosalicylanilide (TBS) following the use of a germicidal soap were studies to determine the mechanism of their photoallergy. None of these subjects had undergone previous patch or photopatch testing. Duplicate patches of purified TBS and its photoproducts 4', 5 dibromosalicylanilide (DBS). 4' monobromosalicylanilide (MBS), and salicylanilide were applied to the skin of the back. One set of patches was irradiated using a source of long ultravoilet whereas all ultraviolet radiation was regorously excluded from the second set. In one patient the results were consistent with a plain contact allergy to the photoproducts DBS and MBS. In a second patient irradiation of any of the three brominated salicylanilides resulted in a reaction whereas no reactions were observed in the dark. A free radical mechanism may be responsible for the formation of the complete antigen in this patient. In the third patient both mechanisms appeared to coexist. Reactions to commercial-grade TBS did not differ from those obtained with pure TBS. [ABSTRACT FROM AUTHOR]

Para-toluic acid (1:4 methylbenzoic acid) and ortho-toluic acid were found to be potent allergic sensitizers when applied to human skin. Cross-sensitivity was found between all three isomers, p-toluic, m-toluic, and o-toluic acids. It is suggested that this cross-sensitivity is explicable in terms of carrier protein specificity rather than by the presence of a common chemical sequence in the hapten or by conversion of the cross-reactants to an identical hapten. [ABSTRACT FROM AUTHOR]

Delayed skin hypersensitivity to specific antigen was enhanced when the antigen was given intradermally with Vibrio cholerae neuraminidase in sensitive subjects. No enhancement of skin test response was seen when inactivated enzyme was used. Neuraminidase exhibited no effect on negative skin-test response in non-sensitive recipients and no re!w1ion at the site of this enzyme was observed in any instance, suggesting that the enhancement effect is immunological in nature. [ABSTRACT FROM AUTHOR]

Delayed hypersensitivity reactions appear to be important in the two main muscular human diseases involving autoimmune anomalies. Using the leucocyte migration test (LMT), a significant abnormality was detected in twelve out of fourteen polymyositis (PM) patients, and in forty out of forty-six myasthenics, in the presence of muscle antigens. No abnormal reactions in the presence of monkey thymus in the LMT were observed amongst the PM patients. as opposed to twenty-one abnormal reactions out of forty-two myasthenics. Secretion of migration inhibition factor (MIF) in the presence of muscular antigens is in accordance with what is known about hypersensitivity reactions during the course of polymyositis. In myasthenia gravis (MG), delayed hypersensitivity to muscle antigens was found to be frequent, and this also applies to thymic antigens, which are considered important in this disease. The role of the T lymphocytes in the neuromuscular junction still remains hypothetical. [ABSTRACT FROM AUTHOR]

An in vitro expression of delayed-type hypersensitivity to tuberculin was tested in Mantoux positive and Mantoux negative persons. Their lymphocytes and monocytes were isolated from venous blood and incubated in vaseline chambers with or without tuberculin. In the presence of tuberculin, a substantially lower percentage of monocytes from Mantoux positive persons spread, than monocytes From Mantoux negative persons. This antigen-induced inhibition of monocyte spreading seems to be a reliable measure of tuberculin hypersensitivity, since it occurs only in Mantoux positive persons and correlates well with the intensity of the tuberculin skin reaction. Reproducibility of the test and the speed with which it is performed could constitute a basis for the use of monocyte spreading inhibition in clinical studies of cell-mediated immune reactions. [ABSTRACT FROM AUTHOR]

Delayed skin reactivity to a battery of antigens was assessed for a series of sarcoidosis patients and closely matched controls. It was compared with the proliferative and cytotoxic capacity of corresponding blood lymphocyte preparations after challenge in mixed lymphocyte culture with an allogeneic lymphoma cell line. Skin anergy to all antigens tested was found only within the patient group having definitely active disease. These patients also showed depression of lymphocyte proliferative response in the in vitro test system as compared to matched controls and to patients with apparently inactive disease. Both of these differences were statistically significant. Skin reactivity to tuberculin was significantly depressed for the whole sarcoidosis group (both active and inactive) as compared to the control group and significant impairment of capacity to develop cytotoxicity in vitro was also found in comparison of these same groups. The results obtained confirm the association of impaired delayed skin hypersensitivity in sarcoidosis with diminished lymphocyte reactivity in vitro, especially when the disease is active. The reduced cytotoxic capacity of sarcoid lymphocytes in vitro may reflect a comparable in vivo impairment and partly explain the depressed skin tests and also contribute to the protracted nature of the disease because of failure to eradicate the postulated `sarcoid agent'. [ABSTRACT FROM AUTHOR]

Chickens of four inbred lines were tested for the development of delayed hypersensitivity to mycobacterial antigens. It was found that WA and WB lines failed to develop tuberculin hypersensitivity. On the other hand, IB line was a strong responder, while the response of CB line was intermediate. [ABSTRACT FROM AUTHOR]

Experiments were carried out to test whether a humoral factor capable of restoring immunological competence to neonatally thymectomized animals was released by the isolated perfused rabbit thymus. New Zealand white rabbits thymectomized within 24 hours of birth received twice weekly injections of cell-free thymic perfusate from the second week of life. Their body weights, peripheral blood lymphocyte counts, and delayed hypersensitivity responses to skin test antigens were compared with those of two control groups of thymectomized rabbits, one that received injections of cell-free perfusate that had been run in a perfusion circuit with no thymus, and another that received no injections, and also with those of normal or sham-thymectomized rabbits. The results suggest that a humoral factor was liberated from the thymus during perfusion which restored delayed hypersensitivity responses to thymectomized rabbits, but had no effect on the depressed lymphocyte count resulting from thymectomy. [ABSTRACT FROM AUTHOR]

Presents cases of ataxia telangiectasia which demonstrate the characteristics, clinical features and immunological abnormalities. Assessment of hypersensitivity skin reactions with antigens; Discussion on the absence of an immunoglobulin; Abnormalities on cellular and circulating antibody responses related to susceptibility to sinopulmonary infections.

The ability of disodium cromoglycate to inhibit IgE-mediated cutaneous anaphylaxis in the rat in vivo and release of histamine from peritoneal mast cells in vitro has been studied. Only when drug and antigen were presented to the sensitized cells simultaneously was a dose-dependent inhibition demonstrable. After the drug had been given alone, in the absence of antigen, either in vivo or in vitro it had little or no action when given again at antigen challenge. In vivo, this refractory state was reversible. It is suggested that disodium cromoglycate may act by releasing some factor capable of inhibiting the release of mediators from the mast cell. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes of twenty-three subjects with grass pollen allergy were cultured with grass pollen antigen for 3 days. After harvesting, the culture supernatants were added to fresh autologous lymphocytes which were maintained in culture for 6 days. Cellular uptake of [³H]thymidine was measured during the sixth day of culture, and revealed that the lymphocyte culture supernatants stimulated greater thymidine uptake than expected from the lymphocyte transformation response to corresponding amounts of antigen. The supernatant factor which mediated this effect was termed `lymphocyte mitogenic factor' by analogy with a similar response of lymphocytes in clinical and experimental delayed hypersensitivity. Lymphocyte culture supernatants were also tested for migration- inhibition factor by their ability to inhibit the migration of guinea-pig macrophages. [ABSTRACT FROM AUTHOR]

Recipient guinea-pigs pretreated with Freund's complete adjuvant alone show depressed 4 hr (Arthus) reactions following passive transfer of antiserum to bovine γ-globulin and human serum albumin. Recipient outbred guinea-pigs and inbred rats also show depressed 24 hr delayed reactions following passive transfer of immune peritoneal exudate cells and serum. This indicates that Freund's complete adjuvant depresses certain inflammatory responses. Donor guinea-pigs and inbred rats pretreated with FCA alone and then immunized with BGG in FCA transfer smaller 24 hr reactions to normal recipients than comparable donor animals which have not been pretreated with FCA. This suggests that pretreatment with FCA depresses the central state of delayed hypersensitivity which normally follows immunization with BGG in FCA. These two findings may explain why pretreatment with FCA depresses the 4 and 24 hr skin reactions which otherwise follow immunization with antigen in FCA. [ABSTRACT FROM AUTHOR]

Skin tests of delayed hypersensitivity were performed on thirty-eight patients of leprosy with a bacterial antigen (tuberculin), a hapten (dinitrochlorobenzene) and allogenic lymphocytic transplantation. The results have indicated that leprosy is associated with a generalized depression of delayed allergic response. The depression is of greater severity in patients with lepromatous leprosy and less among tuberculoid patients. The depression of cell mediated immunity in these cases is not absolute but is relative and depends upon the dose and potency of an antigen and the severity of the disease. [ABSTRACT FROM AUTHOR]

Certain foetal calf sera (FCS), upon initial injection, elicit delayed dermal reactions in some but not all guinea-pigs. The FCS that evoke significant dermal responses also initiate in vitro blastogenesis of lymphocytes taken from animals exhibiting the dermal reactions. A correlation exists between the severity of the in vivo reactions and the degree of blastogenesis observed. An explanation for these observations has been suggested, i.e. that some guineapigs possess spontaneously developed delayed hypersensitivity for antigen(s) contained in FCS. [ABSTRACT FROM AUTHOR]

The effect of cytochalasin B (which selectively inhibits the function of cytoplasmic contractile microfilaments) on IgE-mediated hypersensitivity in human skin was studied. Cytochalasin B inhibited the antigen-induced histamine release from human skin slices sensitized passively in vitro with human reaginic serum. The magnitude of inhibition of histamine release was related to the duration of preincubation of sensitized skin slices with cytochatasin B. The effect of cytochalasin B on antigen-induced histamine release from sensitized skin was reversible, indicating that the inhibition of histamine release may be due to the inhibition of contraction of cytoplasmic microfilaments in sensitized target cells by cytochalasin B. [ABSTRACT FROM AUTHOR]

A proportion of the plasma cells in lymph nodes of allergized guinea-pigs and mice were found to possess membrane-bound receptors for antigen when tested for rosette-formation at 4° by the suspension-centrifugation technique. This was shown by staining rosetted cells with pyronin-methyl green. Rosette-forming cells of the guinea-pig were further examined by staining with fluorescein-conjugated antigen (rabbit Fab') and by electron microscopy. By these techniques it was found that many plasma cells which contain antigen-specific intracellular antibodies do not form rosettes, and that cells of the plasmacytic series represented in the rosetted population are limited to plasmablasts and immature plasma cells. The lack of rosette-forming mature plasma cells suggests that a loss of receptors from the cell-membrane occurs as an accompaniment to maturation. [ABSTRACT FROM AUTHOR]

A previous report of increased intensity and prolongation of contact hypersensitivity in animals pre-treated with cyclophosphamide (CY) has been confirmed using other immunosuppressive agents. Melphalan, ICRF 159 and azathioprine caused a similar increase in contact sensitivity reactions, whereas busulphan, procarbazine and chlorambucil were inactive in this respect. The increased contact hypersensitivity was not associated with increased lymph node activity. Pre-treatment with CY, ICRF 159 and melphalan also caused increased intensity and prolonged Jones-Mote type reactions so that they resembled tuberculin- type reactions. This was associated with a marked reduction in γ1 antibody production. It is therefore suggested that Jones-Mote hypersensitivity is a further example of a T-lymphocyte reaction modulated by a B-lymphocyte response. [ABSTRACT FROM AUTHOR]

In order to determine the relationship between the level of circulating reaginic (IgE) antibody and degree of cutaneous hypersensitivity, rats producing different titres of reaginic antibody were assessed for skin test reactivity by means of the active cutaneous anaphylaxis test. Skin reaction diameters of ovalbumin-sensitive rats were similar whether they were producing low or markedly elevated levels of ovalbumin reagins. In rats infected with Nippostrongylus brasiliensis, skin test reactivity to N. brasiliensis antigen was demonstrable before reagin became detectable in the circulation. It increased to maximum shortly after the appearance of circulating reagin, and thereafter showed no significant increase commensurate with the further rise in reagin titre. The results show that in the rat there is no direct quantitative relationship between the size of skin test reactions and the level of specific circulating reaginic antibody. [ABSTRACT FROM AUTHOR]

Anaphylactic hypersensitivity of isolated guinea-pig ileum preparations has been evaluated by investigation of antigen-dose/response relationships, in vitro. The influence of Freund's adjuvants on active sensitization has been investigated. In contrast to the inhibitory influence previously observed in vivo, the degree of hypersensitivity of isolated tissues in vitro was potentiated by the adjuvants. It is thought that high circulating titres of antibody in vivo exerted a protective or neutralizing effect in relation to challenging doses of antigen. Isolated tissues were freed from this influence. Tissues sensitized with the aid of Freund's complete adjuvant (FCA) revealed the influence of other inhibitory mechanisms, due probably to interaction of various antibody types. [ABSTRACT FROM AUTHOR]

A method is described for the detection of human irnmunoglobulins of the four main classes specific for the penicilloyl group. The technique is an adaptation of the red cell linked antigen antiglobulin reaction based on the finding that benzyl penicilloylated rabbit γ-globulin, specific for human erythrocytes, reacted specifically with erythrocytes but did not agglutinate them. In turn this complex reacted specifically with human penicilloyl antibody and it was then possible to titrate each immunoglobulin class by the addition of anti-immunoglobulin sera. The method described here was used to compare titres of penicilloyl specific immunoglobulins of the same class between different sera. The test was found to be less sensitive than the hapten modified bacteriophage reduction test but had the advantage that individual immunoglobulin classes could be compared. In the absence of a reliable method for the diagnosis of penicillin allergy, it is hoped that the technique described will be a useful addition to existing in vivo and in vitro methods of determining the antibody response of the patient to the penicilloyl group. [ABSTRACT FROM AUTHOR]

A study of the passive cutaneous anaphylactic reaction induced by anti-DNP 7Sγ2 antibodies was undertaken in rats to compare this anaphylactic reaction with that induced by rat reagin. This study revealed that disodium cromoglycate was capable of inhibiting the 7Sγ2 induced PCA reaction immediately following antigen challenge but not the slow developing late reaction. Using various doses of disodium cromoglycate on a series of rat reagin PCA reactions and on a series of early 7Sγ2 induced PCA reactions, similarities in dose dependence were demonstrated suggesting that certain pathways might be common to both reactions. Studies using 48/80 treatment after sensitization revealed inhibition of both early and late 7Sγ2 reactions. Concomitant sensitization with rat reagin and 7Sγ2 at various concentrations demonstrated that either antibody was capable of inhibiting the reaction induced by the other antibody, suggesting similar sensitization sites might be involved. In actively sensitized rats with a high reagin titre we were unable to induce a 7Sγ2 or rat reagin PCA reaction whereas a cutaneous reaction of the 'Arthus' type was readily induced. It is concluded that passive sensitization by anti-DNP 7Sγ2 antibodies has certain factors in common with sensitization by rat reagin and that the sensitized mast cell plays a vital role in the elicitation of both early and late 7Sγ2 PCA reactions. [ABSTRACT FROM AUTHOR]

Contact sensitivity was produced in mice by applying an alcoholic solution of picryl chloride or 2-phenyl-4-ethoxymethylene oxazotone (oxazolone) to the abdominal wall. It was assessed by painting the ear with the contact sensitizing agent dissolved in olive oil and measuring the increase in ear thickness 24 hours later. Contact sensitivity to picryl chloride was depressed by pre-treatment with the sulphonic acid derivative of picric acid. Complete depression was obtained when either two large doses or multiple small doses were given and in the former case this complete depression was still present 6 weeks after the last injection of the sulphonic acid. Similar pre-treatment with oxazolone depressed contact sensitivity to oxazolone in some but not all mice. Pre-treatment with the folic acid antagonist amethopterin before and during sensitization almost completely abolished contact sensitivity, while a single larger dose given 48 hours before sensitization only had a small effect. Mice whose immune response to picryl chloride had been depressed by pretreatment with sulphonic acid and methotrexate were used to study restoration of immune competence by normal lymphoid cells. No restoration was observed when unirradiated recipients were used. However, a mixture of lymph node and bone marrow cells and, to a lesser extent thymus and bone marrow cells, restored immune competence to picryl chloride in irradiated recipients. It was concluded that irradiation favoured the restoration of immune competence by normal lymphoid cells and that a mixture of lymph node and possibly thymus cells with bone marrow cells was able to cause restoration. [ABSTRACT FROM AUTHOR]

Delayed-type hypersensitivity and antibody formation to sheep erythrocytes (SRBC) was studied in rats. Two immunologically specific suppressive effects on the primary induction of delayed hypersensitivity were found : one was short-lasting and due to a direct action of intravenous antigen; the other was mediated by anti-SRBC antibody and demonstrable both as a later-occurring and indirect effect of active immunization and as occurring consequent to passive immunization. Either of these two forms of suppression only partially prevented primary induction of delayed hypersensitivity, but used together their effects were synergistic and completely suppressed development of delayed hypersensitivity. The secondary delayed hypersensitivity response was insusceptible to antibody inhibition. The data concerning delayed hypersensitivity to SRBC in the rat were in some ways analogous to previous findings concerning induction of haemolytic plaque- forming cells to SRBC in the same animal The interpretation that delayed hypersensitivity and humoral antibody formation could represent alternative responses of potential antibody-forming cells to immunological induction was considered. [ABSTRACT FROM AUTHOR]

Sera of rabbits immunized with rat or guinea-pig lymph node cell extract were fractionated by column chromatography. In all cases the fractions which contained antibody were able to suppress the inflammatory response of delayed hypersensitivity reactions, whereas fractions devoid of antibody had no activity. Furthermore, rabbit antiserum to guinea-pig serum, or its fraction rich in antibody, were unable to suppress delayed hypersensitivity reactions, indicating that antibodies to the serum proteins present in the cell extract were not responsible for the anti-inflammatory activity of the anti-cell extract serum, in spite of the close association of LNPF activity with plasma protein in the lymph node extract. Haemagglutination inhibition experiments detected in the anti-cell extract antisera a small titre of specific antibody which may be responsible for the inflammatory suppression. [ABSTRACT FROM AUTHOR]

A preliminary experiment showed that the injection of bovine γ-globulin into guinea-pigs with delayed hypersensitivity to bovine γ-globulin reduced the 24-hour skin reactions to bovine γ-globulin and (to a lesser extent) PPD. The peritoneal exudate cells from the desensitized donors had a reduced ability to transfer delayed hypersensitivity to bovine γ-globulin but a normal ability to transfer delayed hypersensitivity to PPD. Likewise, it was possible to diminish the passive transfer of delayed hypersensitivity to bovine γ-globulin by peritoneal exudate cells, by exposure of the ceils to bovine γ-globulin in vitro. The recipients were tested immediately after cell transfer. This in vitro desensitization was specific, in that the transfer of delayed hypersensitivity to PPD was unaffected. Exposure of cells in vitro to hypotonic conditions and antibody to guinea-pig γ-globulin did not prevent the passive transfer of delayed hypersensitivity. [ABSTRACT FROM AUTHOR]

It is known that serum increases the passive transfer of delayed hyper- sensitivity to certain antigens, such as bovine γ-globulin, in the guinea-pig. This synergic effect of serum in the passive transfer of delayed hypersensitivity to bovine γ-globulin was partly, but not completely, produced by serum to haemocyanin when a mixture of bovine γ-globulin and haemocyanin was used for skin testing. It was concluded that part of the synergic action of serum was due to a local inflam- matory reaction. The ability of serum to cause local retention of antigen in the skin was studied using antigens labelled with radioactive iodine. Immune serum favoured the local reten- tion of antigen. The passive transfer of antiserum to bovine γ-globulin, egg albumin and haemocyanin specifically increased the retention of antigen two- to twelve-fold. This ability of serum to cause the local retention of antigen at the site of intra- dermal injection was present in serum taken 3 weeks after immunization with bovine γ-globulin in Freund's complete adjuvant but absent in serum taken at 1 week. Antiserum also altered the distribution of antigen at the skin site. Autoradio- graphy showed that it increased the area over which an appreciable concentration of antigen occurred. Active immunization with bovine γ-globulin had a slight effect on the total amount of antigen retained in the skin after intradermal injection. It had a greater effect on the distribution of antigen. In control guinea-pigs 87 per cent of the total amount of bovine γ-globulin retained at 20 hours was found within a radius of 6·5 mm of the centre of injection. In contrast in guinea-pigs immunized with bovine γ-globulin in Freund's complete adjuvant 43 per cent was found beyond this radius. A similar change in the distribution of human serum albumin was seen in guinea-pigs immunized with bovine γ-globulin when the albumin was mixed with bovine γ-globulin. This indicated that factors other than the formation of immune precipitates were sometimes responsible for the local retention of antigen. The total amount of purified protein derivative of tuberculin (PPD) retained and its distribution in the skin was uninfluenced by immunization. [ABSTRACT FROM AUTHOR]

In outbred guinea-pigs with a low level of hypersensitivity to hen egg albumin (HEA) at a time when circulating antibody was not detectable, unaggregated HEA in extracutaneous tissues was rapidly lost from the injection site and did not elicit lesions of delayed hypersensitivity. Aggregated HEA, however, was retained at the depot site and produced lesions in the bladders of similarly prepared guinea-pigs. In Hartley guinea-pigs with a high level of hypersensitivity, as measured by skin reactions, unaggregated HEA, though rapidly dissipated from depot sites, elicited lesions in the bladder. Aggregated HEA, though retained at injection sites, did not produced reactions of delayed hypersensitivity in kidney, testis and muscle. The inflammation of delayed hypersensitivity did not influence the disappearance rate of labeled HEA from the lesion, while the inflammation of an Arthus response was associated with retention of labeled antigen at the injection site. [ABSTRACT FROM AUTHOR]

Rat thyroglobulin with a high degree of ultracentrifugal purity can be obtained by zone ultracentrifugation of crude thyroid extracts. The thyroglobulin fraction was even more effective than the original extract as an antigen for the production of experimental allergic thyroiditis. Material in the extracts with lower sedimentation coefficients than thyroglobulin were ineffective as antigens in this respect as was a homologous thyroid microsomal fraction. [ABSTRACT FROM AUTHOR]

A method has been described for quantitative measurement of the intensity of cutaneous delayed hypersensitive reactions in rats. This method is based on the measurement of the weight of skin infiltration at the site of cutaneous reaction. In vivo decomplementation of rats with antigen-antibody complexes or aggregated γ-globulin is accompanied by a decrease in delayed hypersensitivity responsiveness. When the level of serum complement is reduced by 90 per cent delayed hypersensitive reactions are completely suppressed. The results presented, although suggestive, do not provide a definite proof of the role of complement in the development of delayed hypersensitive reactions in the skin. [ABSTRACT FROM AUTHOR]

Antibody was obtained in rabbits following immunization with porcine chondromucoprotein and complete adjuvant. Several constituents of the antigen were only revealed by prior hyaluronidase digestion, while an antigenic constituent revealed without hyaluronidase treatment was found to be shared by chondromucoproteins from several other species. Cross-reactivity was confirmed by tanned cell haemagglutination-inhibition and by delayed hypersensitivity reactions in guinea-pigs. Electrophoresis of chondromucoprotein gave some separation of the immunologically distinct constituents. The results suggest that chondromucoprotein may be made up of several species-specific proteins as well as a polysaccharide-peptide of common occurrence in several species. No evidence for antibody directed against chondroitin sulphate was found. The antibody has been used for the localization by immunofluorescence of chondromucoprotein in sections of tissue. [ABSTRACT FROM AUTHOR]

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: 200 R. whole body irradiation in guinea-pigs, while suppressing circulating antibody response, did not prevent the development of delayed hypersensitivity. Irradiated and non-irradiated hypersensitive animals had an equal febrile response to systemic challenge with specific antigen. 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. [ABSTRACT FROM AUTHOR]

Some assumptions underlying the attribution of a high discriminatory capacity to anaphylactic tests have been investigated in model systems, using two tests of the anaphylactic response—the Dale-Schultze reaction and the measurement of histamine released from chopped lung. It has been demonstrated that there may be no response to challenge with a second antigen after desensitization to the first even though the tissues can be shown to be sensitized to the second antigen, i.e. there is a possibility of the occurrence of ‘false’ negative results. The potentiality of response to the second antigen appears to depend partly on the proportion it formed of the sensitizing mixture and partly on the absolute dose used in sensitization. It has been confirmed that desensitization is a graded phenomenon related to dose of antigen and it is shown that it is reversible with time. These factors are likely to complicate the performance and/or interpretation of experiments with tissue extracts and constitute a source of potential false positive results. These factors are of less importance with the histamine-release test than with the Dale-Schultz test. For the Dale-Schultz reaction the ileum proved to be a more satisfactory test tissue than the uterus. In general, there was no significant difference in discriminatory capacity between the histamine-release test and the Dale-Schultz test, but there were more sources of error in the performance of the Dale-Schultz test, while the histamine-release test though more laborious to do gave results which were more amenable to statistical analysis. It is concluded that with careful experimental design the tests could possibly be of use in some investigations of antigen mixtures provided that the sources of false positive results were recognized and due precautions taken. [ABSTRACT FROM AUTHOR]

The sensitivity of two anaphylactic tests, the Dale-Schultz reaction and the measurement of histamine released from chopped lung, have been investigated and compared in model systems. Both tests proved to be highly sensitive in animals sensitized to a single antigen, the Dale-Schultz test being more sensitive on occasion, but less consistent than histamine-release from the lung. In general, the sensitivity to a particular antigen was decreased if more than one antigen was used for sensitization. [ABSTRACT FROM AUTHOR]

The antigenic properties of a group of synthetic poly-iminoacids have been tested in guinea-pigs and rabbits by active cutaneous anaphylaxis, delayed skin hypersensitivity reactions, passive cutaneous anaphylaxis (PCA), tanned cell agglutination and agglutination-inhibition. The antigenicity of a linear homopolymer, poly-L-proline, has been demonstrated in guinea-pigs. This polymer exists in two forms differing only in their secondary structure, Form I having a righthanded helix and Form II a left-handed helix. That both forms are antigenic and yet non-cross-reacting emphasizes the importance of secondary structure in this system. Comparison of polyprolines of different molecular weights suggests the presence of more than one antigenic determinant; a polymer of an average molecular weight of 1500 was antigenically deficient compared with a polyproline of a molecular weight of 17,000. No cross-reactions were detected between anti-polyproline or anti-polyprolineglycine and collagen or its derivatives. The possible structure of the antigenic determinants involved is discussed. [ABSTRACT FROM AUTHOR]

Forty-one patients with acceptable past histories of allergic reactions to benzylpenicillin (PG), eleven patients with questionable histories to PG and thirty patients without past histories of allergic reactions to PG were skin tested with various multivalent haptenic conjugates and with simple chemicals derived from PG in order to determine the antigenic specificities of penicillin hypersensitivity of the wheal-and-flare type. The benzylpenicilloyl (BPO) group was found to be the major haptenic determinant of wheal-and-flare type PG hypersensitivity. Twenty-nine per cent of patients with acceptable histories of PG allergy and 3 per cent of patients without histories of PG allergy gave positive wheal-and-flare reactions to multivalent BPO-conjugates. Three patients who had unusual clinical forms of PG allergic reactions demonstrated patterns of wheal-and-flare reactivity indicating D-penicillamine or D-benzylpenamaldic acid disulphide haptenic specificity. No unequivocal wheal-and-flare reactivity specific for the benzylpenicillenic acid haptenic group was observed in this study. Data were obtained which indicate that BPO-specific wheal-and-flare skin reactivity demonstrates specificity for the entire large BPO haptenic group, and also for structural areas of the immunizing autologous hapten-carrier protein (i.e. carrier specificity). [ABSTRACT FROM AUTHOR]

A technique for elicitation of simultaneous passive cutaneous anaphylaxis and reverse passive Arthus reactions in the same animal is described. Experimental evidence is presented to substantiate previous findings that these two skin reactions, inducible by the same BSA-rabbit anti-BSA system, are distinctive in several species. Dose-response data on Arthus and PCA reactions in the mouse, rat, and guinea-pig indicated that the mouse was least sensitive and guinea-pig most sensitive to these cutaneous reactions. Both types of cutaneous reactions were found to decrease in intensity as well as diameter in response to excess antigen in all three species. [ABSTRACT FROM AUTHOR]

In delayed skin reaction to PPD and BSA in the rat and to old tuberculin and diphtheria toxoid in the guinea-pig, intravenous injection of tritium-labelled thymidine shortly before skin testing produced labeling of a high proportion of the cells entering the perivascular infiltrates 12 - 18 hours later. Administration of thymidine at various times after skin testing gave immediate labelling of 5 - 10 per cent of cells in the infiltrates. It was concluded that the majority of the cells in the infiltrates are haematogenous, that they are synthesizing DNA before entering the lesion, and that many do so in the lesion itself. The principal cell type labelled in both experiments resembled a medium-sized lymphocyte of the lymphoid tissues or large lymphocyte of the blood. There was evidence that over several hours many of these became typical histiocytes. In non-specific reactions, a similar pattern of labelling was observed but the total number of infiltrating cells was very small. [ABSTRACT FROM AUTHOR]

Focuses on the development of delayed skin hypersensitivity towards a purified testis antigen by guinea pigs sensitized by an extract homologous testis and Freund's adjuvant. Maximum reactions in recipients; Transfer of cells from donors.

The fate of lissamine-rhodamine-labelled bovine serum albumin was studied in reversed Arthus reactions and PCA. In reversed Arthus reactions there were accumulations of antigen in the subendothelial spaces and in the endothelial cell layer of vessel walls and the lumina of capillaries and venules as well as extracellularly. After some time granuolcytes took up antigen. In PCA the deposits in vessel walls were not impressive but clearly demonstrable; granulocytes take up antigen within 5 minutes. [ABSTRACT FROM AUTHOR]

The mode of action of disodium cromoglycate has been investigated to determine at what stage in immediate type hypersensitivity reactions the compound is effective. In vitro studies using rat subcutaneous connective tissue sensitized with rat reagin revealed that the compound inhibited the allergic release of histamine if present during antigen challenge. The presence of the compound during sensitization had no effect on antigen-induced release of histamine provided the compound was removed prior to antigen challenge. Tissues which had undergone a primary antigen challenge in the presence of disodium cromoglycate did not release histamine when the compound was removed and the tissues rechallenged. These findings indicated that antigen/antibody interaction occurred in the presence of the compound resulting in desensitization to a subsequent antigen challenge. To corroborate the evidence of the in vitro studies in vivo passive cutaneous anaphylactic reactions (PCA) were undertaken using tissue sites sensitized with two reaginic antibodies which permitted a sequence of antigen challenges. Results from these in vivo reactions demonstrated that it was possible to desensitize tissue, without the release of the mediators of anaphylaxis, by an antigen challenge and disodium cromoglycate treatment. In these sites sensitized with two antibodies the immunological reactivity was maintained following a primary antigen challenge and disodium cromoglycate treatment, as a subsequent challenge with the dissimilar antigen produced a good PCA reaction. It would appear that disodium cromoglycate acts either directly or indirectly at a stage following antigen/antibody reaction but prior to the release of the mediators of anaphylaxis. [ABSTRACT FROM AUTHOR]

The immune response to a protein antigen, keyhole limpet haemocyanin, was studied in fourteen normal subjects and twenty-one patients with solid tumours. Imm- unological responsiveness was assessed by intracutaneous skin testing, by haemagglutinin titres and by in vitro blast transformation. No significant difference was found in the kinetics or magnitude of the immune response among subjects immunized with 0.01, 0.10, or 5.0 mg. Delayed hypersensitivity to keyhole limpet haemocyanin developed in thirty-two of thirty-four skin tested; a positive antibody titre occurred in all; and thirty-one of thirty-five had positive in vitro responses. Patients in good general condition (Group 1) had significantly greater delayed hypersensitivity and antibody responses than the normals but similar in vitro responses. All immunological parameters were depressed in the patients with advanced neoplastic disease (Group 2). Although only skin test positive subjects bad positive in vitro responses, no direct correlation was found between the degree of delayed hypersensitivity and the decree of in vitro blast transformation. Excellent correlation was demonstrated, however, between the in vitro response and the haemagglutinin titre (correlation coefficient +0.52, standard error ±0.09). [ABSTRACT FROM AUTHOR]

Eosinophil leucocytes migrated into the site of PCA reactions mediated by those fractions of 7S guinea-pig lgG containing lgG1; neutrophils were associated with IgG1 and IgG2. Maximal eosinophil infiltration is seen at 12 hr and was associated with degranulation. Intradermal histamine was not eosinophilotactic in guinea-pigs. Performed antigen-antibody complexes of IgG1 and IgG2 both promoted eosinophils and neutrophil migration in guinea-pig skin but slightly more eosinophils were seen following injections of complexes containing IgG1. Local eosinophilia and PCA activity were mediated by a relatively heat-stable element since these effects were demonstrable even after prolonged heating of fractions containing IgG1. Eosinophils were seen following injections of Compound 48/80 and this was accompanied by low mast cell counts; however, there was also some associated tissue destruction. [ABSTRACT FROM AUTHOR]

Extracts of Dermatophagoides farinae cultured on Gaines dog-meal plus yeast, and in particular the `protein' fraction precipitated by ammonium sulphate, give stronger skin test reactions in house dust sensitive patients than extracts of Dermatophagoides pteronyssinus and of house dust. Specific IgE was found against the D. farinae extract in eighteen out of twenty house dust sensitive subjects. Precipitins were found in human sera against extracts of D. farinae, D. pteronyssinus and house dust and also against antigens in cereal and vegetable dusts. These precipitin tests provided evidence of related antigens in extracts of house dust and D. farinae arid in extracts of house dust and D. pteronyssinus, but not in D. farinae and D. pteronyssinus. [ABSTRACT FROM AUTHOR]

The use of human leucocytes for in vitro studies of histamine release is reviewed. Several theoretical aspects and applications of the in vitro procedure are discussed. These include sensitivity of the cells to antigen as a reflection of disease severity, in vitro assays of reagin and the effect of parenteral immunization on the activity of human reaginic and blocking antibodies. [ABSTRACT FROM AUTHOR]