Type Skin Reactions Research Articles

A Report of Diffuse Interstitial Pneumonia Induced by Chrysotherapy in a Patient with Rheumatoid Arthritis

Gold-induced interstitial pneumonia in a fourty-six years old female patient with rheumatoid arthritis was reported.After she had recieved the last injection of gold sodium thiomalate (cumulative dose; 140mg), she complained non-productive cough and excertional dyspnea in addition to ulcerative stomatitis and generalized dermatitis. Diffuse reticular shadow on bilateral middle and lower lung fields was demonstrated by radiological examination. Pulmonary function revealed restrictive change, impaired diffusing capacity, and hypoxemia. Eosinophilia (7%) was detected, but serum IgE was within normal range. Both immediate and delayed type skin reactions against serially diluted gold salt were negative. Lymphocyte blastoid formation against gold salt increased significantly in the patient as compared with that in healthy person. Gold salt was discontinued and then the treatment with prednisolone (PSL; 30mg/day) was started. Improvement in the chest X-ray film and the pulmonary function test occurred eight months after the beginning of PSL.Gold-induced interstitial pneumonia was highly suspected in this patient because of the mode of onset, the coexistence of stomatitis and dermatitis, and the excellent response to steroid therapy.

Studies on antigenicity, phototoxicity and other specific toxicities of hydrocortisone 17-butyrate 21-propionate (HBP) (author's transl)

The present experiments were undertaken to determine the antigenicity and other toxicities of HBP; such as phototoxicity, photosensitivity, ulcerogenicity, adrogenic-myotropic, estrogenic and progestational activities, and mutagenicity. No antibody formation and delayed type skin reaction of HBP were seen in rabbits. Active systemic anaphylaxis was not observed in guinea pigs challenged by HBP. In the phototoxicity and photosensitivity test, 0.1% HBP ointment, 0.1% HBP cream and 10% HBP acetone solution did not show any skin reaction with or without irradiation of ultraviolet light. Repeated subcutaneous administration of HBP irritated the gastric and intestinal mucosa dose dependently in rats as hydrocortisone 17-butyrate and betamethasone 17-valerate (BV). HBP had neither androgenic-myotropic nor estrogenic activity, but antiestrogenic activity was observed. The progestational activity of HBP in immature rabbit pretreated with estrone was less potent than BV. In the mutagenicity test os HBP investigated by the reverse mutation according to the method by Ames, no significant increase in the number of revertants was observed in the presence or absence of S9 mixture.

Skin Manifestations and Serum IgE Levels in Levamisole-Treated Rheumatoid Arthritis Patients

Skin manifestations may occur as adverse effects of immunostimulant therapy with Levamisole. They are generally regarded as drug-induced hypersensitivity reactions. Our observations revealed that, in Levamisole-treated rheumatoid arthritis patients, urticaria was accompanied by an elevation of serum IgE, but other types of skin reactions were not. Moreover, elevation of IgE occurred without any skin reactions in some cases. It is suggested that Levamisole - stimulating T lymphocytes - may also stimulate IgE-mediated atopic responses.

Stimulation of the Antibody Response to Sheep Red Blood Cells in Piglets and Young Pigs by Levamisole

SUMMARY We studied the in vivo effects of levamisole on the immune response of piglets and young pigs to the thymus-dependent antigen SRBC. There was no effect on the primary antibody response when the drug was administered in saline three days before priming or in incomplete Freund’s adjuvant one week before primary challenge with the antigen. However such treatment resulted in a dose-dependent increase of mercapto-ethanol-resistant antibodies formed in the secondary response to SRBC given three to four weeks after priming. Arthus reactions measured in one of the experiments showed a correlation with the antibody titres, and delayed type skin reactions were also increased by levamisole. We suggest that levamisole stimulates the development of memory T cells.

Cell-mediated immunity during syphilis. A review

Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.

ＢＣＧ経口投与によるがん免疫療法の実験的研究

Among a variety of immunotherapeutic agents, BCG has been employed most popularl yagainst human cancer, and numerous therapeutic experiences have been accumulated, althoughgeneral conclusion is difficult to be reached regarding the therapeutic effects of BCG.The author, in cooperation with Dr. T. Tokunaga (N.I.H., Japan), attempted immunotherap ywith oral BCG against mouse and guinea pig tumors.Animals: dd Y, C57B L /6J and SWM/Ms, and Hartley/F and Strain 2 guinea pigs. Tumors: Ehrlich ascites tumor of dd Y, melanoma B 16 of C57 B L /6 J, fibrosarcoma H9A of Hartley/F, liposarcoma H10 of Hartley/F and Line-10 hepatocarcinoma of Strain 2. BCG (lyophilized;Japan BCG Lab) was administered once or twice a week at 80mg/guinea pig and 5mg/mouse, usually.1) Delayed type skin reaction or footpad reaction were measured with PPD at intervalsafter oral BCG. As controls, animals given single subcutaneous injection with BCG were tested.PPD reactions in animals given oral BCG were much weaker than parenteral BCG. 2) After oral BCG, viable BCG were isolated from Peyer's patch and mesenteric nodes in oral group. Onthe other hand, BCG were isolated from spleen and liver but not mesenteric nodes and Peyer'spatch in parenteral BCG group. 3) Some of Ehrlich tumors regressed spontaneousely when 10cells were inoculated intradermally (18.8%).The tumors in mice given oral BCG regressed athigher rate (54.5%). 4) No effect of oral BCG was shown against melanoma B 16, and hepatoma Line-10. 5) Some of liposarcoma H10 were not taken by Hartley/F, when inoculatedintradermally. However the rate of taking was much lower in guinea pigs given oral BCG.Mean survival length of the BCG group was longer than non-treated control. 6) Thirty threepercent of H9A tumor regressed in guinea pigs given oral BCG, while all grew progressivelyin non-treated control.As shown in reults, some therapeutic effects of oral BCG were indicated in some tumors, such as Ehrlich and H9A, but not in others, such as B16 and Line-10. Dissemination of viable BCG was limitted within Peyer's patch and mesenteric nodes. Obviously oral route is muchsafer than dermal route in terms of BCG infection. Pathologic exa mination of Peyer's patchafter oral BCG revealed that proliferation of both T and B cells and infiltration of macrophagesare remarkable in these areas. We may expect that oral BCG can augment some immunologic Mean survival length of the BCG group was longer than non-treated control.( 6) Thirty threepercent of H9A tumor regressed in guinea pigs given oral BCG, while all grew progressivelyin non-treated control.As shown in results, some therapeutic effects of oral BCG were indicated in some tumors, such as Ehrlich and H9A, but not in others, such as B 16 and Line-10. Dissemination of viable BCG was limitted within Peyer's patch and mesenteric nodes. Obviously oral route is muchsafer than dermal route in terms of BCG infection. Pathologic examination of Peyer's patchafter oral BCG revealed that proliferation of both T and B cells and infiltration of macrophagesare remarkable in these areas. We may expect that oral BCG can augment some immunologic tumor growths.

Characterization of the Allergenic Components of the House Dust Mite, <i>Dermatophagoides farinae</i>

Characterization and purification of the allergenic components of the house dust mite, Dermatophagoides farinae, were investigated. It was found that the mite antigen was heat-stable, pronase-sensitive, and periodate-resistant, which suggested that the antigenic determinants of the mite antigen resided mainly in the protein component. Purification of the mite antigen was tried using Sephadex G-150, DEAE cellulose, and isoelectrofocusing columns. The most potent allergenic fraction was around 20,000-30,000 in molecular weight, although the allergenic activity spread in a wide molecular weight range. Prausnitz-Küstner type skin reactions were performed on rats using mouse homocytotropic antibodies for allergenic evaluation, and the clinical usefulness of this method is discussed.

Experimental Glomerulonephritis in the Rat Induced by Antibodies Directed against Tubular Antigens

In this paper, cell-mediated immunity (CMI) as evaluated by in vitro migration inhibition assays an in vivo delayed type skin reactions in experimental immune complex glomerulonephritis (ECGN) was studied as well as the effect of treatment with immunosuppressive drugs on these immune responses. In glomerulonephritic rats MIF production as well as delayed type skin reactions could be demonstrated directed against tubular brushborder antigen (Fx1A) containing immune complexes or to their constituents (FX1A or rabbit IgG). Treatment of the animals with immunosuppressive drugs during settled disease state (autologous phase) abolished these cellular immune reactions. However, neither the glomerular depositions of rat IgG associated with the autologous phase, nor the urinary excretion was influenced. When treatment of the animals was started simultaneously with the induction of the ECGN both cellular and humoral immune responses as well as proteinuria were affected. It was concluded that although in this glomerulonephritis model specific MIF response after specific stimulation in vitro as well as DTH reactions could be detected against immune complexes or their constituents, these immune reactions seem not to play important role in this ECGN in particular with respect to the proteinuria.

The value of an assessment of erythema and increase in thickness of the skin reaction for a full appreciation of the nature of delayed hypersensitivity in the guinea pig.

Delayed type skin reactions in guinea pigs have been assessed by measuring three parameters: increase in skin thickness, diameter of erythema and intensity of erythema. Some groups of animals were immunized with different protein antigens in Freund's complete adjuvant with or without cyclophosphamide (CY) pretreatment; others received a single high dose of antigen intravenously at the time of immunization. The results emphasize the importance of measuring all three parameters for several days after skin testing. The intensity or erythema was found to be an especially useful parameter for assessing CY-induced modification of delayed hypersensitivity (DH) reactions. The increase in skin thickness, which can be measured objectively, was also valuable as both immediate and DH reactions are characterized by induration. The diameter of erythema could only be measured accurately for a short time after skin testing. Furthermore, the effects of intravenous antigen and CY pretreatment were not reflected by that parameter.

CLINICAL SIGNIFICANCE OF THE HOUSE DUST MITE (DERMATOPHAG01DES PTERONYSSINUS) IN ASTHMATIC CHILDREN IN JAPAN

Clinical studies were conducted to evaluate the role of the house dust mite. Dermatophagoides pteronyssinus, as an allergen in children's asthma in Japan. Skin testing and Prausnitz-Küstner type skin testing showed good correlations between the allergenicity of house dust and the mite. A positive Prausnitz-Küstner type skin reaction to house dust was neutralized by a mite extract. Radioallergosorbent test showed good correlation between house dust and the mite (r=0.687). The mite exhibited in vitro inhibition of radioallergosorbent test to house dust. The inhalation provocation test resulted in an acute respiratory attack in one of the patients. These results suggest that the house dust mite is an important allergen in asthmatic children in Japan.

Prevention of tuberculous cavity formation by desensitization with tuberculin-active peptide.

Repeated injections of tuberculin-active peptide without toxicity prevented cavity formation in rabbit lungs that had been injected with heat-killed tubercle bacilli. This desensitization procedure also suppressed the delayed type skin reaction and the in vitro migration inhibition of alveolar cells with tuberculins, but it had no significant influence upon the passive hemagglutination titer of antipolysaccharide antibody. The correlation between cavity formation and delayed hypersensitivity is discussed.

Photo-inactivated allergens. II. Clinical experience with house dust allergen in pulmonary function tests and in immunotherapy.

SummaryPurified house dust allergen irradiated with UV‐light loses its capacity to elicit immediate type skin and bronchial provocation reactions in the majority of asthmatic patients. However, in some patients both immediate and/or late bronchial reactions were observed to the active house dust and its inactivated counterpart.Immunotherapy with UV‐irradiated house dust allergen, which hyposensitized 66% of forty‐eight asthmatic patients allergic to house dust, was as effective as treatment with aluminium oxide‐adsorbed active house dust, and there were fewer adverse side‐effects.

The differential suppression of antigen, lymphokine and mitogen-induced delayed hypersensitivity-type skin reactions by carrageenan.

Intraperitoneal administration of carrageenan to guinea pigs produced differential suppression of delayed hypersensitivity (DH)-type skin reactions. The order of suppression was antigen-induced > skin reactive factor > concanavalin A. The relationship of the known <i>in vitro</i> cytotoxic effect of carrageenan for macrophages to these findings is discussed. It was concluded that carrageenan probably did not suppress DH lesions by exclusive <i>in vivo</i> macrophage cytotoxicity. It appeared that carrageenan affected both the afferent and efferent limbs of the DH response and that the afferent limb was particularly sensitive. The possibility that the suppressive effects of carrageenan may be mediated by plasma factors is discussed.

Migration inhibition experiments with mixtures of human peripheral blood lymphocytes and guinea pig peritoneal exudate cells.

AbstractMigration inhibition using mixtures of human peripheral blood lymphocytes and non‐sensitized guinea pig peritoneal exudate cells was demonstrable with purified protein derivative of tuberculin (PPD) and Candida albicans extract (CAE) when lymphocytes were obtained from individuals with a delayed type skin reaction to these antigens. No migration inhibition occurred when lymphocytes were used from skin test negative individuals.Furthermore it was found that lymphocytes from some skin test negative persons, which did not induce migration inhibition, showed, however, an increased DNA synthesis when cultured in vitro with PPD. This indicates that a dissociation between the results of migration inhibition, skin test and lymphocyte transformation can occur not only in patients with immune disorders, as has been described by other investigators, but also in healthy individuals.

Effect of Prednisone Treatment on the Human Immune Response to Keyhole Limpet Hemocyanin

The immune responses to KLH injections were investigated in 12 children with asthma, 6 of whom received prednisone for control of asthma. Two injections of 320 <i>μ</i>gN KLH were given 14 days apart. Antibodies were investigated by hemagglutination titration, radioactive antigen-binding techniques and skin testing. The results suggested that therapeutic doses of prednisone, given on alternate days, may have enhanced the primary <i>γ</i>G- and <i>γ</i>M-antibody responses, but had no effect on antibody levels formed after the booster dose of KLH. However, positive wheal and flare skin reactions were somewhat more frequent in the non-steroid treated subjects 4 weeks after the second immunizing KLH dose than in the steroid-treated children. No unequivocal delayed type skin reactions were found in either group.

A comparative study of Mycobacterium gastri and Mycobacterium kansasii by delayed type skin reactions in guinea pigs.

An immunologic method based on the specificity of delayed type skin reactions in guinea pigs has been used for comparing nine strains of Mycobacterium gastri and 17 strains of M. kansasii. The nine strains labeled M. gastri formed a homogeneous group that was distinct from M. kansasii. Within the latter species, the five strains belonging to the weakly catalase-active variety were slightly different from seven strains belonging to the strongly catalase-active variety and five strains of the album variety. The strongly catalase-active strains and the album strains of M. kansasii could not be distinguished by the immunologic method.

Biochemical and Immunological Studies onAspergillus

Two kinds of polysaccharides, glucan and glycopeptide (galactomannan-peptide), were obtained from Aspergillus fumigatus (IFO 5840) by extraction with 50% pyridine and were purified by fractional precipitation with acetone, by a column chromatography on Dowex-50 and DEAE-cellulose and by the gel filtration on Sephadex G-50 and G-200. The glycopeptide, designated APSK-66 fraction, showed both an Arthus and delayed type (tuberculin type) skin reactions in sensitized rabbits and guinea pigs. By treatment with proteolytic enzymes, the delayed type skin reactivity of APSK-66 fraction was reduced but the Arthus type skin reactivity was not affected. However, the Arthus type skin reactivity of APSK-66 fraction was completely lost by periodate oxidation, and the delayed type skin reactivity of APSK-66 fraction was retained. The APSK-66 fraction showed precipitation, complement fixation and passive hemagglutination reactions with rabbit antisera against A. fumigatus. Glucan, designated as APSK-33 fraction, did not show any immunological activity when tested in the present experiment. The chemical structures of the glucan and galactomannan were discussed.

Human Immunologic Response to Soluble Antigens

Abstract Volunteers were injected intradermally and subcutaneously with soluble dinitrophenyl-human serum albumin (DNP-HSA) conjugates. Some responded with increasing titers of mercaptoethanol-sensitive agglutinating antibody to DNP-coupled red cells and some developed immediate type wheal and flare skin reactivity. Serum from one of these subjects was capable of passive transfer of DNP-specific wheal and flare reactions. Thirty-eight of the 55 subjects developed delayed type skin reactions to DNP-HSA. These tended to be maximal in intensity at 24 hr after testing and declined or disappeared by 48 hr in contrast to classic delayed type reactions such as those to tuberculin which are usually prominent at 48 hr. There were also differences in both gross and histologic appearance between DNP-HSA and tuberculin reactions. The response of peripheral leukocytes to antigen in vitro measured by increased DNA synthesis was considerably less to DNP-HSA than it was to tuberculin in individuals who displayed skin reactivity to both. Passive transfer of delayed reactivity to DNP-HSA with dialysates of peripheral leukocytes from sensitive individuals could not be accomplished. In contrast to the characteristic persistence of delayed sensitivity to tuberculin or other microbial antigens, delayed hypersensitivity to DNP-HSA developed early in the course of sensitization and then declined markedly in intensity or disappeared entirely with time and repeated testing. We suggest that this is a general characteristic of the human immune response to the administration of soluble antigens. This may be a distinct form of immunologic response that can be separated from both the serum antibody response and the classic delayed hypersensitivity that is induced by microbial infections or by administration of antigens in complete Freund's adjuvant.

THE IMMUNOGENICITY OF DINITROPHENYL AMINO ACIDS

Numerous dinitrophenyl amino acid preparations injected intradermally induced contact hypersensitivity to dinitrochlorobenzene, delayed type skin reactions to DNP-amino acids, and anti-DNP antibodies in guinea pigs. Some DNP-amino adds induced precipitating anti-DNP antibodies in rabbits as well. Some of the DNP-ammo acids studied were regularly immunogenic, possible immunogenic impurities having been excluded by extensive purification procedures. Others were either constantly nonimmunogenic or irregularly immunogenic, e.g., their immunogenicity varying from one preparation lot to another. By means of extensive chemical analyses and the establishment of dose-response curves, we were able to demonstrate in most cases that the immunogenicity was not due to contamination with unreacted dinitrofluorobenzene or other DNP derivatives, to photodecomposition or other degradation products, or to DNP-protein contaminants. Nevertheless, the irregular immunogenicity of several DNP-amino acid preparations can only be explained by a highly immunogenic impurity (or impurities) which we were unable to detect analytically. The regular immunogenicity of some other DNP-amino acids (e.g. di-DNP-L-histidine) appears to be based on a "transconjugation" phenomenon, the DNP group being able to split off from its amino acid carrier and to conjugate secondarily with proteins in vivo and in vitro. Accordingly, the interpretation of some recent data concerning the immunogenicity of low molecular weight hapten-amino acids may have to be reevaluated.

Immunoelectron microscopic studies on local vascular changes after immunological tissue injuries--especially on the mechanism of nephrotoxic nephritis.

Immunoelectron microscopic study on the interaction between the immune complexes and the local vascular components in nephrotoxic nephritis and ARTHUS type skin reaction was carried out. Conventional histologic and fluorescent antibody observations were also made for reference.The mechanism of the beginning and progression of nephrotoxic nephritis was as follows: The initial binding of heterologous anti‐kidney antibodies to the intrarenal antigenic determinants, which were supposed to be concentrated mainly along the laminae densae of the glomerular basement membranes and partially in the mesangial matrices, and followed by gradually increased incorporation of complement β1c‐components. The hitherto formed immune complexes then appeared in the lamina rarae int. of the basement membranes and in the mesangial areas by non‐immunological transportation and deposition. The successive interactions between the immune complexes and the mesangial cells were assumed to be the essential factor to generate varied features of morphological alterations in the mesangial areas and in other glomerular components.Although this mechanism at the mesangial level had much similarity with the interaction between the deposited immune complexes and the pericytes of the target blood vessels in vasculitis of the AKTHUS type, the causative factor of continuated inflammatory reactions in the glomeruli of the nephrotoxic nephritis were discussed from both immunological and morphological points. ACTA PATH. JAP. 19: 265˜281, 1969.