Immuno-pathological and immunobiological studies were made of the pathogenesis of adjuvant disease in rats. Results obtained were as follows. 1. Polyarthritis was produced at approximately 70% in rats regardless of the strains by a single injection of the comprete Freund's adjuvant. 2. The disease was induced exclusively by the injection through intradermal route. 3. No serum antibodies directed against components of tubercle bacilli were detected. No direct realationship between RA reaction and swelling of the joints was observed. 4. Histopathological findings revealed characteristic granulomatous proliferative inflammation in the joints, lymph nodes, spleen, lung and liver as a main change, associated with hyperplasia of osteoblast in the wall of the joint. 5. Effects of immunosuppression by young adult thymectomy or injection of ALS (anti-lymphcyte serum) on occurrence of the joint disease were investigated. Young adult thymectomy performed 4 weeks or 3 months before injection of the adjuvant reduced the onset of the joint disease, although the thymectomy shortly before the injection resulted in no effects. The joint disease was inhibited by a single intraperitoneal injection of ALS 1 day, 1 week or 2 weeks prior to the adjuvant injection indicated inhibitory effects on development of the disease. Combination of thymectomy and X-ray irradiation 1 day Before the adjuvant injection or repeated injections of ALS within a week from a day befor the adjuvant injection revealed the most effective prevention from the disease.

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It is well known that the active antigen that induces nephrotoxic antibody is located not only in the kidney (the glomerular basement membrane) but also in various other organs (especially in lung and aorta), and that the antigen is extracted in the form of water-so'uble substance using tryptic digestion. In this paper, nephrotixic serum antigen isolated from rat aortic wall was studeid by enzymatic digestion, gel filtration, zone electrophoresis and fluorescent antiboky technique, and the following findings were obtained: 1) The antigenic activity of four ultrasupernatant samples prepared after digestion by four different enzymes was studeid; the order of antigenic activity was as follows: collagenase->tryptic->elastase->pronase-digested ultrasupernatant sample. 2) Through enzymatic digestion, gel filtration and zone electrophoretic studies, it was demonstrated that the composition of this antigen has the character of glycoprotein, same as that of the glomerular basement membrane. 3) Immunoflurescent studies of rat aortic wall revealed that the nephrotoxic serum antigen is mainly lacated, in the form of intercellular substance, in tunica media.

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The purpose of this studies were to test the ventilatory functions and the bronchial response to methacholine in the children with allergic bronchitis and bronchial asthma. I) Prediction equations in healthy children Healthy 76 children between the ages of 5-15 years (38 boys, 38 girls) were tested in the supine position, em;loying the 9L-AIKA BENEDICT respirometer. All determinations were corrected to BTPS. There were slightly better correlations for both sexes with body surface area (BSA) and all prediction formulas were calculated on BSA. The next lung volumes were measured. 1. Vital capacity = VC 2. Inspiratory reserve volume = IRV 3. Inspir atory capacity = IC 4. Expiratory reserve vo'ume = ERV 5. Rorced expiratory one second volume = FEV_1 6. Maximal breathing capacity = MBC II) Bronchial responses to 2.5% methacholine aerosols in the normal children, and in the children with allergic bronchitis and bronchial asthma. In younger children, Peak Flow Meter (PFM) was used. The conclusions as follows. 1) All asthmatics showed a drop in FEV_1 of 20% or greater (12.5% by PFM), and the normals 19% or lesser (10% by PFM) in all cases. 2) Bronchial respose in the allergic bronchitis lay between that in the asthmatics and in the normals. 3) Higher bronchial hypersensitivity in type II than that in type I. 4) FEV_1% and % FEV_1 revealed within normal range even in the symptomatic allergic bronchitis, but in the asymptomatic asthma, there were showedabnormal decrase. This gas been suggested that these was an essential deagnostic difference between allergic bronchitis and asthma. 5) In allergic bronchitis, a group which bronchial response were 20% or greater was more correlated to allergic history and eosinophilia in nasal smear and sputogram than other group which bronchial response were 19% or lesser. 6) It was found that bronchial response in younger children was able to test using PFM.

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Cross antigenicity among pollens was investigated using following three methods: 1) correlation of the end point of intracutaneous skin test results, 2) in vitro neutralization of reaginic antibody and 3) gell diffusion test using anti-rabbit sera immunized with pollen exriact. Eleven species of tree, 5 species of grass and 16 species of weed were subjected to this study. Following results were obtained. 1) More or less cross antigenicity exists among the most of tree pollens. Complete identity with ceder pollen, which is clinically considered to be the most important antigen among trees, are not found in any of tree pollens. 2) Pine pollen and ceder pollen are quite remote in antigenicity. 3) Common antigen exists among grass pollens tested so far, and orchard-grass or timothy pollen is considered a representative of grasses as antigen. 4) Common antigen exists among family of Ambrosia (ragweed, giant ragweed etc.) and among family of Artemisia (mugworth, anual sage etc.). 5) Even though cross-antigenicity exists among ragweed, mugworth and Japanese hop pollens, they are not closely related and should be considered to possess independent antigen clinically since they are important causative antigen. 6) Each pollen appears to possess its own specific antigen, though some of them are closely realted.

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DNCB sensitization was studied on 29 cases of RA patients and 18 cases of control subjects who had paresis in the lower extremities caused by spinal injury and had no history of allergic diseases. They were all sensitized with 1% acetone solutione of 2, 4-dinitrochlorobenzene, and challenged with 0.1% and 0.01% solution to induce delayed type hypersensitivity. Eighty three per cent of RA patients and fifty per cent of controls showed positive delayed hypersensitivity. RA patients also showed remarkable primary irritant reaction to DNCB. Flare-up phenomenon was observed in many cases of RA patients, which accorded with establishment of delayed type sensitization. It was suggested that RA patients might have hypersensitivity to DNCB and accelerated reactivity to produce delayed type antybody.

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It is necessary that a drug, a sort of simple chemicals should combine with carrier substance to have antigenicity for development od drug hypersensitivity. Significance of carrier protein in simple chemicals allergy was studied by the experiment on animals sensitized with picryl chloride and 2, 4-dinitrobezene sulfonate (DNBSO_3). In animals sensitized with simple chemicals, anaphylactic reaction can not be provocated by the simple chemicals alone, while sometimes shock can be provocated by simple administration of drug in the drug hypersensitivity patients. A hypothesis, that drug hypersensitivity patients would have carrier like substance combining with simple chemicals to produce antigenicity, was exmined by some experiments using DNBSO_3. (1) In the experiments with picryl chloride and DNBSO_3, animals could be sensitized and elicit allergic reaction with conjugates of these simple chemicals with autoserum. It was suggested that autoserum could act as carrier protein in simple chemicals allergy. (2) Antigenicity was proved in mixture of serum and DNBSO_3 under the physiological condition by removing free DNBSO_3. (3) Antigenicity of DNBSO_3-serum mixtures did not differ among those with serum of drug hypersensitivity patients, normal subjects, rabbits and guinea pigs as a whole. However, mixture with some drug hypersensitivity patients serum showed a strong eliciting antigenicity. (4) The mixtures which showed strongly positive reaction were fractionated by Scphadex G-200. Albumin faction which showed remarkable yellow color suggesting strong dinitrophenylation showed no so strong antigenicity, while the other less dinitrophenylated fraction appeared to have antigenicity. It was suggested that quantity in which simple chemicals combined with protein might not accord with antigenicity. (5) Specific carrier substance was not proved in the sera of drug hypersensitivity patients in these experiments A possibility that carrier substance might exist in other factor than serum protein should be considered. Thus, it was concluded that the mecanism to induce drug hyperesnsitivity should not be discussed on the same level of the experiments by DNBSO_3 which had remarkable reactivity with protein, but it was suggested that ability of drug hypersensitivity patients to recognize the drug as antigen might be important.

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Serum complement levels of Guinea pigs sensitized with tubercle bacilli were measured before and after desensitization, in order ot figure out the relation between delayed-type hypersensitivity and complement. Reduction of complement level was well associated with that of humoral antibody titer, and it was concluded in the previous report that a close relation was never proved to delayed-type hypersensitivity. The purpose of this paper is to observe the effect of systemic or local decomplementation on delayedtype hypersensitivity, utilizing the delayed skin reation of tuberculin hypersensitive guinea pigs. 1. The effect of systemic decomplementation of delayed-type hypersensitivity. Nonspecific effect of decomplementation itself cannot be excluded on delayed-type hypersensitivity. Therefore, the improvement of the selection of materials and methods was mandatory. Authors managed to maintain low serum complement level as long as possible and to avoid frequent injections. Materials were as follows: 1. BSA-anti-BSA Complex: injected four times every about six hours. 2. Aggregated Human Ganna Globulin: injected three times every nine hours and two times every twelve hours. 3. Cobra Venom: injected once. Tuberculin skin tests were observed 24 hours after the beginning of these treatments, at the same time, the titer of serum complement was measured and reduced more than 50-90%, except in the group decomplemented by BSA-anti-BSA Complex. The results of these experiments showed no differences in tuberculin skin test between decomplemened and control groups. 2. The effect of local decomplementation on delayed-type hypersensitivity. It was easy to ovserve the reduction of serum complement levels in systemic decomplementation. On the other hand, the measurement of complement levels in tissue was impossible. Therefore, local decomplementation is of extreme usefulness in this case. Anticomplementary agents such as Cu-chlorophyllin, Phlorizin, Cobra Venom, were each mixed with water in oil emulsions and injected circularly in the backs of guinea pigs. The purpose of this method is to decomplement the center of the ring gradually and also for the long period. Tuberculin skin test was performed in the center of the ring and PCA was tested in the center of the opposite site in order to measure the degree of decomplementation. It was noticed that tuberculin skin test was not affected by decomplementation. While PCA was relatively inhibited in accordance with the anti-complementary activity of the materials.

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The cells capable of "Passive Transfer" of tuberculin hypersensitivity obtained from tuberculin sensitized guinea pigs were studied in term of relation between complement and cellular antibody. 1. The effect of systemic decomplementation of the recipient to which tuberculin hypersensitivity was passively transferred. Spleen cells were collected from sensitized buinea pigs after challenge of BCG bacilli and were injected to recipients for the purpose of passive transfer of tuberculin hypersensitivity. In this experiment the recipients were divided into decomplemented groups with cobra venom and non-decomplemented groups. It was observed that there were no differences in the grade of tuberculin skin test between the two groups. 2. Relationship between cellular Antibody and Complement. Immune Adhrerence (IA), Cell Bound C1 Activity (Bound C1) and Complement Activity of destroyed cells (CH50, CIA50, C1, C4, C2, C3, ) were observed by using the peritoneal cells capable of passive transfer, obrained from tuberclin hypersensitive guinea pigs. These cells were consisted mainly of monomuclear cells and were collected after injected with liquid paraffin. In addition, mainly polymorphonuclear cells were collected after injected with broth. However, the latter had no ability of passive transfer. Control groups were the cells incapable of passive transfer, obtained from non-sensitized guinea pigs. IA was observed neither on the sensitized cells nor on the non-sensitized cells. Bound C1 showed no difference between the two groups, including cells mainly consisted of mononuclear ones and of polymorphonuclear ones. Complement activity, for example, CH50, CIA50, C1, C4, C2, C3, could not be detected in each group of cells destroyed with a sonic oscillator. These results suggested that cellular antibody was not in relation with complement. Conclusion: Various kinds of experiments were performed in order to clarify the relationship between delayedtype hypersensitivity and complement. In any experiment the evidence could not be obtained that complement played an important role in delayed-type hypersensitivity. In conclusion, the participation of complement could not be proved in delayed-type hypersensitivity.

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