Study of systemic fever reaction of the delayed type hypersensitivity

The possibility of elaborating a model of fever reaction to a simple protein antigen, ovalbumin, was investigated. Administration of the antigen in adjuvants into the foot-pads or intravenously proved unsatisfactory and did not sensitize the animal to induction of a fever reaction to a challenging dose of antigen. Sensitization by the simultaneous intravenous administration of ovalbumin together with living BCG vaccine yielded positive results. The fever response to ovalbumin is specific, since rabbits sensitized with BCG vaccine only did not respond to the administration of ovalbumin. The degree of fever reactions to tuberculin and ovalbumin in the individual rabbits was more or less proportional. The given model is reproducible and is useful for experimental studies. Further experiments will be necessary, however, for detailed characterization and for analysis of the mechanism (antibody-mediated or delayed type hypersensitivity).     

Effect of thyroid hormones on delayed type hypersensitivity reaction

The effect of long term administration of thyroid hormones and its deprivation on delayed type hypersensitivity (DTH) reaction to 2-4 dinitrochlorobenzene (DNCB) was studied. Animals were either pre-treated with thyroid hormones (T3 or T4) for 15 days and then subjected to DNCB skin test or the animals received thyroid hormones and simultaneously subjected to DNCB skin test. In both the cases DTH reaction was found to be increased significantly. When DNCB skin test was performed in the thyroidectomized animals, DNCB skin reaction was significantly decreased and the reaction was restored to normal following supplementation of thyroid hormones to the thyroidectomized animals. TLC and ALC were increased significantly following hormone treatment and thyroidectomized animals. TLC hand, induced significant depression in the count which was restored by hormone administration to the thyroidectomized animals.     

The mechanism of the delayed type of hypersensitivity

Кролики были ознак омл ены с БЦЖ вакцины, и посл е гиперчувств ительно сть кожи вак цины, и посл е гиперчу вствительно сть кожи дозе 5 μ (itg) очищ ен ного туберкулина (PT), веде нии внутривен но. Систе мные реакци и туберкули на hypersensitive от кроликов до 5 μ г PT состоит из лихор адка, и lymphopenia изменения в число гра нулоцитов (leucocytosis или leucopenia). Эта доза не производит т ем пературы или карт ина кр ови изменения в контро ля. Гиперчув ствительн ость был переведен пас сивно по клеток (200 до 500 млн.) hypersensitive от кроликов. Она прош ла успешно на использо вании клеток селезенки, перитонеального exudate (сол еных течение четырех ч асов или минеральное нефти в течение 48 часов) и белые клетки перифери ческой крови. В пассивн ом передача гиперчувс твительности в клетка х нормальных получате лей, все проявлений сист емных туберкулина Реа кция может быть вызвал, как в активном сенсибил изированная кроликов. Передача плазмы сенсиб илизированная кролик ов. Передача плазмы раз работка системного зад ерживается гиперчувс твительность в получат елями. Он сделал вывод о том, что результаты туб еркулина системные ре акции в первую очередь вызвала реакцию на hypersenstive клеток с туберкулина.     

The mechanism of the delayed type of hypersensitivity

1. (1)
   Простой метод демон страции цитостатиче ские воздействия раз бавленных туберкул ина и ПТ) на лейкоциты от hypersensitive кролики описана. О пределенный артикль Метод состоит в пятн а и мертвых живых кле ток (лейкоциты, мыть в четыре раза и приост ановлено в Tyrode раствор а) с 1% Конго красного и 0,2% после голубого Нила в течение четырех ча сов инкубации в vitro. Нес колько сто эксперим енты проводились и сто эксперименты пр оводились и гиперсс ылок чувствительно сти кроликов испыта ниям.     
   
   

The mechanism of the delayed type of hypersensitivity

Инкубационный пром ытого клетки hypersensitive кроли ков (лейкоциты, селез енки клеток, лимфоцит ов) в разбавленном туб еркулина в vitro приводит к появлению веществ с pyrogenic действий. Эти веще ств не фигурирует в к онтроля эксперимен тов, в которых клетки hypersensitive Были инкубировали без туберкулина или в которых клетки от н ормальных, не hypersensitive крол иков были инкубиров али.     

Biologic activity of extracts of delayed hypersensitivity skin reaction sites

Extracts obtained from skin sites of delayed hypersensitivity reactions show chemotactic activity for monocytes and lymphocytes but not neutrophils. The soluble extractable factors present at these sites have in vivo activity as well; they promote the accumulation of monocytes in peritoneal exudates and cause inflammatory reactions in the skin of nonimmunized animals. The skin inflammatory infiltrates are predominantly mononuclear and are similar to those of delayed hypersensitivity reactions in actively immunized guinea pigs. The extracts which produced these effects had no detectable MIF activity, nor permeability inducing activity in excess of that obtainable from normal skin.These monocyte and lymphocyte chemotactic factors were analyzed by sucrose density ultracentrifugation. By this technique the distribution of monocyte factors corresponded rather closely with that of the monocyte chemotactic factors obtained from an antigen-activated lymphocyte culture. Similar correspondence was obtained for the bulk of the lymphocyte chemotactic activity present in skin extracts and in culture supernatants. This suggests the possibility that the lymphokine-like substances in the skin extracts might in fact represent lymphokines. Further documentation of this point will provide a link between in vitro and in vivo manifestations of delayed hypersensitivity.     

Transfer of delayed hypersensitivity to leishmanin (Montenegro reaction).

It was possible to transfer the cutaneous leishmanin hypersensitivity (Montenegro reaction) to 7 out of 12 recipients. The diameter of the indurations observed ranged from 8 to 25 mm. Histological examination of skin biopsies from the site of three positive Montenegro reactions showed intense mononuclear infiltrate of lymphocytes and histiocytes, and one biopsy showed the feature of tuberculoid granuloma. Four recipients retested with leishmanin after 11, 22, 25, and 32 days, still showed positive reactions.     

Correlation of tumor specific delayed type hypersensitivity reaction and tumor protection to SV40-induced mKSA fibrosarcoma

Summary Mice immunized by excision of a primary, subcutaneously growing SV₄₀-induced mKSA solid tumor which resisted challenge of homologous tumor cells administered at a contralateral site, were found to develop a specific DTH response to SV₄₀ tumor associated transplantation antigens (TATA).In a two-way criss-cross experiment, this DTH response (assessed by direct challenge) was found to be one-way SV₄₀ specific in that chemically induced, non SV₄₀, MCA tumor failed to elicit a DTH response in mice primed by excision of mKSA tumor.These mice also showed a corresponding one-way specific protection against challenge with live homologous mKSA sarcoma cells. In contrast immunization and challenge of MCA-excised mice with either MCA or mKSA tumor cells, exhibited cross-reactivity in both DTH response and protection against either tumor.Unlike this cross-immunity by the direct challenge method, transfer of immune spleen cells from mKSA or MCA excision-primed mice demonstrated a specific DTH response and protection to the original immunizing, homologous but not heterologous tumor. Tumor resistant, DTH-primed mice remained DTH reactive to the primary tumor cells over a period of 4 weeks. Characterization of the splenic T-DTH cells in mice primed by excision of mKSA tumor, indicated a Lyt 1⁺2⁺ phenotype of cells conferring both the DTH response and the immune protection against mKSA sarcoma in a local (Winn) adoptive transfer assay, thus reinforcing the correlation between the DTH response and the antitumor protection.     

Regulation by the H-2 gene complex of delayed type hypersensitivity

Identity at the major histocompatibility complex (MHC) was essential for successful transfer of delayed type hypersensitivity (DTH) in mice. The regions of the MHC involved differed according to the antigen used for sensitization. In the case of fowl gamma globulin (FGG), identity atI-A was necessary, whereas with dinitrofluorobenzene (DNFB), identity at theK, I, orD region was sufficient. These different genetic constraints probably reflect differences in the mechanisms by which antigens are presented to T lymphocytes. Cells from sensitized (CBA×C57BL)F₁ mice transferred DTH to FGG into parental-strain mice, but transfer was more effective in C57BL than in CBA with the same cell dose. This phenomenon is governed by the MHC, since there was better transfer intoH-2 ^b than intoH-2 ^k mice, regardless of their backgrounds. It may reflect the activity of an Ir gene-dependent process. Cells of one genotype (e.g., CBA), sensitized in chimeric mice derived from two MHC-incompatible strains (CBAC57BL), transferred DTH to both strains. These results do not support the notion that the genetic constraint observed in DTH transfer may be a result of the necessity for sensitized T and stimulator cells to match an identical MHC-coded cell interaction molecule. Rather, they favor the hypothesis that T cells recognize antigen, not as a naked determinant, but in close association with products of genes of the MHC.     

Allergic encephalomyelitis: characterization of the determinants for delayed type hypersensitivity

Three non-encephalitogenic peptides derived from the encephalitogenic myelin basic protein of the central nervous system, produce delayed type hypersensitivity responses and elicit delayed skin reaction in guinea pigs sensitized with either peptide, the encephalitogenic tryptophan region (peptide E) or the basic protein. The amino acid sequence of the peptides is N-Acetyl-Ala-Ser-Ala-Gln-Lys-OH, forming the N-terminal region of the basic protein molecule, H-Gly-Ser-Leu-Pro-Gln-Lys-OH and H-Gly-Ala-Glu-Gly-Gln-Lys-OH representing residues number 69–74 and 117–122 of the basic protein respectively.     

Primary antibody and delayed type hypersensitivity response of mice to ovalbumin

The control of the ability to respond to three doses of ovalbumin has been studied in an attempt to find the minimum dose of antigen necessary for activation of primary antibody response and delayed type hypersensitivity response. In seven of the ten mouse strains studied, concordance of the minimum dose needed to elicit the two responses was observed. Discordance is found in the other strains, suggesting that the ability to respond to ovalbumin is independently controlled in several cells. The antibody and delayed type hypersensitivity responses to ovalbumin are controlled by at least two genes, one localized in the major histocompatibility complex.