Immunologische Studien am Omentum V

1970 ◽  
Vol 25 (10) ◽  
pp. 1160-1163 ◽  
Author(s):  
W. F. Krüsmann ◽  
H. Kasemir ◽  
W. Ax ◽  
H. Fischer

Neonatally thymectomized mice show a markedly reduced mesothelial proliferation following an antigenic stimulus. As thymectomy causes a drastic reduction of circulating lymphocytes, lymphopenia may be the cause of the reduced mitotic rate of mesothelial cells. In order to prove this hypothesis, lymphopenia was caused by a) drainage of the thoracic duct and b) by injection of anti-thymocyte serum. In both types of experiments a drastic reduction of mesothelial proliferation was observed showing good correlation with the degree of lymphopenia. These results indicate that lymphocytes of thymic origin release mitosis promoting factors and thereby contribute to an immune response.

2020 ◽  
Vol 4 (4) ◽  
pp. 5-11
Author(s):  
Ioanna Zerva ◽  
Vasileia Pateraki ◽  
Irene Athanassakis

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.


1970 ◽  
Vol 42 (1) ◽  
pp. 90 ◽  
Author(s):  
Arthur E. Bogden ◽  
James R. Eltringham ◽  
Donald R. Anderson

1970 ◽  
Vol 131 (4) ◽  
pp. 675-699 ◽  
Author(s):  
J. F. A. P. Miller ◽  
G. F. Mitchell

Collaboration between thymus-derived lymphocytes, and nonthymus-derived antibody-forming cell precursors occurs during the immune response of mice to sheep erythrocytes (SRBC). The aim of the experiments reported here was to attempt to induce tolerance in each of the two cell populations to determine which cell type dictates the specificity of the response. Adult mice were rendered specifically tolerant to SRBC by treatment with one large dose of SRBC followed by cyclophosphamide. Attempts to restore to normal their anti-SRBC response by injecting lymphoid cells from various sources were unsuccessful. A slight increase in the response was, however, obtained in recipients of thymus or thoracic duct lymphocytes and a more substantial increase in recipients of spleen cells or of a mixture of thymus or thoracic duct cells and normal marrow or spleen cells from thymectomized donors. Thymus cells from tolerant mice were as effective as thymus cells from normal or cyclophosphamide-treated controls in enabling neonatally thymectomized recipients to respond to SRBC and in collaborating with normal marrow cells to allow a response to SRBC in irradiated mice. Tolerance was thus not achieved at the level of thelymphocyte population within the thymus, perhaps because of insufficient penetration of the thymus by the antigens concerned. By contrast, thoracic duct lymphocytes from tolerant mice failed to restore to normal the response of neonatally thymectomized recipients to SRBC. Tolerance is thus a property that can be linked specifically to thymus-derived cells as they exist in the mobile pool of recirculating lymphocytes outside the thymus. Thymus-derived cells are thus considered capable of recognizing and specifically reacting with antigenic determinants. Marrow cells from tolerant mice were as effective as marrow cells from cyclophosphamide-treated or normal controls in collaborating with normal thymus cells to allow a response to SRBC in irradiated recipients. When a mixture of thymus or thoracic duct cells and lymph node cells was given to irradiated mice, the response to SRBC was essentially the same whether the lymph node cells were derived from tolerant donors or from thymectomized irradiated, marrow-protected donors. Attempts to induce tolerance to SRBC in adult thymectomized, irradiated mice 3–4 wk after marrow protection, by treatment with SRBC and cyclophosphamide, were unsuccessful: after injection of thoracic duct cells, a vigorous response to SRBC occurred. The magnitude of the response was the same whether or not thymus cells had been given prior to the tolerization regime. The various experimental designs have thus failed to demonstrate specific tolerance in the nonthymus-derived lymphocyte population. Several alternative possibilities were discussed. Perhaps such a population does not contain cells capable of dictating the specificity of the response. This was considered unlikely. Alternatively, tolerance may have been achieved but soon masked by a rapid, thymus-independent, differentiation of marrow-derived lymphoid stem cells. On the other hand, tolerance may not have occurred simply because the induction of tolerance, like the induction of antibody formation, requires the collaboration of thymus-derived cells. Finally, tolerance in the nonthymus-derived cell population may never be achieved because the SRBC-cyclophosphamide regime specifically eliminates thymus-derived cells leaving the antibody-forming cell precursors intact but unable to react with antigen as there are no thymus-derived cells with which to interact.


1967 ◽  
Vol 125 (4) ◽  
pp. 619-628 ◽  
Author(s):  
Stephen I. Morse ◽  
Sallie K. Riester

The 24 hr volume flow, cell concentration, and total cell output of thoracic duct fluid from mice with pertussis-induced hyperlymphocytosis were markedly reduced when compared with values obtained in normal animals. An increase in the number of circulating lymphocytes occurred in several of the pertussis-treated mice despite the presence of an indwelling thoracic duct cannula. The drainage from such animals also showed a reduced cell concentration and total cell output. It is suggested that lymphocyte recirculation may be minimal in pertussis-induced lymphocytosis, and the evidence obtained also suggests that lymphocytes may enter the blood stream by direct routes during the course of the reaction.


2001 ◽  
Vol 193 (11) ◽  
pp. 1227-1238 ◽  
Author(s):  
Paul D. Rennert ◽  
Paula S. Hochman ◽  
Richard A. Flavell ◽  
David D. Chaplin ◽  
Sundararajan Jayaraman ◽  
...  

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired immunity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs are absolutely required for generating contact hypersensitivity, a T cell–dependent cellular immune response induced by epicutaneous hapten. We show that the homing of epidermal Langerhans cells in response to hapten application is specifically directed to LNs, providing a cellular basis for this unique LN function. In contrast, the spleen cannot mediate contact hypersensitivity because antigen-bearing epidermal Langerhans cells do not access splenic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by reversing the LN defect in lymphotoxin-α−/− mice, thereby restoring the capacity for contact hypersensitivity.


1963 ◽  
Vol 117 (5) ◽  
pp. 799-812 ◽  
Author(s):  
Arthur M. Silverstein ◽  
Jonathan W. Uhr ◽  
Keith L. Kraner ◽  
Robert J. Lukes

The fetal lamb in utero is able to form large amounts of specific antibody in response to antigenic stimulus as early as the 66th to 70th day of the 150 day gestation period. Among the several antigens employed, the fetal lamb responded earliest, and with the highest titers, to bacteriophage φX. Slightly less effective as an antigen was horse ferritin, while ovalbumin proved to be a weak antigen, especially in younger fetuses. Ineffective in stimulating an antibody response at any time during fetal or early neonatal life were diphtheria toxoid, Salmonella typhosa, and BCG. Thus, it may not be feasible to fix precisely the time of onset of immunologic responsiveness in a species, inasmuch as it appears to differ so greatly from one antigen to another. The quantity of antibody found 10 days after φX immunization was not significantly different in fetuses injected at 60 to 120 days of gestation. The earliest anti-phage antibody produced by the lamb fetus is a macroglobulin sensitive to the action of 2-mercaptoethanol. Only in older fetuses with longer lasting stimuli were appreciable amounts of 7S γ-globulin antibodies formed. The conformity of these observations to theories on the ontogenesis of the immune response is discussed.


1966 ◽  
Vol 4 (1) ◽  
pp. 118
Author(s):  
W. S. Tunner ◽  
P. P. Carbone ◽  
W. K. Blaylock ◽  
G. L. Irvin

Author(s):  
О.В. Казаков ◽  
А.Ф. Повещенко ◽  
Н.Б. Орлов ◽  
Т.В. Райтер ◽  
О.В. Повещенко ◽  
...  

Цель исследования - анализ корреляции морфометрии брыжеечных лимфатических узлов и концентрации цитокинов в лимфе грудного протока при химиотерапии рака молочной железы, хирургическом лечении и последующей химиотерапии. Методика. Рак молочной железы индуцировали введением N-метил-N-нитрозомочевины 5 раз с интервалом 7 сут подкожно в область 2-й молочной железы справа. Курс химиотерапии проходил по схеме CMF. Корреляцию между концентрациями 24 цитокинов лимфы и числом клеток структурных зон лимфатических узлов оценивали по коэффициенту ранговой корреляции Спирмена. Результаты. После химиотерапии РМЖ, по сравнению с РМЖ без лечения, морфологические преобразования в лимфатических узлах свидетельствуют о снижении активности местного иммунного ответа. Исследование корреляции концентрации цитокинов в лимфе со структурными изменениями в лимфатических узлах выявило зависимости направленные на повышение иммуномодулирующего и противоопухолевого действия цитокинов. После оперативного лечения РМЖ и последующей химиотерапии, по сравнению только с химиотерапией РМЖ, выявлены положительные связи иммунобластов с цитокином GRO/KC в герминативных центрах, цитокина IL-6 - с митотически делящимися клетками в герминативных центрах и мозговых тяжах, IL-5 - с иммунобластами в мозговых тяжах, хемокина MIP-1a - со зрелыми плазматическими клетками в мозговых синусах. Увеличено количество иммунобластов, средних и малых лимфоцитов в герминативных центрах, возросло количество малых лимфоцитов, незрелых и зрелых плазматических клеток в мозговых синусах. Увеличены площади мозговых тяжей и паракортикальной зоны. Выявлена корреляция: цитокина IL-1α с малыми лимфоцитами, IL-6 с иммунобластами, IL-7 и IL-18 - со средними лимфоцитами, GRO/KC - с иммунобластами, IL-17 - с макрофагами в Т-зависимой зоне; IL-7 и IL-18 - с иммунобластами, IL-12 - с макрофагами, MIP-1a и MCP-1 со зрелыми плазматическими клетками в мозговых синусах. Заключение. После оперативного лечения РМЖ c последующей химиотерапией, по сравнению только с химиотерапией РМЖ, выявлены взаимозависимости концентрации цитокинов в лимфе грудного протока с морфологическими изменениями в брыжеечных лимфатических узлах, которые могут указывать на повышение активности местного звена иммунного ответа. The aim of this study was to analyze correlations of the morphometry of mesenteric lymph nodes with cytokine concentrations in thoracic duct lymph in chemotherapy and surgical treatment with subsequent chemotherapy of breast cancer. Methods. Breast cancer was induced by subcutaneous injection of N-methyl-N-nitrosourea 5 times with 7-day intervals, into the region of the 2nd breast on the right. The course of chemotherapy was performed according to the CMF scheme. Correlations between concentrations of 24 cytokines of the lymph and cells of lymph node structural regions were estimated by the Spearman rank correlation coefficient. Results. After chemotherapy for breast cancer compared to untreated breast cancer, morphological transformations in lymph nodes indicated decreased activity of the local immune response. Analysis of correlations between lymph concentrations of cytokines and structural changes in lymph nodes identified relationships aimed at increasing the immunomodulatory and antitumor effects of cytokines. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, positive correlations were found for immunoblasts with cytokine GRO/KC in germinative centers, for cytokine IL-6 with mitotically dividing cells in germinative centers and medullary cords, for IL-5 with immunoblasts in medullary cords, and for chemokine MIP-1a with mature plasma cells in medullary sinuses. Numbers of immunoblasts and medium and small lymphocytes were increased in germinative centers whereas numbers of small lymphocytes and immature and mature plasma cells were increased in medullary sinuses. Areas of medullary cords and the paracortical zone were increased. Correlations were found for cytokine IL-1α with small lymphocytes, for IL-6 with immunoblasts, for IL-7 and IL-18 with medium lymphocytes, for GRO/KC with immunoblasts, for IL-17 with macrophages in the T-dependent zone, for IL-7 and IL-18 with immunoblasts, for IL-12 with macrophages, and for MIP-1a and MCP-1 with mature plasma cells in medullary sinuses. Conclusion. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, cytokine concentrations in lymph of the thoracic duct were observed to correlate with morphological changes in mesenteric lymph nodes, which may indicate increased activity of the local immune response.


2021 ◽  
pp. 9-14
Author(s):  
R. P. Pavlyuk ◽  
H. A. Myronenko ◽  
U. V. Tymoshenko ◽  
L. N. Lavrovskaya

Summary. The characteristics of variants of antigen D are important because their immunogenicity and, consequently, clinical value depend on them. Objective. To identify weak forms of D antigen of the Rhesus erythrocyte system using available methods, to investigate their frequency and to determine a strategy for interpreting the rhesus status of the individual. Materials and methods. Rhesus affiliation of 3501 blood donors was determined, RhD affiliation of 44 people was specified. The studies were performed in hemagglutination reactions on a plane, test tubes, indirect Coombs’ test, micromethod in gel with MCA anti-D IgM, anti-D IgG, anti-D/DVI IgM/IgG, standard universal reagent antirhesus and standard serum antirhesus. Results and discussion. Dweak was defined 1 % among donors, which is no different from its frequency among Europeans. 40 of the 44 subjects had Dweak and were classified as RhD +, 2 – DVI + — as RhD–, taking into account the world practice of referring an individual with serologically weak D depending on the category of the subject. Conclusions. Due to significant differences in the immune response of individuals with Dweak and Dpartial to D + antigenic stimulus, in-depth examination of their RhD status is appropriate to determine transfusion and obstetric tactics.


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