Browsing by Subject "Immunzelle"

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Der Einfluss des Osteoblasten- und Tumorzellfibronektins auf die Immunzellen
(2014) Kraft, Sabrina; Nakchbandi, Inaam
The function of the osteoblastic niche for the hematopoesis is an aim of recent research. This work shows, that fibronectin originating from osteoblasts leads to an increase of hematopoetic stem cells and granulocyte monocyte progenitors (GMP). The most abundant fibronectin isoform in OB is EDA. This thesis gives first evidence that there is a relationship between the differentiation of HSPC, GMPs and EDA. These results were associated with a changed expression in two intergrins, α4ß7 and α5ß1. The impaired differentiation of GMPs also leads to a decrease of myeloid and granulocyte progenitor cells. Additionally, myeloid progenitors displayed an increased production of cytokines inhibiting tumor growth. There also was a decrease of myeloid derived suppressor cells (MDSC), which are normally contributers of tumor growth through a t-cell suppression dependent mechanism and the production of tumor proliferating cytokines. The decrease of these cells should be benefical for the inhibition of tumor growth and indeed there was a decrease of tumor growth in two tumor models (murine melanoma and human breast cancer bone metastases). These results are due to the decreased number of MDSCs and the increased production of tumor proliferating cytokines. This effect was t-cell independent. A correlation between OB-FN and the inhibited tumor growth were verified by adoptive transfer experiments with in vitro differentiation of myeloid progenitor cells in presence and absence of EDA and the induction of melanoma. The presence of EDA during the differentiation was able to induce an increase of tumor growth again. This thesis presents for the first time the influence of osteoblast fibronectin in immune cell differentiation and indirectly on tumor growth. The second part of this work suggests, that the deletion of fibronectin in tumor cells, especially of EDA, leads to an inhibted growth of human breast cancer cells in bone and in an increased number of macrophages in the tumor. The analysis of the cytokine production of tumor-associated macrophages showed a tumor inhibiting cytokine profil, which suggest, that the macrophages in the tumor are so called M1-macrophages. M1-macrophages are known to inhibit tumor growth. The depletion of macrophages with clodronate lipsomes in mice, leads indeed to an increase of tumor growth in absence of the tumor cell fibronectin. For the first time it was therefore show an influence of a changed extracellular matrix production on macrophages in tumors.
Influence of frequent regrouping and social status on behavioral, endocrine and immune responses of group housed pregnant sows
(2020) Schalk, Christiane; Stefanski, Volker
In modern animal husbandry, dynamic group-housing of pregnant sows is a common practice. Every regrouping of animals or every change of group composition is associated with the establishment or the adjustment of a new dominance hierarchy, which provokes aggressive behavior, fights and injuries. This process is known to result in social stress by an activation of different stress systems. The subsequent release of neuroendocrine signals like glucocorticoids (e.g. cortisol) has the potential to alter several immune functions and immune cell numbers in the blood which may be directly associated with animals’ health, reproduction, embryonic development and economic losses. The effects of frequent regrouping or mixing on pregnant sows’ behavior, stress hormones and especially the distribution of blood leukocyte subpopulations represent a major research gap in the field of stress assessment of dynamic group-housing conditions in pig production. The aim of the present doctoral thesis was to evaluate whether frequent regrouping acts as a chronic social stressor influencing behavior as well as the endocrine and immune system of group-housed pregnant sows. Special emphasis was put on the question whether frequent changes of the group composition affect blood leukocyte subpopulations. A study with 40 pregnant sows was designed to investigate the influence of frequent changes of group composition on numbers of blood leukocyte subpopulations in combination with analyses of agonistic behavior and the endocrine status. Pregnant multiparous sows were housed in groups of five animals. Sows were either assigned to a repeated social mixing treatment with a mutual exchange of two randomly selected sows of two specific groups (2x2) twice a week over a period of eight weeks, or remained undisturbed in their original group. Blood samples of all sows were collected during pregnancy at five time points before, during, and after the mixing period to evaluate the number of blood leukocyte subpopulations and plasma cortisol concentrations. Blood immune cell numbers were analyzed during all trimesters of gestation and the impact of social status on these modifications was assessed. Behavioral data of pregnant sows of this experiment were used to compare various recommended dominance indices to rank individuals based on different methodical aspects to investigate whether these indices are comparable and equally applicable for determination of dominance relationships. Results of the current study demonstrated that pregnancy-associated alterations in the immune system generally exist in sows. The numbers of T cells, natural killer cells, B cells, cytotoxic T cells, and CD8+ γδ- T cells decreased during the last trimester of pregnancy, while neutrophils and plasma cortisol concentrations increased during pregnancy. Those pregnancy-associated alterations in the immune system were affected especially in middle-ranking sows, which had higher numbers of B cells and monocytes than sows with lower ranking positions. Plasma cortisol concentrations also tended to be higher in middle-ranking sows compared to low-ranking sows indicating that social rank can influence the immune system and endocrine status in sows during pregnancy. These findings showed the necessity to choose the appropriate measurement for calculation of dominance relationships. Repeated social mixing by frequent changes of group composition not only resulted in an increase of aggressive behavior during the entire mixing period, but also in altered immune cell numbers. The immunological profile in blood of mixed sows was characterized by lower numbers of antigen-experienced T helper cells, cytotoxic T cells and natural killer cells. This work demonstrated that frequent changes of group composition affect both cell numbers of the innate and the adaptive part of the immune system, which may weaken immunological memory functioning and reduce the resistance against certain infections in pregnant sows. For most of these immune cells a certain period of instable housing conditions was required to induce a change, but once manifested, these immunological alterations persisted even after the end of the mixing period. Although the findings of the present work on blood immune cell numbers resemble in many aspects a picture of stress-induced immunomodulation previously reported in context with social stress, no clear differences in measured plasma stress hormone concentrations between treatment groups or rank-positions were found. Whether other factors have influenced cortisol concentrations needs to be further evaluated. The overall picture emerging from the current doctoral thesis indicates that frequent changes of group composition and social status have the potential to induce stress-related immunological changes in pregnant sows which might adversely affect sows’ health.