This thesis contains several investigations into the contribution of complement proteins, especially C1q, in several human diseases. Additionally, human autoantibodies against C1q (anti-C1q) are... Show moreThis thesis contains several investigations into the contribution of complement proteins, especially C1q, in several human diseases. Additionally, human autoantibodies against C1q (anti-C1q) are studied, cloned and characterized in order to further the understanding of their role in autoimmune disease. Show less
In order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course... Show moreIn order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course.Unravelling the fundamental molecular mechanisms influencing the onset and course of diseases such as allergies, rheumatoid arthritis or cancer can be tackled using bioorthogonal antigens – chemically functionalized proteins.To tackle this challenge this thesis uses an inter-disciplinary approach. Combining standard immunological experimental methods with special, highly selective bioorthogonal chemical reactions. These reactions are bioorthogonal because, unlike normal organic chemistry, they are compatible with the physiological environment of a cell. This approach allows for following for example the location of the protein over time within a cell or alterations in the immune response due to disease related changes to the protein without disturbing the processes themself.This is a significant advantage because without changing the method used, new information can be retrieved from the same set of experiments, at any point in time during the process and a plethora of new readout options yielding additional data sets.This promises new insights into the causal relation of time, localisation and factors influencing effective anti-cancer vaccine-design and cancer immunotherapy or new biological drugs to prevent or delay onset and progression of autoimmune diseases. Show less
The term __chimerism__ originates from Greek mythology and refers to the creature Chimaera, whose body was in front a lion, the back a serpent and the midsection a goat. In medicine, the term... Show moreThe term __chimerism__ originates from Greek mythology and refers to the creature Chimaera, whose body was in front a lion, the back a serpent and the midsection a goat. In medicine, the term chimerism refers to an individual, organ or part consisting of tissues of diverse genetic constitution. Pregnancy, blood transfusion and organ transplantation are potential causes of chimerism. In this thesis the occurrence of chimerism is investigated in different organs of healthy women, of women with the autoimmune disease Systemic Lupus Erythematosus (SLE) and of women that received a renal allograft. To demonstrate chimerism, male cells were detected in female organs by using in situ hybridization of the Y chromosome. Chimerism was found in 18% of healthy organs, in about 50% of organs derived from women with SLE and in none of the skin tumors investigated from female renal allograft recipients. In various organ types and both in women with and without sons and women with and without a transfusion history, chimerism was present. In this thesis we describe these results and review data from the ancient and recent literature. With all these data in hand, we speculate about the sources of chimerism and its implications on immunity. Show less
