Dendritic Cells (DC) are the major Antigen Presenting Cells (APC) of the immune system that are involved in initiation of CD4+ and CD8+ T cell responses, as DC display many receptors involved in... Show moreDendritic Cells (DC) are the major Antigen Presenting Cells (APC) of the immune system that are involved in initiation of CD4+ and CD8+ T cell responses, as DC display many receptors involved in antigen uptake, including several types of FcgammaR. However, other APC, like B cells and macrophages also express FcgammaR and MHC class II molecules. In this thesis we show the contribution of these three different APC, in mice, in the Ag-specific MHC class II restricted activation of CD4+ T cells by systemically administrated Immune Complexes (IC). Furthermore, we analyzed the contribution of FcgammaR and the complement system in the presentation of immune-complexed Ag to CD8+ T cells after intravenous administration of IC. Here C1q appeared to play an important role. Next we aimed at identifying the role and importance of individual Fcgamma-receptors in the initiation and regulation of CD8+ T cell responses after subcutaneous injection of IC. Following this route of application, Fcgamma-receptors appeared to be redundant in the uptake and presentation of immune-complexed Ag. Finally, as mice deficient for C5 are unsusceptible to serum induced arthritis and anti-C5 monoclonal antibody treatment prevents arthritis in mice, the question is addressed whether human RA is also associated with C5. Show less
From the earliest times of their evolution, multi-cellular organisms have been defending themselves against infectious agents like nucleic acids, viruses, bacteria, fungi and parasites. Continuous... Show moreFrom the earliest times of their evolution, multi-cellular organisms have been defending themselves against infectious agents like nucleic acids, viruses, bacteria, fungi and parasites. Continuous selection pressure resulted in the development of sophisticated immune systems, which in their adaptive forms have exquisite specificity as well as memory for pathogen antigens. On the other hand, infectious agents developed elaborate strategies to escape from, or counteract, host defense mechanisms. Viruses are totally dependent upon host cells for replication and have developed an impressive variety of mechanisms to shield themselves from being detected by the host immune system. The subject of this thesis concerns a particular example of how viruses, specifically some members of genus Varicellovirus, counteract an important step in one of the acquired immunity pathways: the presentation of antigen by Major Histocompatibility Complex (MHC) class I molecules to cytotoxic T-cells. This thesis describes the discovery of a new family of proteins that inhibit the Transporter associated with Antigen Processing (TAP), and sets the first steps towards the explanation of how these inhibitors interfere with antigen transport by the MHC class I loading complex. Show less
