The Institute of Immunology conducts research on the immunological mechanisms of viral and bacterial animal diseases and prion diseases. Investigations of different pathogens contribute to the improvement and development of new control strategies and provide the basis for assessing the risks emanating from the release of genetically modified organisms. Research includes the biochemical background of virus replication and the molecular mechanisms of interaction between the virus and the host’s immune system. Particularly, the investigations on virus attenuation and on the use of the parapoxvirus as vector with immune stimulating properties provide new aspects for vaccine development. Exemplarily, we use pestiviruses with targeted attenuating mutations introduced into the genome after molecular biological analysis. The resulting mutants have proven to be excellent vaccines without the otherwise typical persistence of these viruses. In this virus model we also investigate how viral RNase and protease influence the innate immune response and contribute to the establishment of a persistent infection. The parapoxvirus is analyzed as vector system which due to a very early and reliable immune response not only stimulates the antigen-specific reaction but also early unspecific immune responses. Taking H1N1, H5N1, and H7N1 influenza viruses as an example, we investigate nucleic acid based vaccine strategies, concentrating on both, the induction of protective immunity by individual viral genes and their combination as well as the topical application of nucleic acids in pathogenetically relevant tissues.
Other projects of the IfI aim at the elucidation of basic aspects of the cellular and humoral immune response after virus infections. Particularly, interactions of the innate and adaptive immune system with influenzaviruses are investigated focussing on pathogenesis and possibilities for intervention in experimental models. For the influenzavirus infection we have been able to show that immunization with a low pathogenic virus can cause antibody and CD4 T cell-induced protection against a heterologous highly pathogenic virus. In basic experiments we study essential parameters of the immune response to these viruses.
Cell biological investigations are carried out to elucidate the signal pathways and mechanisms of antigen processing for MHC-induced presentation of the viral antigens which are relevant for an efficient immune response. To investigate how viruses suppress the specific cellular immune response, we use papillomaviruses and the parapoxvirus. These pathogens are able to intervene specifically into antigen processing by inhibiting the efficient presentation of peptide antigens on the cell surface by MHC I (classical major histocompatibility antigen I). Viral factors inhibit the expression of antigen-bearing MHC I molecules or their transport to the cell surface. This reduction of antigen presentation should lead to an increased susceptibility of the pathogen-infected cell to control by immune cells of the innate immune system. However this is not always the case, which may be due to a modified signal transduction of members of the immune receptor families. More recent investigations have shown that the exact regulation of the immune response by various co-regulatory immune receptors is essential for the function of the immune system. As the composition of these regulatory immune receptors varies strongly between different species, the investigation of these receptor families is highly relevant for understanding the host specificity of infectious diseases. Furthermore, we carry out studies on alternative antigen presentations (MHC I cross presentations) in dendritic cells (DCs) using as example the facultative intracellular bacterium Chlamydia to see whether this is a counterstrategy against pathogenic immune evasion. DCs play an important role in cellular immune response, as the antigens they present are the first signal for recognition of the infection. The insights gained by this research are essential for understanding the anti-chlamydial defense and contribute considerably to the further development of future treatment strategies.
On the immunological and cell biological level we continue to investigate pathological mechanisms of transmissible spongiform encephalopathies and the physiological significance of the cellular prion protein in connection with antiviral immune mechanisms. Physical and chemical methods are used for a better understanding of the inactivation mechanisms for the pathological form of the prion protein and for application in more easily manageable inactivation procedures.