At the biomolecular and cellular levels
Collaboration between various cell types is a characteristic feature of human cellular defence systems. For example, antigen-presenting cells release signal peptides, cytokines, and present foreign antigens to T-lymphocytes, which in turn release other cytokines that activate B-lymphocytes, cytotoxic T-lymphocytes, natural killer cells, and other cells engaged in immunoinflammatory reactions. A number of adhesion molecules and other accessory peptides positioned on the interacting cells help to potentiate and regulate the response. Furthermore, these accessory molecules, together with chemotactic peptides, chemokines or intercrines, direct lymphocytes, monocytes/macrophages, neutrophils, eosinophils and other cells to specific locations, during infections and other inflammatory reactions. Manifestations of these processes include transient or permanent alteration of cell functions (e.g. activation / deactivation of transcription factors, protooncogenes and tumor suppressor genes, which may lead to neoplasia or programmed cell death), acute and chronic recruitment and activation of various cells (e.g. osteoblasts, osteoclasts, chondrocytes and fibroblasts, which may lead to bone- and cartilage destruction and fibrosis), and acute and chronic systemic symptoms (e.g. fever, acute-phase reactions, anaemia, and anorexia and cachexia).
Characterisation of the natural control of these complex biomolecular interactions is a major field of interest in the Institute. This includes characterisation of the molecular structure of signal peptides and their receptors, their biosynthesis and, if released from the cells, their mode of secretion, the coupling of mediator molecules to specific receptors, and the consequences for the intracellular machinery of the target cell(s). Naturally occurring soluble receptors, high-affinity autoantibodies, and other biological response modifiers in humans are being sought, characterised and purified.
We also investigate in vitro pharmacological agents and other therapeutics for interference with processes that govern signal peptide gene activation -> transcription -> translation -> secretion -> receptor interaction -> target cell alterations in a number of human cell systems.
At the clinical level
Diseases of particular interest to us, and where the above biomolecular and cellular features are of central pathogenetic importance: rheumatoid arthritis, juvenile rheumatoid arthritis, insulin-dependent diabetes mellitus, autoimmune thyroid diseases, multiple sclerosis, osteoarthritis, asthma, allergic skin diseases, AIDS, sepsis caused by both gram negative and gram positive bacteria, malaria, leishmaniasis, parodontitis, adult respiratory distress syndrome, disseminated intravascular coagulation, multiorgan failure as complications to trauma, infections and inflammatory conditions, neovascularization (angiogenesis) in inflammation and neoplasia (metastasis), multiple myeloma, T-cell lymphoma, EBV lymphomas, including lymphomas in allografted individuals (PTLD), bone marrow transplantation (graft-versus-host disease), heart-, heart-lung and liver transplantations, mother-fetus relations, preterm labor.
Monitoring host responses to pharmacological agents, particularly to biologicals, is at the heart of the Institutes research efforts; e.g. investigations of immunogenicity / allergenicity of polypeptides and monitoring (auto)antibody development in patients receiving biologicals (interferons, and other cytokines and cytokine modulators such as 'anti-TNF' and 'anti-IL-1' therapies).
For details, see Inflammation overview