The Immune System – Multimedia

Kinase inhibitors (KIs) represent a new class of rationally designed drugs. The success of Imatinib has prompted the development of other KIs for the treatment of various cancers and inflammation. Although more successful than conventional therapies, myelotoxicity and cardiotoxicity are often major side effects of KIs. In order to predict if newly developed molecules demonstrated significant myelotoxicity or cardiotoxicity, we assessed a number of TKIs using in vitro models.

Natural Vibrio cholerae infection generates a robust B-cell response that wanes for T-cell independent antigens, suggesting that B-cell responses may be mediated in a T-cell dependent manner. Patients with cholera develop a memory-effector T-cell response to cholera antigens, and B-cell activation occurs after T-cell population expansion, suggesting that T-cells may play an important role in the development and maintenance of memory B-cell responses to T-cell dependent antigens.

Very long chain polyunsaturated fatty acids (VLCPUFAs) are declining in reserves, since they are produced by oily fish. VLCPUFAs are important in human nutrition because they are responsible for the production of inflammatory mediators such as prostaglandins, the regulation of cholesterol synthesis and its transport, and the maintenance of cellular membranes. This research aims to produce VLCPUFAs in edible plants.

Constitutive TNF-alpha expression is characteristic of the malignant ovarian surface epithelium. Adenoviral mutants hold great promise as gene therapy vectors but their efficacy is hindered by an inflammatory cascade orchestrated by TNF-alpha. We found that delivering TNF-alpha shRNA to ovarian cancer cells using oncolytic adenoviruses could reduce the inflammatory cascade generated by adenoviruses and also had direct anti-tumour activity on the cancer cells.

Successful RNAi experiments and large-scale siRNA screens require efficient delivery of highly functional and specific nucleic acids including siRNA oligonucleotides, shRNA vectors, or micro RNAs into an appropriate cell system. Cell types relevant for immunological research, such as primary T cells and several suspension cell lines, are poorly accessible using reagent-based transfection approaches.

The amaxa Nucleofector® Technology is a well established method for effective, non-viral transfection of any nucleic acid substrate into hard-to-transfect cells, especially suspension and primary cells. With the Nucleofector® 96-well Shuttle® system high throughput applications such as siRNA-library screenings have become amenable for the first time in these cell types. This renders target validation and identification possible in cell types highly relevant for biomedical research. Here we dis

In order to identify host genes required for M. tuberculosis infection and persistence, we developed a phenotypic cell-based assay in both murine and human cells and adapted it for high throughput and high content screening purposes. Knock-down efficiencies above 80% were achieved in “hard-to-Transfect” macrophage cells. Validation of the assay performed with control siRNAs will be discussed.

Protein was extracted from 7-year old FFPE samples of B-cell lymphoma and mamma carcinoma, followed by ULS labeling. Samples were used for single or two color assays using a custom-made antibody array. We observed differential expression levels for several captured analytes. In B-cell lymphoma, expected high levels of IgM were detected, while high levels of CA19-9, a putative marker, were found for the breast cancer tissue.

Recently, we have presented a strategy to identify new marker molecules characteristic for Alopecia areata by combining protein microarray technology with the use of large cDNA expression libraries (Lueking et al., 2005). This strategy is now applied to Juvenile idiopathic Arthritis (JIA), Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) in a BMBF-funded project.

In order to infect a target cell, the HIV envelope glycoprotein gp120 has to interact with both the cellular CD4 receptor and a chemokine receptor, CCR5 or CXCR4, the so-called HIV co-receptors. Several flow cytometric/fluorometric assays are developed in our lab and are very helpful in deciphering the mode of action and interaction site of several classes of HIV entry inhibitors, such as the chemokine receptor antagonists.