Immunomodulators are drugs that influence the immune system, making it stronger, and can also be used to combat autoimmune diseases.

Animal models are not suitable for researching such immunomodulators because the immune system is different from that of humans. This leads to low success rates in drug development or, in the worst case, to negative effects for the test subjects. Therefore, scientists are developing human models that can better represent the reactions of the human immune system to new drugs than animal models can do which have been used so far.

For example, researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) have established tissue models with the capability of the immune response. Both, primary cells from biopsy material for the analysis of patient-specific characteristics as well as immortalized primary cells are used. One example is an immunocompetent skin model used as an infection model.

The scientists were able to demonstrate the suitability of the model by showing that it is clearly protected against infections with the pathogenic fungus Candida albicans, as is it in healthy humans. Responsible for the protection are the dermal fibroblasts in the model, which secrete antimicrobial peptides and chemokines and can thus stop the invasion of the fungus. The immune cells themselves have an important function in triggering the antimicrobial activity of the fibroblasts.

The researchers also investigated toll-like receptor agonists and antagonists for their effect on the infection model. Toll-like receptors (TLR for short) are structures of the so-called innate immune system. They are located on cell membranes and recognize components of bacteria, viruses, fungi, and protozoa¹. In such a case, the activation of the "antigen-specific acquired immunity" is initiated and modulated. Through the TLR, the innate defense system is able to distinguish between "self" and "non-self". TLR activation results in the release of cytokines. However, persistent or excessive production of inflammatory cytokines lays the basis for the development of autoimmune diseases, which is why some modern therapies aim to neutralize inflammatory cytokines and block their receptors².

Source:
https://q-more.chemie.de/q-more-artikel/328/3d-gewebemodelle-mit-immunkompetenz.html
¹ https://edoc.ub.uni-muenchen.de/21024/1/Roetzer_Laurin.pdf
² https://www.esanum.de/blogs/Immunologie-blog/feeds/today/posts/therapeutische-antikoerper-im-kampf-gegen-inflammatorische-zytokine