Immunology in a Petri dish

Publiceret Marts 2016

Living organisms are made up of billions of cells, thousands of genes, proteins and small molecules, which makes the individual microenvironments complex and challenging to replicate in vitro. Focusing on a smaller number of components of such complex systems in in vitro systems simplifies the system under study. This has the advantage, that the basic functions of a defined and selective number of components can be investigated as reduced forms of what happens in vivo.

Extrapolations from animal studies directly to humans are problematic, as it is well known that cellular mechanisms are often species specific. Consequently, using human using cells directly in in vitro methods overcome this translation problem. For compound screening and basic biological mechanistic studies, in vitro experiments are optimal experimental set-ups as they allow for high-throughput screening and essentially unlimited repetitive rounds of experiments, which is not feasible using animal models.

The life science industry in general and the pharmaceutical industry in particular, are increasing their focus on refined in vitro systems to improve early drug discovery and increase the understanding of basic disease mechanisms. Concomitantly, basic research in the field of immunology is moving rapidly and our understanding of the complexity in this field has increased significantly in the last decade. This new knowledge has paved the way for using in vitro immune cell-based models as tools in both traditional early drug discovery, vaccine development and novel stem cell therapies. The immune system is a complex network of specialized cells and organs that work together to protect us from getting ill by recognizing and destroying foreign invaders such as viruses, bacteria, parasites and fungi. Once immune cells receive the alarm of "danger", they become activated and begin to produce the necessary signaling molecules that in turn allow the cells to regulate their own growth and behavior, enlist other immune cells, and direct the new recruits to the trouble spot.

As we progressively learn more about the intricate regulation of the immune system, we also become better at inventing sophisticated in vitro model systems to analyze the interaction, function and regulation of human immune cells and utilize the knowledge to create better and safer treatment for immune related disease. The need for reliable predictive models, especially in the field of drugs and vaccines, to improve efficiency of go/no-go decisions early in development is critical and will have a significant effect on the costs and efficiency of developing medical treatments for patients.

However, a good researcher must always be aware of the limitations of the used in vitro system designed and avoid to draw wrong correlations to the in vivo situation. Care must be taken not to end up like the famous joke of the man looking for a lost coin during the night beneath a streetlight (Figure 1).

In the issue of BioZoom no. 1, 2016, scientists from both industry and university have described their specific use of human immunological in vitro models within both drug discovery, vaccine development and stem cell therapy, covering some of the central elements of merging basic immunology into applied in vitro model systems.

Figure 1. In 1942 a version of the joke appeared in the popular syndicated comic strip "Mutt and Jeff". Three of the five panels in the strip are shown below. The gentleman in the top hat is Jeff, and in the final omitted panel the officer joins Jeff in the search beneath the streetlight. Published 1942 June 3, Florence Morning News, Mutt and Jeff Comic Strip, Page 7. Florence, South Carolina, USA.