This research contributes to the following Sustainable Development Goals, among others:

Immunity, Infection and Tolerance

Fighting illnesses by manipulating the immune system

Our immune system protects us against disease, but every now and then, something goes wrong: an enemy invades our bodies or our immune system attacks our own cells and we become ill. Doctors and researchers at the Leiden University Medical Center (LUMC) want to be able to manipulate the immune system such that it can combat pathogens that enter the body without attacking the body’s own cells.

Recognising the enemy

The immune system protects the human body against its enemies. These are generally infiltrators from outside, such as bacteria, viruses and parasites. The immune system also destroys abnormal autologous cells such as tumour cells. It is an enormous challenge for the immune system to distinguish between harmless substances that enter the body and the many thousands of pathogens. It’s an equally big challenge to distinguish between normal and abnormal autologous cells. Immune cells repeatedly face the choice of whether to attack or tolerate cells. The key thing is to strike the right balance.

Tolerant

Unfortunately, in practice things do not always run smoothly. At times the immune system is too tolerant, and invaders succeed in making us ill. This is what happens with serious infectious diseases like malaria and tuberculosis. Researchers at the LUMC are trying to combat these disorders by activating the immune system in advance. They do this by administering a vaccine – a substance with a harmless element of a pathogen that stimulates the immune system to launch an immune response. The immune system also destroys tumour cells, although these cells sometimes manage to escape its attention. Fortunately, in recent years the options of using the immune system as a weapon in the struggle against such diseases have increased. Researchers in Leiden are also working hard to further develop this form of immunotherapy.

On the attack

As well as sometimes being too tolerant, the immune system can also be too aggressive. In the case of diseases such as diabetes and rheumatism, the immune system attacks the body’s own cells. Researchers at the LUMC are developing new forms of therapy for these conditions by investigating the cause of immune system disorders. In some instances the immune system can be activated by relatively harmless foreign substances, such as pollen or house dust mites, that give rise to allergies and asthma. Leiden researchers are looking for ways to make the immune system of these allergy sufferers more tolerant. In a unique study they are trying to learn from parasitic worms and stomach bacteria, which have found a way of tempering the immune system as a means of self-protection. An over-active immune system can also cause auto-immune diseases, where immune cells attack the body’s own cells. This is what happens with such diseases as diabetes and rheumatism.

 

Organ transplantation

The immune system also plays an important role in organ transplantation. It goes without saying that an donor organ is always a foreign body, which means that the immune system will reject it. This is why patients need to take drugs that suppress the immune system. Leiden researchers are studying a new stem cell therapy, which is expected to have fewer side-effects than the drugs currently used.

Learning from one another

The LUMC has a long tradition of research in immunology. The first kidney transplant in the Netherlands took place in Leiden, and in the 1960s the primary immunological signal proteins, the HLAs (human leukocyte antigens), were discovered here. The immune system uses these ‘antenna molecules’, which are found on the surface of all human cells, to trace infections and changes in autologous tissue. Immunological research in Leiden is typically very multidisciplinary since a disorder of the immune system can affect many different parts of the body. Treatment of the autoimmune disease rheumatism, for example, can result in infectious diseases such as tuberculosis. A concerted approach makes it possible to avoid such secondary effects. Researchers also try to learn by looking over one another’s shoulders. For example, while malaria researchers are investigating how the malaria parasite is able to evade the immune system, diabetes researchers are looking at whether that same ploy can be applied in treating diabetes.