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Immunological Memory

Measles, rubella, chickenpox – some diseases occur only once in a lifetime. However, thanks to modern medicine, we do not even have to suffer through most of these diseases; a small needle stick with a vaccine is enough to ensure that we are protected against the disease. But how does this protection, which we call immunological memory, work? And what does this memory have to do with arthritis and other chronic inflammatory diseases?

What types of memory cells do we know of?

Immunological memory cells are formed during an immune response and remain in the body even after the disease has subsided. Memory plasma cells continuously secrete specific antibodies that neutralize pathogens and toxins. Memory B cells and memory T cells, which form the so-called reactive memory, are re-activated upon secondary contact with the pathogen and fight the pathogen quickly and highly efficiently. The latest findings suggest that even cells of the innate immune system, i.e. myeloid cells and granulocytes, have a memory.

Pathogenic memory cells are the cause for the chronic course of rheumatic inflammatory diseases.

The body’s own structures are normally ignored by the cells of the immune system. However, this tolerance to “self” can break, which leads to serious diseases such as rheumatoid arthritis, systemic lupus erythematodes, Crohn’s disease or multiple sclerosis. All these diseases have important similarities: they are chronic inflammatory diseases, and they have no cure. We now know the reason for this is because of pathogenic immunological memory. Like protective memory cells, the disease-causing cells are formed during the immune reaction against the body’s own structure. However, since the trigger for the inflammation is not eliminated, these memory cells are repeatedly activated and drive the inflammation to become chronic. Affected people have to take drugs for a lifetime that inhibit these cells but which also have undesirable side effects. Moreover, these drugs suppress the protective immune system.

Can we cure rheumatic inflammation?

The only way to cure inflammatory rheumatic diseases is to switch off the entire immune system and rebuild it from stem cells. However, this procedure, which we call Immunereset, is associated with extremely high risks, since the treated person no longer has any defence mechanisms against pathogens for a certain period of time. Therefore, researchers at the DRFZ are looking for ways to specifically remove only the pathogenic memory cells in order to permanently cure inflammatory diseases.
A prerequisite for this ambitious goal is to know the biology of the various memory cells as precisely as possible.

What do we already know about the different memory cells?

In recent years, we at the DRFZ have already gained some decisive insights into the various memory cells. We have shown that memory plasma cells and memory T cells survive in the bone marrow as resting cells that do not proliferate. Here they are kept alive by stromal cells that provide survival signals. Pathogenic memory cells also survive in inflamed tissue. We have found molecular differences between protective and pathogenic memory T cells – frequent reactivation leaves its mark. These differences now serve as a starting point for the development of new therapies which are as selective as possible. Together with our clinical partners at the Charité, we are successfully testing new therapeutic approaches against memory plasma cells in patients with systemic lupus erythematodes and other diseases in which pathogenic autoantibodies play a central role.

More detailed information on the different memory cells is provided in the profiles of the research groups working on immunological memory.

Further research topics