Portrait of Albert Einstein outdoors; Scharbeutz Portraits; Men

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Albert Einstein writing at desk Portraits; Men

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Albert Einstein Portraits; Men

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Portrait of the Beethoven Maennerchor (Men's Choir) Portraits Groups

Handwritten caption

Portrait of the Beethoven Maennerchor (Men's Choir) outside castle; Heidelberg Portraits Groups

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Portrait of the Beethoven Maennerchor (Men's Choir); Eisenach Portraits Groups

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Dr. Simberg, Rudolf Mosse, Richard Israel and other unidentified men hunting with Count Czarnecki Portraits; Children

Jagd beim Grafen Czarnecki

Friedrich Bergammer (Fritz Glueckselig) standing in the doorway of the gallery store M. Glueckselig & Son; 108 East 57th Street, New York Portraits Men

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Portrait of Heinrich Stahl standing at his desk; Berlin Portraits; Men

Signed lower right by photographer Casparius

Portrait of Heinrich Stahl seated at his desk; Berlin Portraits; Men

Signed lower right by photographer Casparius

Autographed portrait of Gabriel Beer-Hofmann Portraits Men

Signed: Zur Erinnerung! - Gabriel - October XXIX -

Portrait of Alexander Moissi in costume Portraits Men

Illegible handwriting bottom right

Of tolerance in mice and men : studies in APECED and Aire

Autoimmune diseases affect 5 % of the population and come in many forms, such as diabetes, rheumatoid arthritis and MS. However, how and why autoimmune diseases arise are not yet fully resolved. In this thesis, the onset of autoimmunity was investigated using both patient samples and a mouse model of autoimmunity. Autoimmune diseases are usually complex, due to a number of different causative genes and environmental factors. However, a few monogenic autoimmune diseases have been described, which are caused by mutations in only one gene per disease. One of such disease is called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) and is enriched in the Finnish population. The causative gene behind APECED is named AIRE from AutoImmune REgulator. How malfunction of just one gene product can cause the multitude of disease components found in APECED is not yet resolved. This thesis sought out to find out more about the functions of AIRE, in order to reveal why APECED and other autoimmune diseases arise and what goes wrong? Usually, immune cells are taught to distinguish between self and non-self during their development. That way, immune cells can fight off bacteria and microbes while leaving the tissues and organs of the host organism itself unharmed. In APECED, the development of immune cells called αβ T cells is incomplete. The cells are not able to fully distinguish between self and non-self. This leads to autodestruction of self tissues and autoimmune disease. One of the achievements of this thesis was the finding that the development of another set of T cells called γδ T cells is not affected by AIRE in mice or in men. Instead, we found that another type of immune cell important in tolerance, called the dendritic cell is defective in APECED patients and is not able to respond to microbial stimulus in a normal fashion. Finally, we studied Aire-deficient mice and found that autoantibodies expressed in the mice were not targeted against the same molecules as those found in APECED patients. This indicates differences in the autoimmune pathology in mice and men. More work is still required before we understand the mechanisms of tolerance and autoimmunity well enough to be able to cure APECED, let alone the more complex autoimmune diseases. Yet altogether, the findings of this thesis work bring us one step closer to finding out why and how APECED and common autoimmune diseases arise.