Quo Vadis: Aberrations in the Development of Dendritic Cells in the Autoimmunity-Prone Non-Obese Diabetic Mouse

Immune system protects us from harmful microbes and tumor development. At the same time, the immune system makes sure that the unnecessary immune reaction against harmless foreign substances (known as antigens) or self-originating structures (self-antigens) either does not occur or is stopped before it induces irreparable damage to a healthy organ. Therefore, the immune system is able to make a distinction between the “dangerous” and the “harmless” irrespective of its origin. If a “dangerous” is encountered, defense mechanisms are activated that generate an inflammation. Elimination of the inflammation inducers leads to a deceleration of inflammation and a wound healing, which is actively regulated. The response against harmless antigens (either foreign or self) is also actively suppressed and is called tolerance. The mechanisms utilized for the controlled activation and inhibition of the inflammation and for the tolerance acquisition enable the balanced function of the immune system, called immune regulation. In some situations the immune regulation can be disturbed and the immune system starts to destroy healthy cells leading to an irreparable damage. This action of the immune system is called an autoimmune reaction and as a consequence an autoimmune disease develops. Such a process directed against b-cells in the islets of Langerhans in the pancreas leads to the autoimmune disease termed type 1 diabetes (also known as a sugar disease). Macrophages (Mf) and dendritic cells (DC) importantly contribute to the proper function of the immune system. These two cell types comprise a heterogeneous group of cells called mononuclear phagocytes, which differ in the phenotype, function or the origin. They are sentinels that reside in all organs and are the first that encounter the infectious agents, transformed cells, or some other harmful substances. As an immediate reaction, they activate the inborn immunity and start an inflammatory reaction that subsequently leads to the activation of other immune forces. Later, they also mediate the reduction of the inflammation and help the wound healing. In addition, they are also important for the activation of the specific immune forces (including tolerance): DC take up the antigen, present it to other cells of the immune system and transduce a signal whether that antigen should be destroyed or ignored. Taken together, mononuclear phagocytes can perform several different function and enable a balanced function of the immune system, called homeostasis.