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BBB seminar: Silke Appel

Dendritic cells – the sentinels of the immune system

Silke Appel
Broegelmann Research Laboratory, The Gade Institute, University of Bergen

The processing and presentation of antigenic peptides on MHC class I and class II molecules are an important prerequisite of the immune system to be able to defend against invading pathogens and to fight tumor cells. In addition, the cells involved in this process have to differentiate between self and non-self peptides, which in the case of malfunction leads to autoimmune diseases.

Dendritic cells (DC) are recognized as the most potent antigen presenting cells with the unique ability to initiate and maintain primary immune responses. They are considered to be the sentinels of the immune system and can be found in almost every organ. They can be divided into various subsets, distinguished by their phenotype and function. DC acquire antigens in the periphery and migrate to the lymph nodes where antigen specific T lymphocytes recognize the presented antigens and mount an immune response. In this pathway, DC undergo distinct phenotypical and functional changes and develop from immature DC capable to take up antigens to mature cells able to process and present antigenic peptides. DC are also involved in launching humoral immunity by activating naive and memory B cells, and they have been shown to activate natural killer cells. Moreover, DC are pivotal in inducing tolerance. Immature DC within peripheral tissues constantly sample the surroundings for antigens, e.g. from apoptotic cells. After uptake of self-antigens and in the absence of an additional stimulus, DC remain immature and present self-peptide-MHC complexes to circulating naive T cells in peripheral lymphoid organs. In the case of autoreactivity, this will normally lead to anergy or deletion of the T cells, thereby inducing tolerance.

Due to the outstanding capacity of DC to process and present antigenic peptides to T lymphocytes, several approaches have been developed for their application in cancer immunotherapy. Yet the mechanisms involved in antigen processing and presentation that are responsible for their exceptional abilities remain to be clarified. The challenging and fascinating task remains to unravel the molecular and cellular mechanisms underlying a successful immune response as for tumor immunology and tolerance induction in autoimmune diseases. The aim is to reproduce the cascade of biological phenomena conducive to cancer regression as well as tolerance induction in clinical applications.