Dendritic Cells: Master Regulators of The Immune System

There are many reasons why you should know something about the dendritic cells:

1. They represent the sentinel of you body, constantly on the alert, attacking at the first sign of an intrusion by infectious microrganisms.

2. They constantly sense the internal environment of the body to fine tune the immune response, initiating a strong reaction to a nascent tumor or silencing an overreaction of the immune system that may lead to the progress of an autoimmune disease.

3. It is very likely that the next big vaccine will be based on technologies exploiting the knowledge gained through the study of the mechanisms of dendritic cell function.

4. The first immunotherapy of a cancer may soon be introduced to the market if the expectation about the ne drug Provenge hold true. The most important ingredient in this drug is: dendritic cells.

It is however good to be prudent about the prospects for this new drug.

Dendritic cells belong to a family of immune cells called phagocytes that specialized in finding and "eating" bacteria, viruses, and injured or dead body cells. They are cells that can be found at different stages of maturation. They derive from progenetor (parent!) cells that are of either lymphoid or myeloid origin and can be generated in vitro from fresh blood. This process takes almost a week and requires special media enriched with the cytokines interleukin 4 and GM-CSF

What distinguish dendritic cells from the other phagocytes is their exceptional ability to reprocess the phagocytozed /eaten antigens and present them in a framework that alert and activate a group of cells called naïve T cells.

During their interactions with other cells of the immune system, and especially T cells, dendritic cells use special receptors and ligands (receptor counterpart) that allow them to communicate specific information to these cells. These receptors, differentially expressed on dendritic cells and other cells, are designated by CD numbers from CD1 all the way through CD300. The MHC classI and ClassII molecules are the primary receptor that are used in complex with the processed peptide antigens in order to engage the T cell receptors (TCR) on T cells. Other co-receptors are also used in this interaction. the most prominent are those belonging to the B-7 family like CD86, CD80,..etc). Some of these proteins are co-stimulator and others are inhibitors of TCR activation.

The specific cell surface receptors on DC serve as markers that allow the identification of these cells in the body tissues like blood and spleen. These specific markers like CD11c can be tagged be specific antibodies labeled with fluorescent colors that can be detected by fluorescent microscopy or flow activated cell sorting (FACS) analysis.

The discovery of the co-stimulatory B7/CD28 interaction led to the establishment of the "two-signal" model for lymphocyte activation which stipulates that a lymphocyte requires two distinct signals in order for full activation to take place.

Besides direct contacts immune cells interact through the release of cytokines and kemokines, which are soluble, chemical mediators released in the extracellular environment and which acts on neighboring cells by binding to special surface expressed receptors.