Abnormal immune response due to activation of antigen presenting cells

The recognition of peptides/MHC complexes at the cell surface of an antigen presenting cell by a specific T lymphocyte is not sufficient for triggering an immune response. Dendritic cells, that are the professional antigen presenting cells, need to be activated for initiating the immune response [1]. Signals delivered by pathogens through the toll receptors at the dendritic cell surface and signals generated in injured tissues activate dendritic cells. For example, platelets that con-stitutively express CD40L can interact with CD40 at the cell surface of dendritic cells leading to their activation in a bleeding tissue. Non immune tissue injury leads to necrotic death, release of reactive oxygen species, of heat shock proteins (HSP) and of lymphokines such as IL-1, TNFa, type I interferons, each being able to stimulate dendritic cells. Activation of dendritic cells results in upregulation of costimulatory molecules, in-tracellular formation of immunogenic MHC-class II peptide complexes and redistribution of MHC class II products from intracellular compartments to the plasma membrane [2], Many chemicals, including heavy metals, can directly activate dendritic cells [3], which certainly favors the development of a T-cell response. In addition, many chemicals may promote an inflammatory reaction, which indirectly contributes to dendritic cells maturation.

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