FIGURE 1. The mast cell as an integrator or amplifier of autoimmune responses.

From the following article:

Mast cells in autoimmune disease

Christophe Benoist and Diane Mathis

Nature 420, 875-878(19 December 2002)



The breakdown of tolerance and/or immunoregulatory mechanisms leads to autoimmune activation and recognition in the tissues. These responses, which are 'adaptative' in their anti-self specificity, generate primary 'innate' inputs into mast cells, such as immune complex binding to FcRs, and C3a and C5a anaphylatoxins of the complement pathway binding to specific receptors. The molecular route for direct 'bystander' activation of mast cells by T cells remains conjectural. The mast cell, owing to the abundance and diversity of secondary mediators in its granules, responds by activating a host of pathways, thus amplifying the local response. Vascular permeability is increased, allowing influx of additional molecules (antibody, complement). The adhesiveness of the vascular endothelium is increased, facilitating the homing of leukocytes (and in particular neutrophils) provoked by chemokine and TNF-alpha release. These leukocytes are also activated by the same cytokines. Mast cell mediators may be also involved in remodelling connective tissue, or in biasing secondary T-cell responses. Mast cell activation may also signal to local neuronal constituents by the release of NGF, serotonin or dopamine. Thus, the mast cell takes in what may be a low pro-inflammatory input and amplifies it to bring about a much wider response.