
Mast cells
Mast cells, seen here, originate from a precursor that circulates in the blood. It is not until this precursor migrates into our tissues that it develops into a fully mature mast cell that then takes up permanent residency here. Within the tissue mast cells are found in close proximity to blood vessels and peripheral nerves. Why do you think this is? Well, first of all, being close to the blood vessel may help to quickly detecting pathogens that are blood born, but mast cells are also full of granules that contain proteins and molecules, that are released instantly when the mast cell senses danger. Without delay, pre-stored mediators like histamine and TNF-α act on their surroundings, including nerves and blood vessels, to help repel the pathogen.
Mast cells can be activated in many ways, for example, directly by pathogens through their TLRs or through complement receptors. But the best known way of mast cell activation is through cross-linking of surface-bound IgE by an antigen, which is shown in this video. Watch how the mast cells’ mediators burst out. How do they affect the nearby blood vessel and which clinical symptom do you think this may result in?
What you didn’t see in this video was the high-affinity IgE receptor (FcεRI) on the mast cell surface that the IgE antibodies bound to. The mast cell degranulates when these high affinity IgE receptors are brought close enough together by two or more IgE antibodies that are binding to the same antigen. This is the process called cross-linking.
In the video clip, the mediators caused dilation and increased permeability of blood vessels that result in swelling and redness, both clinical symptoms that are part of the immediate phase response. But mast cell mediators can also induce tissue damage, smooth muscle contraction and mucus secretion. In extreme cases this can lead to anaphylaxis. After activation mast cells also produce and release leukotrienes, prostaglandins, Th2 cytokines like IL-4 and chemokines that help recruit other inflammatory cells into the tissue. What do you think will happen when these inflammatory cells arrive?