Structure and Distribution of Mast Cells - Mast cells are granulated cells that contain histamine and heparin. - They have a round nucleus, unlike basophil granulocytes. - Mast cells and basophils share a common precursor in bone marrow expressing the CD34 molecule. - Mast cells settle in different tissue sites, which determines their characteristics. - Mast cells are present in most tissues, particularly surrounding blood vessels, nerves, and lymphatic vessels.

Function and Mediators of Mast Cells - Mast cells play a key role in the inflammatory process. - They can release inflammatory mediators when activated. - Mast cells can be stimulated by allergens, physical injury, microbial pathogens, and various compounds. - They express a high-affinity receptor (FcεRI) for the Fc region of IgE. - Histamine released by mast cells dilates blood vessels and increases permeability. - Mast cells can release a variety of cytokines and inflammatory mediators. - Mast cell granules carry bioactive chemicals that can be transferred to adjacent cells. - Histamine release causes local edema, redness, and itching or pain. - Mast cells may have a fundamental role in innate immunity.

Mast Cells in the Nervous System - Mast cells naturally occur in the human brain and interact with the neuroimmune system. - They are located in structures involved in visceral sensory functions and along the blood-cerebrospinal fluid barrier. - Mast cells in the brain serve similar functions as in the body, including allergic responses, immunity, and inflammation. - Mast cells play a role in the gut-brain axis and can be affected by pathogens. - Mast cells in the nervous system are located near meningeal nociceptors.

Mast Cells in the Gut - Mucosal mast cells in the gastrointestinal tract are located near sensory nerve fibers. - Mast cell degranulation releases mediators that activate and sensitize nociceptors. - Histamine, tryptase, and serotonin are examples of mediators released by mast cells in the gut. - Mast cells in the gut communicate bidirectionally with sensory nerve fibers. - Mast cells in the gut play a role in regulating pain and inflammation.

Physiology and Activation of Mast Cells - FcεR1 is a tetramer composed of one alpha (α) chain, one beta (β) chain, and two gamma (γ) chains. - IgE binds to the alpha (α) chain of FcεR1, initiating signal transduction through ITAM motifs on the beta (β) and gamma (γ) chains. - Type 2 helper T cells (Th2) and certain cell types lack the beta (β) chain, relying solely on the gamma (γ) chain for signaling. - The assembly of the alpha (α) chain with the beta (β) and gamma (γ) chains allows the complex to be exported to the plasma membrane. - In humans, only the gamma (γ) complex is needed to counterbalance the alpha (α) chain ER retention. - FcεR1 is a high-affinity IgE receptor found on the surface of mast cells. - It is a tetramer consisting of one alpha (α) chain, one beta (β) chain, and two identical gamma (γ) chains. - The alpha (α) chain contains the binding site for IgE and has two domains similar to Ig. - The beta (β) chain has a single ITAM in the cytoplasmic region, while each gamma (γ) chain also has an ITAM. - Phosphorylation of the ITAMs by tyrosine initiates the signaling cascade from the receptor. - Allergen-mediated FcεR1 cross-linking signals resemble the signaling event in antigen binding to lymphocytes. - Lyn tyrosine kinase is associated with the cytoplasmic end of the FcεR1 beta (β) chain. - Antigen cross-linking leads to phosphorylation of the ITAMs on the beta (β) and gamma (γ) chains. - Phosphorylated ITAMs recruit Syk tyrosine kinase, which activates multiple proteins in the signaling cascade. - Activation of other proteins in the FcεR1-mediated signaling cascade occurs due to antigen-stimulated phosphorylation. - Linker for activation of T cells (LAT) is an adaptor protein activated by Syk phosphorylation. - Phospholipase C gamma (PLCγ) becomes phosphorylated when bound to LAT, leading to phosphatidylinositol bisphosphate breakdown. - Phosphorylation of PLCγ yields inositol trisphosphate (IP3) and diacylglycerol (DAG). - IP3 elevates calcium levels, while DAG activates protein kinase C (PKC). - PKC phosphorylates myosin light-chain, facilitating granule movements and fusion with the plasma membrane. - MRGPRX2 is a G-protein-coupled receptor specific to human mast cells. - It plays a role in recognizing pathogen-associated molecular patterns (PAMPs) and initiating an antibacterial response. - MRGPRX2 can bind to competence stimulating peptide (CSP) 1, a quorum sensing molecule produced by Gram-positive bacteria. - Activation of MRGPRX2 leads to mast cell activation and release of antibacterial mediators. - MRGPRX2 is a potential therapeutic target and can be activated using the agonist compound 48/80 to control bacterial infection.

Functions and Disorders of Mast Cells - Mast cells release histamine during anaphylaxis, causing vasodilation and potentially life-threatening shock. - Mast cells are implicated in autoimmune and inflammatory disorders of the joints, such as rheumatoid arthritis. - Mastocytosis is a rare disorder characterised by an excessive number of mast cells. - Mutations in the c-Kit gene are associated with mastocytosis. - Mast cell tumors, known as mastocyt