The role of<unk> s in the development of allergy.<unk> s play a key role in the inflammatory process. When activated, a<unk>  can either selectively release (piecemeal degranulation) or rapidly release (anaphylactic degranulation) "mediators", or compounds that induce inflammation, from storage granules into the local microenvironment.<unk> s can be stimulated to degranulate by allergens through cross-linking with immunoglobulin E receptors (e.g., FcεRI), physical injury through pattern recognition receptors for damage-associated molecular patterns (DAMPs), microbial pathogens through pattern recognition receptors for pathogen-associated molecular patterns (PAMPs), and various compounds through their associated G-protein coupled receptors (e.g., morphine through opioid receptors) or ligand-gated ion channels. Complement proteins can activate membrane receptors on<unk> s to exert various functions as well.<unk> s express a high-affinity receptor (FcεRI) for the Fc region of IgE, the least-abundant member of the antibodies. This receptor is of such high affinity that binding of IgE molecules is in essence irreversible. As a result,<unk> s are coated with IgE, which is produced by plasma cells (the antibody-producing cells of the immune system). IgE antibodies are typically specific to one particular antigen. In allergic reactions,<unk> s remain inactive until an allergen binds to IgE already coated upon the cell. Other membrane activation events can either prime<unk> s for subsequent degranulation or act in synergy with FcεRI signal transduction. In general, allergens are proteins or polysaccharides. The allergen binds to the antigen-binding sites, which are situated on the variable regions of the IgE molecules bound to the<unk>  surface. It appears that binding of two or more IgE molecules (cross-linking) is required to activate the<unk> . The clustering of the intracellular domains of the cell-bound Fc receptors, which are associated with the cross-linked IgE molecules, causes a complex sequence of reactions inside the<unk>  that lead to its activation. Although this reaction is most well understood in terms of allergy, it appears to have evolved as a defense system against parasites and bacteria.<unk>  mediators A unique, stimulus-specific set of<unk>  mediators is released through degranulation following the activation of cell surface receptors on<unk> s. Examples of mediators that are released into the extracellular environment during<unk>  degranulation include: * serine proteases, such as tryptase and chymase * histamine (2–5 picograms per<unk>  * serotonin * proteoglycans, mainly heparin (active as anticoagulant) and some chondroitin sulfate proteoglycans * adenosine triphosphate (ATP) * lysosomal enzymes * β-hexosaminidase * β-glucuronidase * arylsulfatases * newly formed lipid mediators (eicosanoids): * thromboxane * prostaglandin D2 * leukotriene C4 * platelet-activating factor * cytokines * TNF-α * basic fibroblast growth factor * interleukin-4 * stem cell factor * chemokines, such as eosinophil chemotactic factor * reactive oxygen species Structure of histamine Histamine dilates post-capillary venules, activates the endothelium, and increases blood vessel permeability. This leads to local edema (swelling), warmth, redness, and the attraction of other inflammatory cells to the site of release. It also depolarizes nerve endings (leading to itching or pain). Cutaneous signs of histamine release are the "flare and wheal"-reaction. The bump and redness immediately following a mosquito bite are a good example of this reaction, which occurs seconds after challenge of the<unk>  by an allergen. The other physiologic activities of<unk> s are much less-understood. Several lines of evidence suggest that<unk> s may have a fairly fundamental role in innate immunity: They are capable of elaborating a vast array of important cytokines and other inflammatory mediators such as TNF-α; they express multiple "pattern recognition receptors" thought to be involved in recognizing broad classes of pathogens; and mice without<unk> s seem to be much more susceptible to a variety of infections.<unk>  granules carry a variety of bioactive chemicals. These granules have been found to be transferred to adjacent cells of the immune system and neurons in a process of transgranulation via<unk>  pseudopodia. In the nervous system Unlike other hematopoietic cells of the immune system,<unk> s naturally occur in the human brain where they interact with the neuroimmune system. In the brain,<unk> s are located in a number of structures that mediate visceral sensory (e.g. pain) or neuroendocrine functions or that are located along the blood–cerebrospinal fluid barrier, including the pituitary stalk, pineal gland, thalamus, and hypothalamus, area postrema, choroid plexus, and in the dural layer of the meninges near meningeal nociceptors.<unk> s serve the same general functions in the body and central nervous system, such as effecting or regulating allergic responses, innate and adaptive immunity, autoimmunity, and inflammation. Across systems,<unk> s serve as the main effector cell through which pathogens can affect the gut–brain axis. In the gut In the gastrointestinal tract, mucosal<unk> s are located in close proximity to sensory nerve fibres, which communicate bidirectionally. When these<unk> s initially degranulate, they release mediators (e.g., histamine, tryptase, and serotonin) which activate, sensitize, and upregulate membrane expression of nociceptors (i.e., TRPV1) on visceral afferent neurons via their receptors (respectively, HRH1, HRH2, HRH3, PAR2, 5-HT3); in turn, neurogenic inflammation, visceral hypersensitivity, and intestinal dysmotility (i.e., impaired peristalsis) result. Neuronal activation induces neuropeptide (substance P and calcitonin gene-related peptide) signaling to<unk> s where they bind to their associated receptors and trigger degranulation of a distinct set of mediators (β-Hexosaminidase, cytokines, chemokines, PGD2, leukotrienes, and eoxins). Figure 1: Mediator release from<unk> s Figure 2: Model of genesis of<unk>  secretory granules Figure 3: Lipid body biogenesis Table 2: Stimuli-selective mediator release from<unk> s
Mast cell
T cell
Reactive lymphocyte
Dendritic cell
Natural killer cell
Prolymphocyte
Nonspecific immune cell
Basophil