Mast Cells- Definition, Structure, Immunity, Types, Functions

Mast cells are a type of white blood cell that play a vital role in the immune system. They are found in various tissues throughout the body, especially in the skin, mucous membranes, and connective tissues. Mast cells are involved in both innate and adaptive immunity, as well as in allergic reactions and inflammation. Mast cells have the ability to release various substances, called mediators, that can affect the function of other cells and organs. Some of these mediators include histamine, heparin, cytokines, and proteases. Mast cells can also interact with other immune cells, such as B cells, T cells, dendritic cells, and eosinophils.

Mast cells are derived from hematopoietic stem cells in the bone marrow. They undergo differentiation and maturation in the peripheral tissues under the influence of various factors, such as cytokines and growth factors. Mast cells can be classified into two main types: mucosal mast cells and connective tissue mast cells. These two types differ in their location, morphology, granule content, and response to stimuli. Mast cells can also be further subdivided into subtypes based on their expression of surface markers and receptors.

Mast cells are important for maintaining the homeostasis of the body and protecting it from pathogens and foreign substances. However, mast cells can also contribute to pathological conditions when they are overactivated or dysregulated. For example, mast cells can cause allergic reactions, such as anaphylaxis, asthma, urticaria, and rhinitis, by releasing excessive amounts of histamine and other mediators. Mast cells can also be involved in chronic inflammatory diseases, such as atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis, by producing pro-inflammatory cytokines and chemokines. Furthermore, mast cells can influence tumor growth and angiogenesis by secreting growth factors and proteases.

In this article, we will discuss the structure, immunity, types, and functions of mast cells in more detail. We will also explore some of the clinical implications of mast cell activation and dysfunction.

Mast cells are specialized immune cells that are derived from hematopoietic stem cells in the bone marrow. They migrate to various tissues and organs, where they mature and differentiate into different types depending on the local microenvironment. Mast cells have a characteristic appearance under the microscope, which can be summarized as follows:

• Shape and size: Mast cells are oval or irregularly shaped cells with a diameter of about 10 to 15 micrometers. They have a single central nucleus that is often obscured by the numerous cytoplasmic granules. They also have small, finger-like projections called microvilli that extend from the plasma membrane and help in sensing the extracellular environment.
• Cytoplasmic granules: Mast cells are filled with small secretory granules that contain various inflammatory mediators, such as histamine, heparin, cytokines, chemokines, and proteases. The granules are metachromatic, meaning they stain differently depending on the dye used. The granules can be released by exocytosis when mast cells are activated by stimuli such as allergens, pathogens, or physical injury. The release of granules is called degranulation and it triggers an immediate hypersensitivity reaction that involves vasodilation, increased vascular permeability, smooth muscle contraction, and recruitment of other immune cells.
• Plasma membrane receptors: Mast cells express various receptors on their plasma membrane that allow them to recognize and respond to different signals. The most important receptor is the high-affinity IgE receptor (FcεRI), which binds to the Fc region of circulating IgE antibodies. IgE antibodies are produced by B cells in response to specific antigens and they sensitize mast cells for subsequent exposure to the same antigen. When the antigen binds to the IgE-FcεRI complex on mast cells, it triggers a cascade of intracellular signaling events that lead to degranulation and cytokine production. Other receptors on mast cells include toll-like receptors (TLRs), complement receptors (CRs), cytokine receptors (CRs), and adhesion molecules (AMs).

Mast cells can be classified into two main types based on their location and phenotype: connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs). CTMCs are found mainly in the skin, subcutaneous tissue, peritoneum, and synovium. They have large and densely packed granules that contain histamine, heparin, tryptase, chymase, carboxypeptidase A3, cathepsin G, and TNF-α. MMCs are found mainly in the mucosal surfaces of the respiratory, gastrointestinal, and genitourinary tracts. They have smaller and less dense granules that contain histamine, heparin, tryptase, TNF-α, IL-4, IL-5, IL-6, IL-13, and CCL2. MMCs also express CD25 (the alpha chain of the IL-2 receptor) on their surface.

Mast cells can also change their phenotype and function depending on the stimuli they encounter. For example, mast cells can undergo phenotypic switching from CTMCs to MMCs or vice versa under certain conditions. Mast cells can also acquire new functions such as antigen presentation or phagocytosis by expressing new receptors or molecules.

Mast cells are dynamic and versatile immune cells that play a crucial role in both innate and adaptive immunity. They can sense and respond to a variety of stimuli and modulate the inflammatory response accordingly. However, they can also cause unwanted effects such as allergic reactions or chronic inflammation when they are overactivated or dysregulated.

Mast cells are important players in both innate and adaptive immunity. They can sense and respond to various pathogens, allergens, and environmental stimuli by releasing a variety of mediators that modulate inflammation, tissue repair, and immune regulation.

Mast cells can recognize pathogens through different receptors on their surface, such as toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin receptors (CLRs), and Fc receptors. These receptors can trigger different signaling pathways that lead to the activation and degranulation of mast cells.

Degranulation is the process of releasing the preformed granules that contain histamine, heparin, proteases, cytokines, chemokines, and growth factors. These mediators can have various effects on the surrounding cells and tissues, such as vasodilation, increased vascular permeability, smooth muscle contraction, mucus secretion, recruitment of inflammatory cells, and modulation of antigen presentation.

Mast cells can also synthesize and release new mediators in response to stimulation, such as prostaglandins, leukotrienes, platelet-activating factor (PAF), nitric oxide (NO), and reactive oxygen species (ROS). These mediators can amplify the inflammatory response and regulate the function of other immune cells.

Mast cells can interact with other immune cells through direct cell-cell contact or through soluble mediators. Mast cells can activate or inhibit dendritic cells, T cells, B cells, macrophages, neutrophils, eosinophils, basophils, natural killer (NK) cells, and natural killer T (NKT) cells. Mast cells can also influence the differentiation and polarization of Th1, Th2, Th17, and Treg cells.

Mast cells play a crucial role in allergic reactions, which are hypersensitive immune responses to harmless antigens. Mast cells bind to IgE antibodies that are specific for the allergen and cross-link them upon exposure to the allergen. This triggers a rapid degranulation of mast cells and the release of histamine and other mediators that cause the symptoms of allergy, such as itching, sneezing, wheezing, swelling, and anaphylaxis.

Mast cells also participate in chronic inflammatory diseases, such as asthma, atopic dermatitis, rheumatoid arthritis, inflammatory bowel disease (IBD), and multiple sclerosis (MS). Mast cells can contribute to the pathogenesis of these diseases by releasing pro-inflammatory mediators that sustain the inflammation and tissue damage.

Mast cells have also been implicated in anti-tumor immunity. Mast cells can exert anti-tumor effects by releasing cytotoxic mediators that kill tumor cells directly or by activating other immune cells that target tumor cells. Mast cells can also exert pro-tumor effects by releasing angiogenic mediators that promote tumor growth and metastasis or by suppressing anti-tumor immunity.

Mast cells are versatile immune cells that have both beneficial and detrimental roles in health and disease. They can modulate the immune response depending on the type and context of the stimulus. Understanding the function and regulation of mast cells may provide new insights into the mechanisms of immunity and inflammation and may lead to novel therapeutic strategies for various diseases.

Types of Mast Cells

Mast cells in human beings can be differentiated into two types; mucosal and connective tissue mast cells.

The connective tissue mast cells are found primarily in the loose connective tissue and skin, but these can be found in other connective tissues as well.

The mucosal type mast cell is found in the gastrointestinal mucosa and peripheral airways.

The exact factor that causes the differentiation of mast cells into the two types is not yet completely known.

However, both of these types of mast cells can be activated by allergens and other nonallergic signals. Both types also have the IgE receptors responsible for the activation of degranulation of the cells.

The difference between the two mast cells can be observed in their response to nonallergic signals, the mediators and their release, their proteoglycan constituents, and the makeup of the granular enzymes.

The distinction between the two types of cells can be made easily in the case of rodents as these stains differently differ in size and are found in different tissues.

The differentiation between the mast cells in humans can be made through the presence of chymase, a chymotryptic protease.

The protease is only present in connective tissue mast cells, but the enzyme tryptic protease or tryptase is found in all human mast cells.

Mast cells are involved in various physiological and pathological functions in the body. Some of the main functions of mast cells are:

• Regulation of vascular permeability and blood flow. Mast cells release histamine, heparin, and other vasoactive substances that cause dilation and increased permeability of blood vessels. This allows the influx of fluid and immune cells to the site of inflammation or injury. Mast cells also secrete angiogenic factors that promote the formation of new blood vessels.
• Defense against pathogens and parasites. Mast cells recognize and respond to various microbial and parasitic antigens through their surface receptors, such as toll-like receptors (TLRs) and Fc receptors. Upon activation, mast cells release cytokines, chemokines, and antimicrobial peptides that recruit and activate other immune cells, such as neutrophils, macrophages, and eosinophils. Mast cells also produce reactive oxygen species (ROS) and nitric oxide (NO) that directly kill or inhibit the growth of pathogens. Mast cells can also phagocytose and present antigens to T cells and B cells, thus facilitating adaptive immunity.
• Modulation of allergic and anaphylactic reactions. Mast cells are the key effector cells in IgE-mediated allergic responses. When mast cells bind to IgE antibodies that are specific for an allergen, they undergo degranulation and release histamine, leukotrienes, prostaglandins, and other mediators that cause bronchoconstriction, vasodilation, edema, itching, sneezing, and other symptoms of allergy. Mast cells also secrete cytokines that promote the differentiation and activation of Th2 cells, which in turn stimulate B cells to produce more IgE antibodies. In severe cases, mast cell activation can lead to anaphylaxis, a life-threatening systemic reaction characterized by hypotension, shock, and airway obstruction.
• Participation in tissue repair and remodeling. Mast cells play a role in wound healing and tissue regeneration by releasing growth factors, such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF). These factors stimulate the proliferation and migration of fibroblasts, endothelial cells, smooth muscle cells, and other cell types involved in tissue repair. Mast cells also secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that regulate the degradation and synthesis of extracellular matrix components. Moreover, mast cells modulate the balance between pro-inflammatory and anti-inflammatory cytokines that influence the resolution of inflammation and fibrosis.
• Involvement in neuroimmune interactions. Mast cells are located close to nerve endings and can communicate with neurons through direct contact or through the release of neurotransmitters, such as histamine, serotonin, substance P, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). These substances can affect the function of sensory neurons, motor neurons, and central nervous system neurons. Mast cells can also respond to neuronal signals by altering their secretion of mediators or by changing their phenotype. Mast cell-neuron interactions are implicated in various neurological disorders, such as migraine, multiple sclerosis, autism spectrum disorder, chronic pain, and depression.

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