Immunoglobulins mast cells

The role of NFAT in the immune system is not restricted to T cells. NFAT proteins are also expressed in other cells of the immune system, such as B cells, NK cells, and mast cells, where they have been shown to regulate the expression of cytokines, cell surface receptors, and immunoglobulins [4, 5]. 

Type I allergic reactions are inappropriate immune responses to an allergen with preferential synthesis of immunoglobulin E (IgE), a special antibody class, which binds to mast cells and basophilic granulocytes via Fee receptors. Binding of the allergen to the cell-bound IgE initiates the rapid release of allergic mediators, most prominently histamine, and the de novo synthesis of arachidonic acid metabolites and cytokines, which are responsible for the clinical symptoms. 

Price KS, Friend DS, Mellor EA, De Jesus N, Watts GF, Boyce JA. CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. Am J Respir Cell Mol Biol 2003 28(4) 420-427. 

Immunoglobulin receptors, such as the high affinity receptor for IgE, are present on mast cells and bloodbome basophils. These receptors play an important role in hypersensitivity and the initiation of acute inflammatory responses. 

The answers are 25-e, 26-b, 27-a. (Hardmanr pp 67—68. Katzung, pp 30, 134.) Anaphylaxis refers to an acute hypersensitivity reaction that appears to be mediated primarily by immunoglobulin E (IgE). Specific antigens can interact with these antibodies and cause sensitized mast cells to release vasoactive substances, such as histamine. Anaphylaxis to penicillin is one of the best-known examples the drug of choice to relieve the symptoms is epinephrine. 

IgE is known as a cytophilic immunoglobulin because of its ability to bind to cells, which may account for its low concentration in body fluids. When IgE reacts with an antigen it causes degranulation of the mast cell to which it is bound, with the release of vasoactive amines such as histamine. This process may well be helpful in initiating the inflammatory response but in allergic individuals the reaction is excessive and leads to a hypersensitive or over-reactive state. 

Tanaka S. Takasu Y, Mikura S, Satoh N, Ichikawa A Antigen-independent induction of histamine synthesis by immunoglobulin E in mouse bone marrow-derived mast cells. J Exp Med 2002 196 229-235. 

Histamine, an important mediator (local signaling substance) and neurotransmitter, is mainly stored in tissue mast cells and basophilic granulocytes in the blood. It is involved in inflammatory and allergic reactions. Histamine liberators such as tissue hormones, type E immunoglobulins (see p. 300), and drugs can release it. Histamine acts via various types of receptor. Binding to Hi receptors promotes contraction of smooth muscle in the bronchia, and dilates the capillary vessels and increases their permeability. Via H2 receptors, histamine slows down the heart rate and promotes the formation of HCl in the gastric mucosa. In the brain, histamine acts as a neurotransmitter. 

Mechanical destruction of cells, as it occurs as a result of a trauma, is the most unspecific way of histamine release. Another important mechanism are allergic reactions. The triggering reaction is the binding of an antigen at immunoglobulin E (IgE) antibodies present at the surface of mast cells. A series of reactions, one of which is a calcium influx, leads... 

Mechanism of Action A monoclonal antibody that selectively binds to human immunoglobulin E (IgE) preventing it from binding to the surface of mast cells and basophils. Therapeutic Effect Prevents or reduces the number of asthmatic attacks. Pharmacokinetics Absorbed slowly after subcutaneous administration, with peak concentration in 7-8 days. Excreted in the liver, reticuloendothelial system, and endothelial cells. Half-life 26 days. 

Pramod, S. N., Venkatesh, Y. P, Mahesh, P. A. (2007). Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E. Clin. Exp. Immunol., 748,391 01. 

In nature, mammalian antibodies occur in five distinct classes IgG, IgA, IgM, IgD, and IgE. These differ in structure, size, amino acid composition, charge, and carbohydrate components. The basic structure of each of the classes of immunoglobulins consists of two identical polypeptide chains linked by disulfide bonds to two identical heavy chains. Differences between classes and subclasses are determined by the makeup of the respective heavy chains. IgG is the major serum immunoglobulin and occurs as a single molecule IgA also occurs as a single molecule but also polymerizes, primarily as a dimer and also associates with a separate protein when secreted. IgM occurs in the serum as a pentamer, with monomers linked by disulfide bonds and the inclusion of an additional polypeptide component, the J-chain. IgD and IgE occur primarily as membrane-bound monomers on -cells, or basophils and mast cells, respectively. 

Immunoglobulins can also be receptors. For example, molecules of IgE bound to basophils and the related mast cells of tissues serve as receptors for allergens. Binding of an allergen to the IgE molecules stimulates the release of granules containing histamine and other substances (Chapter 31). 

Histamine Release. Histamine release is mainly caused by cross-linking of immunoglobulin E on the mast cell surface by antigens. Basophil degranulation is caused mainly by histamine-releasing factors produced by inflammatory cells, such as neutrophils, platelets, and eosinophils. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues. 

Fig. 9.3. Immunoglobulin E (IgE) and mast cell activation are important components of the mammalian response to cestode infections (ADCC, antibody dependent cell-mediated cytotoxicity Ag, antigen EO, eosinophils Feel, high affinity receptor for Fc portion of IgE LTs, leukotrienes Mac, macrophages NO, nitric oxide PGs, prostaglandins TNFa, tumour necrosis factor alpha).

Le Coniat M, Kinet JP, Berger R. The Human genes for the alpha and gamma subunits of the mast cell receptor for immunoglobulin E are located on human chromosome band lq23. Immunogenetics 1990 32(3) 183—186. 

---