Immunology

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Description

Mast cells and basophils play a central role in inflammatory and immediate allergic reactions. They are able to release potent inflammatory mediators, such as histamine, proteases, chemotactic factors, cytokines and metabolites of arachidonic acid that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells.

Mast cells settle in connective tissues and usually do not circulate in the blood stream.

Basophils are the smallest circulating granulocytes with relatively the least known function. They arise in the bone marrow, and following maturation and differentiation, are released into the blood circulation. If they are adequately stimulated they may settle in the tissues.

Both mast cells and basophils contain special cytoplasmic granules which store mediators of inflammation. The extracellular release of the mediators is known as degranulation and may be induced by:

  • Physical destruction, such as high temperature, mechanical trauma, ionising irradiation, etc
  • Chemical substances, such as toxins, venoms, proteases;
  • Endogenous mediators, including tissue proteases, cationic proteins derived from eosinophils and neutrophils;
  • Immune mechanisms which may be IgE-dependent or IgE-independent. The former is elicited by aggregation of IgE bound to high-afinity receptors (FcRI) on the surface of these cells. Specific antigen (allergen) is responsible for the IgE aggregation. In the IgE-independent way, the anafylatoxins C5a, C3a and C4a are formed during activation of complement. Then, the degranulation is triggered through C5a-receptors on the surface of mast cells and basophils.

Basophils are the least common of the granulocytes, representing about 1% of circulating leukocytes. They contain large cytoplasmic granules which obscure the cell nucleus under the microscope. However, when unstained, the nucleus is visible and it usually has 2 lobes. A cell in tissues, the mast cell, has many similar characteristics. For example, both cell types store histamine, a chemical that is secreted by the cells when stimulated in certain ways (histamine causes some of the symptoms of an allergic reaction). Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed.

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Discussion

The number of basophils and mast cells increase at sites of inflammation. To reach these areas, basophils must migrate from the blood into tissue sites. A crucial step in this process is the adherence of cells to the endothelium. Cell adherence is mediated by several families of adhesion molecules and adhesion receptors in the surface of basophils and mast cells that can mediate binding to other cell and to the extracellular matrix (ECM) glycoproteins. Upon stimulation, basophils and mast cells release cytokines, including Tumor Necrosis Factor and Interleukin-4 (IL-4), that can modulate adhesion molecules on endothelial cells.

Recent evidence suggests that basophils are an important source of the cytokine, Interleukin-4 (IL-4), perhaps more important than T cells. Interleukin-4 is considered one of the critical cytokines in the development of allergies and the production of IgE antibody by the immune system.

Activated endothelial cells express the Intercellular adhesion molecules (ICAMs), [Endothelial-Leukocyte Adhesion Molecule (ELAM-1)]] and [Vascular cell adhesion molecule (VCAM-1)]? on their cell surface. Human basophils express integrins as receptors for these molecules.

When activated, basophils secrete histamine, several proteoglycans, lipid mediators like leukotrienes, and several cytokines. Histamine and proteoglycan are pre-stored in the cell's granules while the other secreted substances are newly generated. Each of these substances contributes to inflammation.

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