The Story of Itch
Skin itch, also known as pruritus, is the major symptom in skin diseases with a variety of etiologies and pathophysiologies. Recent studies have demonstrated that peripheral mediators other than histamines are involved in the induction of itch. (Paus et al., 2007)
Just under the skin are capillaries carrying blood with its circulating red cells and a variety of white blood cell types. Just outside of the capillaries, in the tissue of the dermis, are specialized immune cells called MAST CELLS, the major cells responsible for the itch phenomenon. Mast cells and basophils play a central role in inflammatory and immediate allergic reactions.
When the skin gets itchy and red from contact with an “allergen”, it’s because of how the body’s mast cells respond to the allergen.
Langerhans cells are immune cells and form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface of other cells of the immune system, thus functioning as antigen-presenting cells, presenting the allergen to the mast cells.
The structure of human skin and epidermis.
The three layers of skin are epidermis, dermis, and hypodermis. The epidermis consists of four layers: stratum basale (SB), stratum spinosum (SS), stratum granulosum (SG) and stratum corneum (SC). The epidermis also contains some melanocytes and Langerhans cells.
Potential contributions of mast cells during innate and acquired immunity, and in other biological responses (Galli and Nakae, 2003).
Mast Cells
Mast cells are covered with molecules of Immunoglobulin E antibody (IgE).
If an antigen (allergen, known or unknown) gets under the skin of an allergic host, the antigens cause mast cells to go berserk. Antigens stick to the mast cell IgE antibodies, causing granules in the mast cell to leak out their contents into the surrounding tissue.
This releases a host of inflammatory materials – histamine, leukotrienes, tumor necrosis factor-alpha (TNF-a), interleukin-4, potent proteases (such as tryptase), metabolites of an arachidonic acid such as prostaglandins and leukotrienes. At later stages, numerous inflammatory cytokines and chemokines are produced as a result of gene transcription.
These materials cause fluid to leak from the capillaries and white cells including neutrophils, T cells, and eosinophils to leave the circulation. The end result is a “local inflammatory response”, a red, itchy spot/area (Yosipovitch and Fleischer, 2003, Paus et al., 2007, Beaven and Hundley. 2003)
Interacting with various receptors on the mast cell surface, multiple agents (including products of pathogens, as well as elements of innate, humoral and cellular immunity) can activate mast cells to release a large panel of mediators.
Suitably activated mast cells can release lipid mediators (such as leukotrienes B4 and C4 and prostaglandin D2 and granule-associated preformed mediators (including histamine, serotonin (in murine species), tryptases and chymases, and heparin and other proteoglycans), as well as TNF and many other cytokines, chemokines and growth factors.
Through diverse effects on many different cell types, these products can directly or indirectly result in both acute changes and chronic effects.
References
1. Beaven, M. A. and T. R. Hundley. 2003. Mast cell related diseases: Genetics, signaling pathways, and novel therapies. In ASignal Transduction and Human Disease Eds T. Finkel and J. S. Gutkind. John Wiley & Sons, Hoboken, NJ. 307-355
2. He, S., Mceuen, R., Blewett, S. A., Ping, L., Buckley, M.G., Leufkens, P., Walls, A. F., (2003) Biochemical pharmacology (Biochem. pharmacol.) 2003, 65:6, 1007-1015
3. Galli, S.J. and Nakae, S. (2003). Mast cells to the defence. Nature Immunology 4, 1160 – 1162
4. Yosipowitch, G., and Fleischer A. (2003) Itch associated with skin disease: advances in pathophysiology and emerging therapies Am J Clin Dermatol. 4(9), 617-22
5. Paus, R., Schmeiz, M., Tamas, B., and Steinhoff, M. (2007) Frontiers in prurritus research: scratching the brain for more effective itch therapy. The journal of Clinical investigation, 116 (5), 1174-1184)