Allergy and Allergic Diseases: The New Mechanisms and Therapeutics
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Explore now. The immune system is unique in that it can very selectively discriminate between self and nonself, leaving self alone while rapidly processing and destroying nonself foreign antigens in a primary immune response. In addition, a functioning immune system remembers previous encounters with these foreign antigens, resulting in a more vigorous and rapid secondary response called immunologic memory. These responses depend on both T cells dependent on the thymus gland for function and, when specific antibody is made, B cells which ultimately differentiate into antibody secreting plasma cells.
These cells are present in bone marrow, lymphoid organs i. Many of these lymphoid cells look alike when viewed under a microscope. They can be categorized by the presence of specific cell surface markers called clusters of differentiation CD. Each CD marker is given a specific number and is found on certain cell types.
Thus the function of a cell can often be predicted by the specific CD marker present. While it has been appreciated for many years that TH cells existed, it was unclear how helper cells worked until recent studies showed that soluble peptides secreted by activated TH could turn on selective portions of the immune response.
Initially, these glycoproteins produced by lymphocytes were called lymphokines. It is now known that many different cell types can produce these immune mediators. The current , more accurate term now used is cytokine. All cytokines have certain properties in common. They are all small molecular weight peptides or glycopeptides.
Each individual cytokine can have multiple functions depending upon the cell that produces it and the target cell s upon which it acts called pleiotropism.
Also, several different cytokines can have the same biologic function called redundancy. Cytokines can exert their effect through the bloodstream on distant target cells endocrine , on target cells adjacent to those that produce them paracrine or on the same cell that produces the cytokine autocrine. Their major functions appear to involve host defense or maintenance and repair of the blood elements Table 1. Cytokines are categorized by their major specific function s. There are four major categories of cytokines Table 2.badgepirates.burnsforce.com/11460.php
RNA Interference: New Therapeutics in Allergic Diseases | Bentham Science
Interferons are so named because they interfere with virus replication. There are three major types based upon the source of the interferon. Interferon alpha IFNa is produced by the buffy coat layer from white blood cells and is used in treatment of a variety of malignant and immune disorders. Interferon beta IFNb is produced by fibroblasts and is currently being evaluated in the treatment of multiple sclerosis.
Therapeutic Strategies towards Allergic Diseases
Interferon gamma IFNg is produced by activated T cells and is an important immunoregulatory molecule, particularly in allergic diseases. The colony stimulating factors are so named because they support the growth and differentiation of various elements of the bone marrow.
Other CSFs include Interleukin IL -3, which can stimulate a variety of hematopoietic precursors and is being evaluated as a therapy in aplastic anemia and bone marrow transplantation; and c-Kit ligand stem cell factor which has recently been demonstrated as a cytokine necessary to cause the differentiation of bone marrow stem cells into their various precursor elements for eventual differentiation into RBC, WBC and megakaryocytes platelets.
The tumor necrosis factors TNF are so called because injecting them into animals causes a hemorrhagic necrosis of their tumors. These molecules appear to be involved in the pathogenesis of septic shock and much research is aimed at trying to inhibit their activity in septic patients. Attempts have also been made to use the TNFs clinically to treat human tumors. Because of their extremely narrow therapeutic window efficacy vs toxicity , few view this as a useful stand-alone cancer therapy.
The largest group is the interleukins, so named because their fundamental function appears to be communication between inter- various populations of white blood cells leucocytes -leukin. Interleukins IL are given numbers.
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IL-4 causes a switch to IgE production by differentiating B cells. IFNg can inhibit that switch and prevent the production of specific IgE. Eosinophilic inflammation, a major component of allergic reactions, is under control of IL-5 and TNFa. Each of these events involve cellular recruitment to the reaction site called chemotaxis along with activation of these cells to produce their products and altered cellular traffic to gather the cells together in an optimal fashion to promote the allergic reaction. Remember, the host mistakenly believes this is a protective reaction. A group of proteins called adhesion molecules can be stimulated on both inflammatory cell surfaces as well as target cells i.
In addition, certain adhesion molecules likely have a role in inflammatory cell activation, further enhancing allergic inflammation. Environmental Allergens Thomas A. Platts-Mills Judith A. Woodfolk and Lisa M. Ontogeny of Allergy Bengt Bjorksten. Part II. Inflammation: Cellular Aspects. Inman Roma Sehmi Paul M. O'Byrne and Judah A. MacDonald Fiona L. Wills Tong-Jun Lin and A. Dean Befus. Human Langerhans Cells Thomas Bieber. Eosinophils Redwan Moqbel and Paige Lacy.
MacAry and David M. Airway Wall Structure Peter K. Jeffery Mariusz J. Gizycki and Andrew V.
Epithelium Mary H. Perdue and Derek M. Part III. Inflammation: Molecular Aspects. Signaling in Mast Cells Anthony P.