Allergies are a result of the immune system's hypersensitivity to compounds that are typically risk-free to the general populace.
Allergies. Image Credit: Elizaveta Galitckaia/Shutterstock.com
Though there are varying types of hypersensitivity the most prevalent is Type-1, which consists of an immediate (atopic, or anaphylactic) response. These are mediated by host antibodies that our leukocytes secrete. These antibodies (or immunoglobulins) associate with antigens- foreign substances from an external environment that provoke an immune response within the body.
Though 5 major classes/isotypes of immunoglobulin present themselves in our immune system, IgE immunoglobulin triggers most archetypical allergies, like those from eggs, soy, peanuts, shellfish, and so forth. In fact, within the last two decades, the frequency of IgE-mediated allergens has increased from 3% to 7% across the European Union and the United States.
The mechanism behind IgE immunoglobin-induced hypersensitivities.
IgE antibodies bind to Fcε receptors found on the surface of mast cells and basophils. When these IgE antibodies bind to their antigen counterparts, it cross-links to the Fcε receptor, which activates the mast and basophil cells. Activation consists of the discharge of chemical mediators, leading to the allergic response we see phenotypically. It is important to note, however, that this allergic response can only occur after re-exposure to the stimulus that produced the given IgE antibody response.
These IgE antibodies are synthesized from B cells, fashioned by two different signaling pathways. One incorporates the differentiation of Th cells into receptor Th1 or Th2 cells. Studies have concluded that for allergenic responses, the “Th2 helper cell” phenotype is preferred. While Th1 cells produce a reaction against bacterial and viral intracellular pathogens, Th2 cells mount a response against extracellular parasites. The later signaling pathway produces cytokines IL-4 & IL-13 stimulating the Th2 cells to convert to B cells.
Inappropriate Th2 responses are what lead to these allergies, and uncontrolled Th1 responses can even lead to different autoimmune diseases. To prevent this the bodies Th1 and Th2 cells naturally endeavor a cross-regulation of each other through cytokines. This means that the cytokines of one variant of T cell will repress the production of the other T cell variant and vice versa.
Investigative Research Into Allergenic responses.
Different labs have used molecular probes to differentiate Th2 cells to target different allergens such as alder pollen, peanuts, and other IgE mediated compounds. These immune cells were gathered from different people with allergies, and a positive correlation was found between the amount of Th2 cells found in a patient, and how many allergies that given patient has.
Even more interestingly, however, was the association between a lower Th2 cell count, and the capacity for a patient to become desensitized to peanut allergies.
Mass spectrometry has been used to profile the surface proteins of different Th1 and Th2 cells by ways of amino acid isotope labeling using the (SILAC) approach. It was found that the greatest discrepancy between the surface proteins of Th1 and Th2 cells were the amounts of BST2 (bonne marrow stromal protein 2) and TRIM (T cell receptor-interacting molecule). This implies that both TRIM and BST2 protein homologous are prime candidate targets to explore the regulation of Th1 and Th2 cells, given the role they play in maintaining our immune system.
Mechanisms of IgE-Antibody Therapeutics
This research led to the exploration of IgE-mediated mechanisms, caused by the regulation of Tropomyosin and arginine kinase within the body. Various retvertoses (ribose, arabinose, maltose) are used in these mechanisms. The sugar arabinose was found to reduce the sensitization of arginine kinase, implying that the same reduction could be done for Tropomyosin.
The Maillard reaction was employed in vivo to explore these hypoallergenic products. This mechanism employs the degradation of disulfide bonds and compromising the structural integrity of the Tropomyosin and arginine kinase. This is done in the secondary structural features of the protein, where “Maillard Tropomyosin” contained a greater number of β -turn and β -sheet structures than the wild type, and “Maillard arginine kinase” showed fewer α-helix structures.
These results bore fruit. The Malliard reaction fueled by arabinose can alter Tropomyosin arginine kinase to alter their structure. These modified epitopes can reduce the sensitization of a subject by oral ingestion. So far this has been for a control group of mice.
Alternatively, institutions such as the “American College of Allergy, Asthma & Immunology”, and the “Allergy Asthma Network” have followed serum-specific IgE’s, altering the catalyst itself rather than the substrate. This is being done now with different food samples, like soy, peanuts wheat, etc.
However, skin samples do not result in inconclusive results and could provide false positives even after someone has outgrown a food allergy. The sensitization for a given allergy has to be tested by eating the given food, which could lead to great complications if antigens in question cause a severe atopic, or anaphylactic response.
Though allergies pose a prominent threat to many people's immune systems, with close to 5% of the US population having suffered an episode of anaphylaxis, the fashioning of immunity to these allergens is still within its infancy. The role that Ige antibodies play with antigens must be explored further, and proper therapeutics are still within their infancy.
Though no concrete timetable has been made to mark the corrections to these allergenic reactions, researchers remain hopeful that allergies, in general, may one day be eliminated from the gene pool.
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