ALLERGIES Allergies: Immune System Turned Extreme Why our Immune System Turns Against Us YOO JUNG KIM n allergy is generally described as molecules, cells, and organs that function antibodies speci"c to the allergen. (5) “an exaggerated immune response collectively to prevent illness, but not !e most obvious symptoms of allergies or reaction to substances that all instances of immune response are may include urticaria (hives), eczema Aare generally not harmful” (1). !ese bene"cial. In certain cases, the immune (rashes), conjunctivitis (in%ammation substances can include pollens, speci"c system can react excessively to a potential of the eyelids), and asthma. As the name foods, dusts, molds, latex, and insect stings threat, leading to continuous acute or “immediate hypersensitivity” suggests, this (1, 2, 3). To those who su#er from allergies, systematic cellular damage known as reaction occurs rapidly, usually "&een to the consequences of consuming the wrong hypersensitivity (5). twenty minutes from the time of exposure food or being stung by the wrong insect to the antigen. !e initial symptoms may can range from being uncomfortable to Overview of Hypersensitivity be followed by a second, delayed onset of life threatening. Symptoms could be as symptoms a&er ten to twelve hours (7). In the 1960s, two British mild as itchiness to as extreme as breathing Biologically, Type I Hypersensitivity immunologists, Robin Coombs and di$culties, vomiting, and death (4). reactions are mediated by a speci"c class of Philip Gell created a classi"cation system antibody called Immunoglobulin E (IgE). for sorting undesirable immunological Overview of the Immune In a normal immune response, IgE protects reactions into four categories, which were against large pathogens such as helminthes Syst em classi"ed by the “principal immunologic and protozoans by binding to IgE-speci"c mechanism” and the time required for !e immune system protects an receptors called FcεRI, located on mast cells, adverse reactions to occur. In 1963, Gell organism from a wide spectrum of foreign basophils, lymphocytes, and monocytes. and Coombs published their "ndings in pathogens, a feat requiring a tremendous Upon binding of IgE, these cells cause the “Clinical Aspects of Immunology,” which degree of %exibility. In particular, the release of biochemical mediators, such as soon became the authoritative textbook mammalian immune system is composed histamine, prostaglandin, slow-reacting on medical immunology, running to "ve of three physiological components: the substance of anaphylaxis (SRS-A), and editions in thirty years (6). external barriers, the innate immune leukotrienes, which can cause contractions One of the adverse immune system, and the adaptive immune system. of smooth muscle, increased vascular responses noted by Gell and Coombs External barriers—the "rst level permeability, and increased mucous was hypersensitivity. Hypersensitivity is of protection against pathogens—are secretion. !e sum of these reactions may a condition in which immune responses composed primarily of physical obstacles, lead to “anaphylaxic shock,” a potentially target self-antigens, which result from such as epithelial cells, and chemical deadly type of whole-body hypersensitivity uncontrolled, excessive, or inappropriate barriers such as sweat, tears, or saliva, all of reaction that includes dilation of blood responses against foreign antigens, such as which contain anti-microbial compounds vessels, massive edema, hypotention, and microbes and allergens. All hypersensitivity (5). If a pathogen can successfully breach cardiovascular collapse. (5, 8) reactions require a pre-sensitized (immune) this "rst level of defense, it must then While a speci"c allergy cannot be state of the hosts. Allergies—under Gell face components of the innate immune inherited, one’s predisposition to allergic and Coomb’s classi"cation—fall under system: a host of non-speci"c mechanisms disease is di#erentially correlated with Hypersentitivity Type I, also known as such as phagocytic cells (neutrophils, genetic factors. If one parent has any type immediate or anaphylactic hypersensitivity macrophages), natural killer cells, the of an allergy, “chances are 1 in 3 that each (5). complement system, and cytokines, all of child will have an allergy. If both parents which can act to eliminate a diverse array of pathogens and infections. Adaptive Biological Mechanisms of immunity is mediated by lymphocytes Allergy (B cells and T cells ) and is stimulated by All hypersensitivity reactions, exposure to infectious agents. In contrast including allergies, require prior to innate immunity, adaptive immunity sensitization and memory, processes that is characterized by speci"city for distinct involve components of the innate and macromolecules. A striking feature of the adaptive immune system. During the initial adaptive immune system is its “memory,” exposure, would-be allergens are captured, which enables the immune system to processed, and presented by antigen- respond with greater vigor to future presenting cells (APCs) to activate allergen- exposures to the same pathogen (5). speci"c T-helper cells. !ese cells then Both the innate and adaptive systems Image courtesy of Wolfgang Ihloff retrieved from http://commons.wikimedia.org/wiki/ enable B cells to di#erentiate and produce File:Allergy_skin_testing.JPG (accessed 10 May 2012) are composed of a vast spectrum of Figure 1: Allergy skin testing. 24 DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE Conclusion Our understanding of the biological pathways of allergic diseases continues to grow, but some of the most important questions have yet to be answered. While several hypotheses regarding the origin of allergies have been raised, scientists have yet to reach a consensus on the evolutionary persistence of allergies (12). Furthermore, despite several conjectures, the steadfast increase in rates of allergic disease in industrialized countries remains largely unexplained (12). While commonplace, allergies can present a signi"cant detriment to the overall lifestyle of individuals. !e increase in cases of allergies in virtually all American demographics raises social, environmental, and public health concerns. Researchers Image courtesy of SariSabban retrieved from http://en.wikipedia.org/wiki/File:The_Allergy_Pathway.jpg (accessed 10 May 2012) Figure 2: Simplified diagram showing key events that leads to allergy initiation. from a vast spectrum of "elds must work in tandem to address the prevalence of have allergies, it is much more likely (7 in In potentially life-threatening allergic allergic diseases in industrialized countries. 10) that their children will have allergies” reactions, epinephrine can be injected to (3). relax the muscles in the airways and reduce #/.4!#49//*5.'+)-!49//*5.' Allergy Testing and Treatment the tightening of the blood vessels, thereby +)- $!24-/54(%$5 preventing asphyxiation (10). !e most prevalent method of testing References for allergies is through the skin, otherwise Social and Environmental 1. Environmental Protection Agency Research & known as the prick test. To observe for the Development (February 2011). Available at http:// presence of allergies, a medical provider Trends in Allergy www.epa.gov/ord/gems/scinews_aeroallergens.htm. can place minute doses of the suspected !e prevalence of allergies has reached (April 2012). allergen samples under the skin. A&er few 2. Allergies. PubMed Health (2011). Available pandemic levels in industrialized counties. at http://www.ncbi.nlm.nih.gov/pubmedhealth/ minutes , the skin is then observed for In America, total cases of allergies have PMH0001815/. (April 2012). symptoms of in%ammation (3). increased since the 1980s in virtually all 3. Allergy Facts and Figures. Asthma and Allergy While there is no known cure for demographics, becoming one of the most Foundation of America. Available at http://www.aafa. allergies, current over-the-counter and org/display.cfm?id=9&sub=30. (April 2012) common chronic medical conditions 4. C. Hadley, EMBO reports 7, 1080 – 1083 (2006). prescription medication can inhibit in America (11). !e costs accrued by 5. A. Abbas, Basic Immunology: Functions and production or release of in%ammatory treatment for airborne allergens such as Disorders of the Immune System (Saunders Elsevier, mediators which cause symptoms most dust and pollen total $21 billion annually New York, ed. 3, 2011), [third edition]. commonly associated with allergies. 6. D. H. Pamphilon, British J. of Haematology. 137, in the United States (3). 401-208 (2007). !ese include non-steroidal anti- Researchers have postulated a 7. A. Gha#ar, University of South Carolina School of in%ammatory drugs (NSAID) such as correlation between the longevity and Medicine (2010). Available at http://pathmicro.med. aspirin, indomethicin, and synthetic severity of allergic symptoms and climate sc.edu/gha#ar/hyper00.htm. (April 2012). steroids such as glucocorticoids. Other 8. A.D.A.M. Medical Encyclopedia. PubMed Health change. Systemic increases in temperature, (2010). Available at http://www.ncbi.nlm.nih.gov/ potent drugs include those that inhibit carbon dioxide levels, and precipitation pubmedhealth/PMH0001847/. (April 2012). mediator action such as histamine receptor have enabled the growth of various species 9. Allergy Shots. WebMD. Available at http://www. antagonists (antihistamines) like Benadryl of plants known to cause and exacerbate webmd.com/allergies/guide/shots. (April 2012). and Dramamine, both of which prevent