An allergic response in the human body begins upon first exposure
to the allergen. (National Institute of
Allergy and Infectious Diseases, 2013)
Upon the advent of the allergen, the immune system creates one type of antibodies,
known as specific immunoglobulin E, with specific affinity to that
substance. (Lerner, 2010; National
Institute of Allergy and Infectious Diseases, 2013. For a diagram of an antibody, see image 1.) A group of immunological molecules known as
interleukins promote the cloning of these IgE antibodies. (Robinson, 2013) During the second exposure, there is a much
larger immune response and elevated production flood the bloodstream with
allergen-specific IgE molecules.
(Robinson, 2013) These antibodies
move throughout the bloodstream and attach to the antigen binding cites of
specialized immune cells known as mast cells and basophils. (Urry, 2011; National
Institute of Allergy and Infectious Diseases, 2013; Urry, 2011) IgE levels are
typically very low in the bloodstream non-allergic person, but during an
allergic reaction, the body begins producing excessive amounts of the allergen
specific antibody. (de Weck, 2012;
Cohen, 2012) The IgE molecules do not
remain in the bloodstream for a long period of time. (Cohen, 2012) Instead, immediately after its
proliferation, the substance binds very strongly to the membrane of mast cells
in bodily tissue and blood basophils, both of which are unique types of immune
system inflammatory cells. (Tsai, 2012;
de Weck, 2012; National Institute of Allergy and Infectious Diseases,
2013) As inflammatory cells, both mast
cells and blood basophils contain “inflammatory mediators,” most commonly histamine
and serotonin. (de Weck, 2012) The strong binding of IgE molecules to the high-affinity
receptors of the inflammatory cells causes cross-linking between adjacent IgE
molecules. (Tsai, 2012; Cohen,
2012) This cross-linking triggers a
series of biochemical reactions and cascades within the mast cells that
eventually result in the cell’s “degranulation.” (Tsai, 2012) When the cell becomes “degranulated” its
membrane bursts and massive amount of granule-associated mediators are
released. (Parker, 2007; Tsai,
2012) These granule-associated
mediators, or inflammatory mediators, are liable for the majority of signs and
symptoms associated with allergic reactions.
(Tsai, 2012) The most common
granule-associated mediator in an allergic response is the molecule histamine, which
induces inflammation in various tissues, although a variety of other molecules
can be produced throughout the course of the reaction. (de Weck, 2012; Cohen,
2012) Histamine induces dilation and
increased permeability of small blood vessels in various body tissues and
constriction of the bronchi. (Robinson,
2013) These symptoms result in fluid
loss and swelling of the tissues.
(Robinson, 2013) For diagrams of
the cell response to IgE, see images 2-4.
Though the cause of food allergy is unknown, the disorder’s
effects on the body are well documented and well understood. (Staff, Mayo Clinic, 2011) The mast cells, primary proliferators of an
allergic reaction, are most common in the gastrointestinal tract, respiratory
tract, and skin. (Cohen, 2012) Therefore, it is unsurprising that these
areas are the most common sites of allergic reaction in the human body. (Cohen, 2012)
Though allergic symptoms vary widely between individuals, a handful of
them are common to most people who have food allergies. These include, itching of the mouth, swelling
of the lips and the tongue, symptoms that affect the gastrointestinal tract,
including vomiting, diarrhea, abdominal cramps, and abdominal pain, hives,
eczema and other skin issues, constricted throat or breathing, and a drop in
blood pressure. (National Institute of
Allergy and Infectious Diseases, 2013)
The inflammatory mediators released by the affected cells bring on these
archetypal symptoms. (Tsai, 2012) If the reaction is very severe, it can trigger
a response known as anaphylaxis. This
response is marked by an incredibly wide range of symptoms, most notably,
though, are swelling throughout the body tissues, wheezing, weak pulse, shock,
and fainting. (National Institute of
Allergy and Infectious Diseases, 2013) Such reactions are frightening,
unexpected, and have the potential to be deadly. Children and adults who live with this
condition have constant anxiety about anaphylaxis and other severe reactions
from ingestion and contamination. (Fleischer,
2013) Allergies are the single most
cause of days missed from school and work, and studies have shown that food
allergy has significant effects on the social activities, meal preparation, and
psychological state of children impacted by the condition. (Flesicher, 2013; Bollinger, 2010; Lerner,
2010) Though some children eventually
grow out of their allergies as they age, many do not, especially those with
peanut allergy. (Cohen, 2012; Fleicher,
2013)
Currently, there are no cures for food related allergies. (Fleischer, 2013) For many other types of allergy, subcutaneous
shots containing progressively higher amounts of the allergen have been shown
to desensitize the patient and often reduce allergy symptoms. (Fleischer, 2013) However, when trials of subcutaneous
injections were conducted on patients with peanut allergy, many individuals had
adverse reactions, and the practice was deemed unsafe. (Fleischer, 2013) At the moment, patients with food allergies
are advised to practice strict avoidance of the dangerous food. (Cohen, 2012)
This can be very difficult, and there is a high likelihood of possible
cross-contamination of foods in cafeterias and other public dining
facilities. If an individual’s food
allergies are very mild, his or her symptoms can be treated with drugs known as
antihistamines. (Staff, Mayo Clinic,
2011) These drugs negate the more mild effects
of histamine and reduce the symptoms of the condition. More severe allergic reactions and
anaphylactic reactions are treated with epinephrine injections and trips to the
emergency room. (Staff, Mayo Clinic,
2011) Epinephrine counteracts the symptoms
of high levels of histamine, increasing blood vessel diameter, reduces blood
vessel permeability, and relaxes the bronchi.
(Robinson, 2013) Yet, these
treatments are only temporary. They
treat the symptoms of allergies but they do not remedy the underlying intolerance
that causes the reaction.
For years, the means by which to remedy allergic intolerance has
eluded scientific researchers. There
have been no broadly available therapeutic options for allergy suffers, and
there have been myriad severe and fatal anaphylactic reactions brought on by
contact with food. (Fleischer, 2013) At
long last, however, there is hope for those who suffer from these allergies,
which comes in the form of oral and sublingual immunotherapy. Oral and sublingual immunotherapies, first
studied more than 100 years ago, have only recently come to the forefront of
scientific research. (Nowak-Wegrzyn,
2011) During oral and sublingual immunotherapy,
patients are administered small doses of the allergic food, either mixed into
other non-allergic foods or under the tongue in extract form,
respectively. (Nowak-Wegrzyn, 2011) The amount of allergens in these doses is
gradually increased over the course of many weeks, resulting in an elevated
tolerance to the substance in question. (Nowak-Wegrzyn, 2011) Patients
beginning treatment first establish the amount of allergen they can consume
without inducing a reaction. (Fleischer,
2013) After the initially dosage is
established, each individual begins a series of daily build-up doses, each
marginally greater than the last.
(Burks, 2012) Patients
periodically test their resistance to the allergen during “food challenges”
wherein an individual consumes incremental amounts of the substance in order to
determine his or her tolerance. (Fleischer, 2013) The dosages can continue as long as the
individual desires, or until an adverse reaction occurs. (Burks, 2012)
The immunotherapy trains the body, through repeated expose, to tolerate
what it had once rejected. (Fessenden,
2012)
Though oral and sublingual immunotherapy procedures are still in
trial phases, the results have been promising.
(Fleischer, 2013) Sublingual
immunotherapy treatment has been shown to raise tolerance in patients allergic
to kiwi, hazelnut, peach, milk, and, most recently, peanut. (Fleischer, 2013) In individuals allergic to peanut, the most
deadly known food allergy, sublingual immunotherapy raised tolerance from less
than two grams of peanut protein to over ten grams in some cases. (Fleischer, 2013) Tolerance increased greatly when therapy was
continued over many more weeks. (Fleischer,
2013) A similar study of oral
immunotherapy conducted with egg protein was even more successful, with 70% of
participants able to consume a cumulative dose of five grams of powder at ten
months of treatment. (Burks, 2012) Oral and sublingual immunotherapy show great
promise as food allergy treatment.
Measurements of the immune components of the subjects also revealed
encouraging results. In studies of the
peanut specific antibody levels in immunotherapy patients, trial participants
were found to have a decreased range of allergen-specific IgE molecules and
greater levels of polyclonal allergen-specific IgG4 serum. (Vickery, 2012; Burks, 2013; Fessenden,
2012) IgG4 is another
antibody, the serum of which is essential to the promotion of IgE in allergic reactions. (Vickery, 2012) There was also a decrease in peanut-specific interleukin
production; interleukins, which promote the propagation of IgE molecules, are
key to a strong allergic response.
(Blumchen, 2010; Robinson, 2013)
All of these biochemical signs correlate with a reduction or possible
discontinuation of allergic response. Furthermore,
the treatment was found to be incredibly safe.
(Hofmann, 2009) Very few
individuals had adverse reactions, and those reactions were always in the
hospital during build up days, where they could be safely treated. (Hofmann, 2009) Unlike subcutaneous
immunotherapy, which was discontinued because it was too dangerous for many
patients, oral and sublingual immunotherapy treatments seem to be safe, even
for those with serious peanut allergies.
(Blumchen, 2010; Hoffman, 2009)
Food allergy is a serious medical condition that affects
approximately 20% of Americans today.
(Lerner, 2010) For many years,
individuals with the condition have lived in fear of anaphylactic shock and
severe reaction. (National Institute of
Allergy and Infectious Diseases, 2013) A cure, other than symptomatic
treatment, has long evaded researches and medical practitioners. (Burks, 2012)
Recently, however, oral and sublingual immunotherapy have risen to
prominence. (Nowak-Wegryzn, 2011) By slowly increasing consumption of allergen,
these techniques increase body tolerance to the offending substance. (Fleischer, 2013) The treatment results in decreased diversity
of allergen specific IgE and increased levels of allergen specific IgG4,
both of which are good indicators of decreased allergic response. (Vickery, 2012) The treatment was found to be both safe and
very effective. (Hoffman, 2013;
Fleischer, 2013) It seems that the
future advancements for allergy suffers lie in the very substances to which
they are allergic. As oral and
sublingual immunotherapy gain prevalence and become widely used, one day we may
see a world without food allergy.
Appendix
Image 1
Image 2
 |
| This image gives a basic overview of the IgE propagation, binding, and subsequent histamine release in allergic tissue |
Lewis, Ricki. An Allergic Reaction - Overview.
McGraw-Hill Companies, Inc, Digital Image.
Nutri-Living, nd. Web. 25 Feb. 2013. <http://dft.ba/-allergicreaction>.
Image 3
 |
| This image shows the specific IgE molecules on an immune effector cell, and their cross-linking in the presence of an allergen. |
Nature Reviews. Allergen Activation and Cross-Linking of IgE
molecules. Digital image. Nature. Nature Reviews, n.d. Web. 25 Feb.
2013.
<http://www.nature.com/nrd/journal/v3/n7_supp/images/nrd1408-f1.jpg>.
Image 4
 |
| An image displaying the various paths of mast-cell activation. Note the presence of IgE and allergens, as well as the granule-associated mediators leading to inflammation of the tissue. |
Mast Cell Activation. Digital image. AccessScience.
McGraw-Hill Education, 2012. Web. 25 Feb. 2013. <http://www.accessscience.com/content/Mast%20cells/900114>.
Bibliography
Blumchen, Kathrina, Md,
Helen Ulbricht, Ute Staden, MD, Kerstin Dobberstein, John Beschorner, Lucila C.
L. De Oliveira, MD, Wayne G. Shreffler, MD, PhD, Hugh A. Sampson, MD, Bodo
Niggemann, MD, Ulrich Wahn, MD, and Kirsten Beyer, MD. "Oral Peanut
Immunotherapy in Children with Peanut Anaphylaxis." Journal of
Allergy and Clinical Immunology 126.1 (2010): 83-91. ScienceDirect.
Mosby, Inc., July 2010. Web. 25 Feb. 2013. <http://www.sciencedirect.com/science/article/pii/S0091674910007268>.
Bollinger, Mary E., DO,
Lynnda M. Dahlquist, PhD, Kim Mudd, RN, MSN, Claire Sonntag, BA, Lindsay
Dillinger, BA, and Kristine McKenna, MS. "The Impact of Food Allergy on
the Daily Activities of Children and Their Families." Annals of
Allergy, Astma, & Immunology 96.3 (2006): 415-21.ScienceDirect.
Elsevier Inc., 18 Feb. 2010. Web. 26 Feb. 2013.
<http://www.sciencedirect.com/science/article/pii/S1081120610609088>.
Burks, A. W., MD, Stacie M.
Jones, MD, Robert A. Wood, MD, David M. Fleischer, MD, Scott H. Sicherer, MD,
Robert W. Lindblad, MD, Donald Stablein, PhD, Alice K. Henning, MS, Brian P.
Vickery, MD, Andrew H. Liu, MD, Amy M. Scurlock, MD, Wayne G. Shreffler, MD,
PhD, Marshall Plaut, MD, and Hugh A. Sampson for the Consortium of Food Allergy
Research (CoFAR), MD. "Oral Immunotherapy for Treatment of Egg Allergy in
Children."The New England Journal of Medicine (2012):
233-43. The New England Journal of Medicine. Massachusetts Medical
Society, 19 July 2012. Web. 25 Feb. 2013.
<http://www.nejm.org/doi/full/10.1056/NEJMoa1200435>.
Cohen, John J. "Food
Allergy." AccessScience. McGraw-Hill Education, 2012. Web. 22
Feb. 2013.
<http://www.accessscience.com/content.aspx?searchStr=Food+Allergy&id=802770>.
De Weck, A. L.
"Allergy." AccessScience. McGraw-Hill Eductionation,
2012. Web. 23 Feb. 2013.
<http://www.accessscience.com/content/Allergy/024150>.
Fessenden, Marissa.
"The Exposure Cure." Scientific American 16 (2012):
307. Nature. Scientific American, 18 Sept. 2012. Web. 25 Feb. 2013.
<http://www.nature.com/scientificamerican/journal/v307/n4/full/scientificamerican1012-16.html>.
<http://www.nature.com/scientificamerican/journal/v307/n4/full/scientificamerican1012-16.html>.
Fleischer, David M., MD, A.
W. Burks, MD, Brian P. Vickery, MD, Amy M. Scurlock, MD, Robert A. Wood, MD,
Stacie M. Jones, MD, Scott H. Sicherer, MD, Andrew H. Liu, MD, Donald Stablein,
PhD, Alice K. Henning, MS, Lloyd Mayer, MD, Robert Lindblad, MD, Marshall
Plaut, MD, Hugh A. Sampson, MD, and Consortium of Food ALlergy Research
(CoFAR). "Sublingual Immunotherapy for Peanut Allergy: A Randomized,
Double-Blind, Placebo-Controlled Multicenter Trial." Journal of
Allergy and Clinical Immunology 131.1 (2013): 119-27. ScienceDirect.
Elsevier Properties S.A., Jan. 2013. Web. 24 Feb. 2013.
<http://www.sciencedirect.com/science/article/pii/S0091674912018246>.
Hine, Robert.
"Allergy." Science Online. Facts On File, Inc., n.d. Web.
25 Feb. 2013.
<http://www.fofweb.com/activelink2.asp?ItemID=WE40&SID=5&iPin=FDBF0094&SingleRecord=True>.
Hofman, Alison M., MD, Amy
M. Scurlock, MD, Stacie M. Jones, MD, Kricia P. Palmer, MD, Yuliua Lokhnygina,
PhD, Pamela H. Stelle, CPNP, Jamet Kamilaris, RN, and A. W. Burks, MD.
"Safety of a Peanut Oral Immunotherapy Protocol in Children with Peanut
Allergy." Journal of Allergy and Clinical Immunology 124.2
(2009): 286-91. ScienceDirect. Elsevier B.V., 27 May 2009. Web. 27
Feb. 2013.
<http://www.sciencedirect.com/science/article/pii/S0091674909005569>.
Lerner, K. L., and Brenda
W. Lerner. "Allergy." The Gale Encyclopedia of Science.
Gale Cengage Learning, 2010. Web. 25 Feb. 2013.
<http://ic.galegroup.com/ic/scic/ReferenceDetailsPage/ReferenceDetailsWindow?failOverType=&query=&prodId=SCIC&windowstate=normal&contentModules=&mode=view&displayGroupName=Reference&limiter=&currPage=&disableHighlighting=false&displayGroups=&sortBy=&source=&search_within_results=&action=e&catId=&activityType=&scanId=&documentId=GALE%7CCV2644030067>.
Mast Cell Activation. Digital image. AccessScience.
McGraw-Hill Education, 2012. Web. 25 Feb. 2013.
<http://www.accessscience.com/content/Mast%20cells/900114>.
National Institute of
Allergy and Infectious Diseases. "Food Allergy: An Overview." U.S.
Department of Health and Human Services, 2013. Web. 11 Jan. 2013.
<http://www.niaid.nih.gov/topics/foodallergy/documents/foodallergy.pdf>.
Nature Reviews. Allergen Activation
and Cross-Linking of IgE molecules. Digital image. Nature. Nature
Reviews, n.d. Web. 25 Feb. 2013.
<http://www.nature.com/nrd/journal/v3/n7_supp/images/nrd1408-f1.jpg>.
Nowak-Wegrzyn, Anna, MD,
and Hugh A. Sampsom, MD. "Future Therapies for Food Allergies." Journal
of Allergy and Clinical Immunology 127.3 (2011): 558-73. ScienceDirect.
Mosby, Inc., Mar. 2011. Web. 26 Feb. 2013.
<http://www.sciencedirect.com/science/article/pii/S0091674911000030>.
Parker, Steve.
"Allergies." The Human Body Book. 1st ed. New York: DK
Pub., 2007. 166. Print.
Robinson, Keith A.
"Biology 570 Immunology." Massachusetts, USA, Andover. 26 Feb. 2013.
Lecture.
Staff, Mayo Clinic.
"Food Allergy." Mayo Clinic. Mayo Foundation for Medical Education
and Research, 11 Feb. 2011. Web. 27 Jan. 2013.
Tsai, Mindy. "Mast
Cells." AccessScience. McGraw-Hill Education, 2012. Web. 23
Feb. 2013. <http://www.accessscience.com/content/Mast%20cells/900114>.
Urry, Lisa A., Michael L.
Cain, Steven A. Wasserman, Peter V. Minorsky, and Robert B. Jackson.
"Allergies." Campbell Biology AP Edition. By Jane B.
Reece. 9th ed. San Francisco: Pearson Benjamin Cummings, 2011. 947. Print.
Varsheney, Pooja, MD,
Stacie M. Jones, MD, Amy M. Scurlock, MD, Tamara T. Perry, MD, Alex Kemper, MD,
MPH, MS, Pamela Steele, CPNP, Anne Hiegel, RN, Jamet Kamilaris, RN, Suzanne
Carlisle, RN, Xiaohong Yue, MS, Mike Kulis, PhD, Laurent Pons, PhD, Brian
Vickery, MD, and A. W. Burks, MD. "A Randomized Controlled Study of Peanut
Oral Immunotherapy: Clinical Desensitization and Modulation of the Allergic
Response."Journal of Allergy and Clinical Immunology 127.3
(2011): 654-60. ScienceDirect. Mosby, Inc., Mar. 2011. Web. 25 Feb.
2013.
<http://www.sciencedirect.com/science/article/pii/S0091674911000509>.
Vickery, Brian P., MD, Jing
Lin, PhD, Micheal Kulis, PhD, Zhiyan Fu, PhD, Pamela H. Steele, MSN, CPNP,
Stacie M. Jones, MD, Amy M. Scurlock, MD, Gustavo Gimenez, BSc, Ludmilla Bardina,
MSc, Hugh A. Sampson, MD, and A. W. Burks, MD. "Peanut Oral Immunotherapy
Modifies IgE and IgG4 Responses to Major Peanut Allergens." Journal
of Allergy and Clinical Immunology 3rd ser. 131.1 (2013):
128-34. ScienceDirect. Mosby Inc., 27 Nov. 2012. Web. 11 Jan. 2013.
<http://www.sciencedirect.com/science/article/pii/S0091674912017721>.
