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Haiyaa, why no peanuts? Why so weak?



An iconic line by Malaysia’s own Uncle Roger whenever someone rejects peanuts due to allergies. Most of us will know that an allergy is not to be taken lightly due to the risks it carries. However, have you ever stopped to wonder, why though? How can something as harmless as peanuts cause someone to go into life-threatening situations? Especially in the current season of spring, it might be blasphemous to even ponder upon the fact that pollen can cause ICU admissions. Fret not, this article will introduce you guys to the physiology behind allergies, and how our immune system can really mess stuff up.



Why are we discussing this topic?


First and foremost, what is an allergy and why is it important? In brief, an allergy is an exaggerated immune response to certain foreign substances that can lead to a wide range of side effects, ranging for mild irritation to anaphylaxis, a potentially life threatening condition that includes nausea, difficulty breathing, vomiting, extremely low blood pressure, and if untreated death (Mayo Clinic, 2018). Contrary to popular belief, allergies affect adults and children alike, with the CDC reporting more than one quarter of adults and 1 in 5 children having seasonal allergies, as well as 6% of adults and children having food allergies (CDC, 2023).


Figure 1: CDC Statistics for Allergies


Fun stuff


With that out of the way, let’s dive into the intricacies of what makes an allergy so dangerous. Our immune system is normally there to help keep us safe from harmful substances such as bacteria, viruses, and other microorganisms. The immune system is composed of many different cell types such as macrophages, lymphocytes, mast cells, and many more. Usually, when these cells detect something foreign in the body, they secrete specific substances to initiate inflammation and to prevent the pathogens from harming the body. Allergic reactions begin in the immune system when harmless substances such as dust, pollen, or food substances are recognized by these cells and trigger an immune response (John Hopkins Medicine, 2019).


There are many different types of allergies, but the most common ones are IgE-mediated, which is what we will discuss mostly here (Dougherty, Alsayouri and Sadowski, 2020). During the first exposure to an allergen, dendritic cells and macrophages gobble up the allergen and present them to a T-helper cell. The T-helper cells then scours the body to present this allergen to B-cells that have a specific receptor for the allergen. Once this match has been found, the B-cells rapidly multiply and produce IgE antibodies specific to the allergen. These antibodies bind onto mast cells and basophils, which are another type of immune cells. This phase is usually called the sensitization phase (Charles A Janeway et al., 2001). 


Figure 2: Development of immunological memory to allergens. Image taken from FutureLearn.


During the next exposure, these allergens bind to the IgE antibodies and cause the mast cells and basophils to degranulate and release the contents in it. The contents include histamine, and prostaglandins which cause systemic inflammation. Normally, these molecules help dilate blood vessels, and recruit immune cells to the rescue. However, during allergic reactions, the release of these molecules is excessive and causes too much vasodilation, which can result in low blood pressure. Besides, it can also cause excessive mucus secretion, stimulation of sensory nerves, and smooth muscle spasms. This can cause someone to enter a state of anaphylactic shock, with symptoms such as hypotension, difficulty breathing, dizziness, nausea, an abnormal heart rate, and loss of consciousness  (Dougherty, Alsayouri and Sadowski, 2020).


Figure 3: Symptoms of anaphylactic shock. Image taken from Cleveland Clinic.


Besides these acute phase responses, late-phase response can also bring harm to the patients. The late phase response is a result of induced synthesis and release of mediators including leukotrienes, chemokines, and cytokines from the activated mast cells. These recruit other immune cells, including eosinophils to the site of inflammation. The late-phase response can cause sustained edema, and can convert into a chronic inflammatory response as in the case of chronic asthma. This chronic state of inflammation then further stimulates eosinophilia and further IgE production in a vicious cycle (Charles A Janeway et al., 2001).


How do I know if I have allergies?


To assess the presence of allergen-specific IgE antibodies, a skin prick test, and an allergy blood test is used. A note to point is that allergy undergoes dynamic changes over time, hence regular testing is important to provide information on patient management. Annual testing is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown, and the testing interval is extended to 2–3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish (NIAID-Sponsored Expert Panel, 2010).


Skin prick testing involves injecting tiny amounts of suspected allergens on sites of a skin marked with pen or dye. A negative control, glycerin, and a positive control, histamine is also included for comparison. The injection site usually is the forearm or back. If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blown hive in more sensitive patients similar to a mosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/− meaning borderline reactivity, and 4+ being a large reaction (Mayo Clinic, 2022).


Figure 4: Skin testing on back. Image taken from Wikipedia.


Blood testing on the other hand is much more simple and involves measuring the concentration of specific IgE antibodies in the blood sample sent in by a patient. In general, a high allergen-specific IgE antibodies value predicts great likelihood of symptoms, however not having or having a low allergen-specific IgE antibodies does not rule out being allergic to that substance as the immune system may just not yet be sensitized yet (Yunginger et al., 2000).


How are allergies managed


The most common management procedure for allergies are simply just to avoid anything that can trigger an allergic response. However, this may not always be feasible. Those with allergies often carry around something known as an Epi-pen, which is used to inject epinephrine into the body. Epinephrine binds onto adrenergic receptors mainly in the airway smooth muscles, and the smooth muscles around our blood vessels. This reverses the effects of the various secreted molecules during an allergic reaction and can really be a life-saving intervention. Other medications that have the same reversing capabilities include antihistamines, glucocorticoids, and antileukotriene agents (Mayo Clinic Staff, 2017).


Figure 5: EpiPen, a common allergy medication. Image taken from epipen.ca.


These however are more acute forms of treatment and does not stop the body from overreacting to the allergens. Allergen immunotherapy involves gradually exposing people to larger and larger amounts of allergen to “teach” the immune system to change its response. Meta-analyses have found that subcutaneous injections of allergens is effective in treatment of allergic rhinitis (Penagos et al., 2006), especially in children who have immune systems that are more prone to change, and in asthma (Abramson, Puy and Weiner, 2010). What’s even better is that the benefits may last for years. Allergen immunotherapy is mostly done for environmental allergies, but more recently oral allergen immunotherapy has been gaining more evidence in favor of it helping reduce food allergies (Muraro, Tropeano and Giovannini, 2022).


Conclusion

In conclusion, the most important thing to acknowledge (if you don’t already know), is that having allergies does not mean you’re weak (contrary to what Uncle Roger says). It is the result of a faulty immune system that overreacts to harmless particles, and is not something we can control to a high degree actively. With that being said, understanding what is actually happening behind the scenes may empower those suffering with allergies and enable medical advancements to help reduce the burden these people face.

 

Article prepared by: Jared Ong Kang Jie, MBIOS R&D Director 23/24


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References


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  2. CDC (2023). More Than a Quarter of U.S. Adults and Children Have at Least One Allergy. [online] www.cdc.gov. Available at: https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220126.htm. 

  3. Charles A Janeway, J., Travers, P., Walport, M. and Shlomchik, M.J. (2001). Effector mechanisms in allergic reactions. Immunobiology: The Immune System in Health and Disease. 5th edition. [online] Available at: https://www.ncbi.nlm.nih.gov/books/NBK27112/. 

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  5. John Hopkins Medicine (2019). Allergies and the Immune System. [online] John Hopkins Medicine. Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/allergies-and-the-immune-system. 

  6. Mayo Clinic (2018). Allergies - Symptoms and causes. [online] Mayo Clinic. Available at: https://www.mayoclinic.org/diseases-conditions/allergies/symptoms-causes/syc-20351497. 

  7. Mayo Clinic (2022). Allergy skin tests - Mayo Clinic. [online] www.mayoclinic.org. Available at: https://www.mayoclinic.org/tests-procedures/allergy-tests/about/pac-20392895. 

  8. Mayo Clinic Staff (2017). Allergy medications: Know your options. [online] Mayo Clinic. Available at: https://www.mayoclinic.org/diseases-conditions/allergies/in-depth/allergy-medications/art-20047403. 

  9. Muraro, A., Tropeano, A. and Giovannini, M. (2022). Allergen immunotherapy for food allergy: Evidence and outlook. Allergologie select, 6(01), pp.285–292. doi:https://doi.org/10.5414/alx02319e. 

  10. NIAID-Sponsored Expert Panel (2010). Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. Journal of Allergy and Clinical Immunology, [online] 126(6), pp.S1–S58. doi:https://doi.org/10.1016/j.jaci.2010.10.007. 

  11. Penagos, M., Compalati, E., Tarantini, F., Baena-Cagnani, R., Huerta, J., Passalacqua, G. and Canonica, G.W. (2006). Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Annals of Allergy, Asthma & Immunology, 97(2), pp.141–148. doi:https://doi.org/10.1016/s1081-1206(10)60004-x. 

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