Editing Allergy (section)

==Cause==
Risk factors for allergies can be placed in two broad categories, namely [[Host (biology)|host]] and [[Natural environment|environmental]] factors.<ref name="The genetic and environmental basis of atopic diseases"/> Host factors include [[heredity]], sex, [[Race (classification of human beings)|race]], and age, with heredity being by far the most significant. However, there has been a recent increase in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to [[infectious disease]]s during early childhood, [[Pollution|environmental pollution]], allergen levels, and [[Diet (nutrition)|dietary]] changes.<ref name="Janeway"/>

===Dust mites===
{{main|Dust mite allergy}}

[[House dust mite|Dust mite]] allergy, also known as house dust allergy, is a [[Sensitization (immunology)|sensitization]] and allergic reaction to the droppings of [[house dust mite]]s. The allergy is common<ref>{{Cite news| vauthors = Alderman L |date=4 March 2011|title=Who Should Worry About Dust Mites (and Who Shouldn't)|language=en-US|work=The New York Times|url=https://www.nytimes.com/2011/03/05/health/05patient.html|access-date=23 July 2020|issn=0362-4331}}</ref><ref>{{Cite journal|title=Dust Mite Allergy|url=https://www.thh.nhs.uk/documents/_Patients/PatientLeaflets/paediatrics/allergies/PI018-Dust_Mite_Allergy_A4_May13.pdf|journal=NHS|access-date=27 July 2021|archive-date=26 April 2020|archive-url=https://web.archive.org/web/20200426125759/https://www.thh.nhs.uk/documents/_Patients/PatientLeaflets/paediatrics/allergies/PI018-Dust_Mite_Allergy_A4_May13.pdf|url-status=dead}}</ref> and can trigger allergic reactions such as asthma, [[Dermatitis|eczema]], or [[itch]]ing. The mite's gut contains potent digestive enzymes (notably [[Peptidase 1 (mite)|peptidase 1]]) that persist in their feces and are major inducers of allergic reactions such as [[Wheeze|wheezing]]. The mite's exoskeleton can also contribute to allergic reactions. Unlike [[scabies]] mites or skin follicle mites, house dust mites do not burrow under the skin and are not parasitic.<ref name="unl">{{cite web| vauthors = Ogg B |title=Managing House Dust Mites|url=https://lancaster.unl.edu/pest/resources/311dusmi.pdf|access-date=24 January 2019|publisher=Extension, Institute of Agriculture and Natural Resources, University of Nebraska–Lincoln}}</ref>

===Foods===
{{main|Food allergy}}
<!-- Foods by  preponderance -->A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow's milk, [[soy]], eggs, wheat, peanuts, [[tree nuts]], fish, and shellfish.<ref name="aafa.org">{{cite web |url= http://www.aafa.org/display.cfm?id=9&sub=20&cont=286 |title= Asthma and Allergy Foundation of America |access-date= 23 December 2012 |archive-url= https://web.archive.org/web/20121006052320/http://aafa.org/display.cfm?id=9&sub=20&cont=286 |archive-date= 6 October 2012 |df= dmy-all }}</ref> Other food allergies, affecting less than 1 person per 10,000 population, may be considered "rare".<ref name=Maleki/> The most common food allergy in the US population is a sensitivity to [[crustacea]].<ref name="Maleki">{{cite book | vauthors = Maleki SJ, Burks AW, Helm RM |title=Food Allergy |year=2006 |publisher=Blackwell Publishing |pages=39–41 |isbn=978-1-55581-375-8}}</ref> Although [[peanut allergies]] are notorious for their severity, peanut allergies are not the most common food allergy in adults or children. Severe or life-threatening reactions may be triggered by other allergens and are more common when combined with asthma.<ref name="aafa.org" />

<!-- Developmental differences; food allergies in children -->Rates of allergies differ between adults and children. Children can sometimes outgrow peanut allergies. [[Egg allergies]] affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.<ref>{{cite journal | vauthors = Järvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA | title = Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy | journal = Allergy | volume = 62 | issue = 7 | pages = 758–65 | date = July 2007 | pmid = 17573723 | doi = 10.1111/j.1398-9995.2007.01332.x | s2cid = 23540584 }}</ref> The sensitivity is usually to proteins in the [[Egg white|white]], rather than the [[yolk]].<ref name="Sicherer 63" />

<!-- Milk -->[[Milk allergy|Milk-protein allergies]]—distinct from [[lactose intolerance]]—are most common in children.<ref>{{harvnb|Maleki|Burks|Helm|2006|pp=41}}</ref> Approximately 60% of milk-protein reactions are [[immunoglobulin E]]–mediated, with the remaining usually attributable to [[proctocolitis|inflammation of the colon]].<ref>{{cite web |url=http://www.worldallergy.org/professional/allergic_diseases_center/foodallergy/ |title=World Allergy Organization |access-date=13 April 2015 |url-status=live |archive-url=https://web.archive.org/web/20150414054458/http://www.worldallergy.org/professional/allergic_diseases_center/foodallergy/ |archive-date=14 April 2015 }}</ref> Some people are unable to tolerate milk from goats or sheep as well as from cows, and many are also unable to tolerate dairy products such as cheese. Roughly 10% of children with a milk allergy will have a reaction to beef.<ref>Sicherer 64</ref> Lactose intolerance, a common reaction to milk, is not a form of allergy at all, but due to the absence of an [[enzyme]] in the [[digestive tract]].<ref name="m234">{{cite web | author=Cleveland Clinic medical professional | title=Lactose Intolerance | website=Cleveland Clinic | date=2023-03-03 | url=https://my.clevelandclinic.org/health/diseases/7317-lactose-intolerance | access-date=2024-06-29}}</ref>

<!-- Nuts -->Those with [[tree nut allergies]] may be allergic to one or many [[tree nuts]], including [[pecan]]s, [[pistachios]], and [[walnut]]s.<ref name="Sicherer 63" /> In addition, [[seeds]], including [[sesame seeds]] and [[poppy seed]]s, contain oils in which protein is present, which may elicit an allergic reaction.<ref name="Sicherer 63" />

<!-- Genetics and genetic engineering of foods -->Allergens can be transferred from one food to another through [[genetic engineering]]; however, genetic modification can also remove allergens. Little research has been done on the natural variation of allergen concentrations in unmodified crops.<ref>{{cite journal | vauthors = Herman EM | title = Genetically modified soybeans and food allergies | journal = Journal of Experimental Botany | volume = 54 | issue = 386 | pages = 1317–19 | date = May 2003 | pmid = 12709477 | doi = 10.1093/jxb/erg164 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Panda R, Ariyarathna H, Amnuaycheewa P, Tetteh A, Pramod SN, Taylor SL, Ballmer-Weber BK, Goodman RE | title = Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety | journal = Allergy | volume = 68 | issue = 2 | pages = 142–51 | date = February 2013 | pmid = 23205714 | doi = 10.1111/all.12076 | s2cid = 13814194 | url = https://digitalcommons.unl.edu/foodsciefacpub/165 | doi-access = free }}</ref>

===Latex===
[[Latex]] can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, 1 in 800 surgical patients (0.125 percent) reported latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins.<ref name="Sussman"/>

The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48–96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.<ref name=Sussman/> [[Anaphylactic]] reactions occur most often in sensitive patients who have been exposed to a surgeon's latex gloves during abdominal surgery, but other [[mucous membrane|mucosal]] exposures, such as dental procedures, can also produce systemic reactions.<ref name=Sussman/>

Latex and banana sensitivity may cross-react. Furthermore, those with latex allergy may also have sensitivities to [[avocado]], kiwifruit, and chestnut.<ref>{{cite journal | vauthors = Fernández de Corres L, Moneo I, Muñoz D, Bernaola G, Fernández E, Audicana M, Urrutia I | title = Sensitization from chestnuts and bananas in patients with urticaria and anaphylaxis from contact with latex | journal = Annals of Allergy | volume = 70 | issue = 1 | pages = 35–39 | date = January 1993 | pmid = 7678724 }}</ref> These people often have [[perioral]] itching and local [[urticaria]]. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, [[avocado]], [[kiwifruit]], and [[chestnut]] occurs because latex proteins are structurally [[Homology (biology)|homologous]] with some other plant proteins.<ref name=Sussman/>

===Medications===
{{main|Drug allergy}}
{{see also|Adverse drug reaction|Drug eruption}}
About 10% of people report that they are allergic to [[penicillin]]; however, of that 10%, 90% turn out not to be.<ref name=Al2015/> Serious allergies only occur in about 0.03%.<ref name=Al2015>{{cite journal | vauthors = Gonzalez-Estrada A, Radojicic C | title = Penicillin allergy: A practical guide for clinicians | journal = Cleveland Clinic Journal of Medicine | volume = 82 | issue = 5 | pages = 295–300 | date = May 2015 | pmid = 25973877 | doi = 10.3949/ccjm.82a.14111 | s2cid = 6717270 | doi-access = free }}</ref>

===Insect stings===
{{main|Insect sting allergy}}
One of the main sources of human allergies is insects. An allergy to insects can be brought on by bites, stings, ingestion, and inhalation.<ref name="f951">{{cite journal | last1=Fukutomi | first1=Yuma | last2=Kawakami | first2=Yuji | title=Respiratory sensitization to insect allergens: Species, components and clinical symptoms | journal=Allergology International | publisher=Elsevier BV | volume=70 | issue=3 | year=2021 | issn=1323-8930 | doi=10.1016/j.alit.2021.04.001 | pages=303–312| doi-access=free | pmid=33903033 }}</ref>

===Toxins interacting with proteins===
Another non-food protein reaction, [[urushiol-induced contact dermatitis]], originates after contact with [[poison ivy]], [[Toxicodendron pubescens|eastern poison oak]], [[Toxicodendron diversilobum|western poison oak]], or [[poison sumac]]. [[Urushiol]], which is not itself a protein, acts as a [[hapten]] and chemically reacts with, binds to, and changes the shape of [[integral membrane protein]]s on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a [[T-cell]]<nowiki>-</nowiki>mediated [[immune response]].<ref>{{cite web | vauthors = Hogan CM | url = http://globaltwitcher.auderis.se/artspec_information.asp?thingid=82914 | title = Western poison-oak: Toxicodendron diversilobum | archive-url = https://web.archive.org/web/20090721044257/http://globaltwitcher.auderis.se/artspec_information.asp?thingid=82914 | archive-date = 21 July 2009 | work = GlobalTwitcher | veditors = Stromberg N | date = 2008 | access-date = 30 April 2010 }}</ref>

Of these poisonous plants, sumac is the most virulent.<ref>{{cite book | vauthors = Keeler HL | date = 1900 | title = Our Native Trees and How to Identify Them | location = New York | publisher = Charles Scribner's Sons | pages = 94–96 }}</ref><ref>{{cite book | vauthors = Frankel E | title = Poison Ivy, Poison Oak, Poison Sumac and Their Relatives; Pistachios, Mangoes and Cashews | publisher = The Boxwood Press | location = Pacific Grove, CA | date = 1991 | isbn = 978-0-940168-18-3}}</ref> The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling, [[papule]]s, [[Vesicle (dermatology)|vesicles]], [[blister]]s, and streaking.<ref name="Dermatlas">{{DermAtlas|-1892628434}}</ref>

Estimates vary on the population fraction that will have an immune system response. Approximately 25% of the population will have a strong allergic response to urushiol. In general, approximately 80–90% of adults will develop a rash if they are exposed to {{cvt|0.0050|mg}} of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.<ref>{{cite journal |author1=Armstrong W.P. |author2=Epstein W.L. |title=Poison oak: more than just scratching the surface |journal=Herbalgram |volume=34 |pages=36–42 |year=1995 }} cited in {{cite web |url=http://waynesword.palomar.edu/ww0802.htm |title=Poison Oak |access-date=6 October 2015 |url-status=live |archive-url=https://web.archive.org/web/20151006212234/http://waynesword.palomar.edu/ww0802.htm |archive-date=6 October 2015 }}</ref>

===Genetics===
Allergic diseases are strongly [[Family|familial]]; [[Twin#Monozygotic twins|identical twins]] are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in [[Twin#Dizygotic twins|non-identical twins]].<ref name="Allergy"/> Allergic parents are more likely to have allergic children<ref name="DeSwert"/> and those children's allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent along [[Genealogy|genealogies]]; parents who are allergic to peanuts may have children who are allergic to [[ragweed]]. The likelihood of developing allergies is [[Heredity|inherited]] and related to an irregularity in the immune system, but the specific [[allergen]] is not.<ref name=DeSwert/>

The risk of allergic [[Sensitization (immunology)|sensitization]] and the development of allergies varies with age, with young children most at risk.<ref name="Croner"/> Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.<ref name=Croner/> The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.<ref>{{cite book |vauthors=Jarvis D, Burney P |chapter=Epidemiology of atopy and atopic disease | veditors = Kay AB |title=Allergy and allergic diseases |publisher=Blackwell Science |location=London |year=1997 |pages=1208–24 |volume=2 }}</ref>

[[Ethnic group|Ethnicity]] may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to [[human migration|migration]].<ref name=DeSwert/> It has been suggested that different [[Locus (genetics)|genetic loci]] are responsible for asthma, to be specific, in people of [[Caucasian race|European]], [[Hispanic]], [[Asian people|Asian]], and [[Ethnic groups of Africa|African]] origins.<ref name="African Americans with asthma: genetic insights"/>

Researchers have worked to characterize genes involved in inflammation and the maintenance of mucosal integrity. The identified genes associated with allergic disease severity, progression, and development primarily function in four areas: regulating inflammatory responses ([[IFN-α]], [[TLR-1]], [[Interleukin 13|IL-13]], [[Interleukin 4|IL-4]], IL-5, HLA-G, iNOS), maintaining vascular endothelium and mucosal lining (FLG, PLAUR, CTNNA3, PDCH1, COL29A1), mediating immune cell function (PHF11, H1R, HDC, TSLP, STAT6, RERE, PPP2R3C), and influencing susceptibility to allergic sensitization (e.g., ORMDL3, CHI3L1).<ref name="Frontiers">{{cite journal |last1=Falcon |first1=Robbi Miguel G. |last2=Caoili |first2=Salvador Eugenio C. |title=Immunologic, genetic, and ecological interplay of factors involved in allergic diseases |journal=Frontiers in Allergy |date=2023 |volume=4 |publisher=Frontiers|doi=10.3389/falgy.2023.1215616 |doi-access=free |pmid=37601647 |pmc=10435091 }}</ref>

Multiple studies have investigated the genetic profiles of individuals with predispositions to and experiences of allergic diseases, revealing a complex polygenic architecture. Specific genetic loci, such as MIIP, CXCR4, SCML4, CYP1B1, ICOS, and LINC00824, have been directly associated with allergic disorders.<ref name="Frontiers"/> Additionally, some loci show pleiotropic effects, linking them to both autoimmune and allergic conditions, including PRDM2, G3BP1, HBS1L, and POU2AF1.<ref name="Frontiers"/> These genes engage in shared inflammatory pathways across various epithelial tissues—such as the skin, esophagus, vagina, and lung—highlighting common genetic factors that contribute to the pathogenesis of asthma and other allergic diseases.<ref name="Frontiers"/>

In atopic patients, transcriptome studies have identified IL-13-related pathways as key for eosinophilic airway inflammation and remodeling. That causes the body to experience the type of airflow restriction of allergic asthma.<ref name="Frontiers"/> Expression of genes was quite variable: genes associated with inflammation were found almost exclusively in superficial airways, while genes related to airway remodeling were mainly present in endobronchial biopsy specimens.<ref name="Frontiers"/> This enhanced gene profile was similar across multiple sample sizes – nasal brushing, sputum, endobronchial brushing – demonstrating the importance of eosinophilic inflammation, mast cell degranulation and group 3 innate lymphoid cells in severe adult-onset asthma.<ref name="Frontiers"/> IL-13 is an immunoregulatory cytokine that is made mostly by activated [[T-helper 2 (Th2)]] cells.<ref name="U.S. National Library of Medicine">{{cite web |title=IL13 interleukin 13 [homo sapiens (human)] - gene |url=https://www.ncbi.nlm.nih.gov/gene/3596 |website=National Center for Biotechnology Information |publisher=U.S. National Library of Medicine}}</ref> It is an important cytokine for many steps in B-cell maturation and differentiation, since it increases CD23 and MHC class II molecules, and aids in B-cell isotype switching to IgE.<ref name="Frontiers"/><ref name="U.S. National Library of Medicine"/> IL-13 also suppresses macrophage function by reducing the release of pro-inflammatory cytokines and chemokines.<ref name="U.S. National Library of Medicine"/><ref>{{cite journal |last1=Zhu |first1=Chunhua |last2=Zhang |first2=Aihua |last3=Songming |first3=Huang |last4=Ding |first4=Guixia |last5=Pan |first5=Xiaoqin |last6=Chen |first6=Ronghua |title=Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-ΚB and c-jun N-terminal kinase in human mesangial cells |journal=Journal of Biomedical Research |date=2010 |volume=24 |issue=4 |pages=308–316 |publisher=U.S. National Library of Medicine|doi=10.1016/S1674-8301(10)60043-7 |pmid=23554645 |pmc=3596597 }}</ref> The more striking thing is that IL-13 is the prime mover in allergen-induced asthma via pathways that are independent of IgE and eosinophils.<ref name="U.S. National Library of Medicine"/>

===Hygiene hypothesis===
{{Main|Hygiene hypothesis}}
Allergic diseases are caused by inappropriate immunological responses to harmless [[antigens]] driven by a [[t helper cell|TH2]]-mediated immune response. Many bacteria and viruses elicit a [[T helper cell|TH1]]-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease.<ref>{{cite journal | vauthors = Folkerts G, Walzl G, Openshaw PJ | title = Do common childhood infections 'teach' the immune system not to be allergic? | journal = Immunology Today | volume = 21 | issue = 3 | pages = 118–20 | date = March 2000 | pmid = 10777250 | doi = 10.1016/S0167-5699(00)01582-6 }}</ref> In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens, and thus normally benign microbial objects—like pollen—will trigger an immune response.<ref>{{cite web |url=http://edwardwillett.com/2000/05/the-hygiene-hypothesis/ |title=The Hygiene Hypothesis |publisher=Edward Willett |date=30 January 2013 |access-date=30 May 2013 |url-status=live |archive-url=https://web.archive.org/web/20130430180522/http://edwardwillett.com/2000/05/the-hygiene-hypothesis/ |archive-date=30 April 2013 }}</ref>

The hygiene hypothesis was developed to explain the observation that [[hay fever]] and [[eczema]], both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child.<ref name="z256">{{cite journal | last1=Perkin | first1=Michael R | last2=Strachan | first2=David P | title=The hygiene hypothesis for allergy – conception and evolution | journal=Frontiers in Allergy | publisher=Frontiers Media SA | volume=3 | date=2022-11-24 | issn=2673-6101 | doi=10.3389/falgy.2022.1051368 | doi-access=free | page=| pmid=36506644 | pmc=9731379 }}</ref> It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries.<ref name="e520">{{cite journal | last=Bonis | first=Peter A. L. | title=Putting the Puzzle Together: Epidemiological and Clinical Clues in the Etiology of Eosinophilic Esophagitis | journal=Immunology and Allergy Clinics of North America | publisher=Elsevier BV | volume=29 | issue=1 | year=2009 | issn=0889-8561 | doi=10.1016/j.iac.2008.09.005 | pages=41–52| pmid=19141340 }}</ref> The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.<ref name="g732">{{cite journal | last1=Stiemsma | first1=Leah | last2=Reynolds | first2=Lisa | last3=Turvey | first3=Stuart | last4=Finlay | first4=Brett | title=The hygiene hypothesis: current perspectives and future therapies | journal=ImmunoTargets and Therapy | publisher=Informa UK Limited | year=2015 | volume=4 | pages=143–157 | issn=2253-1556 | doi=10.2147/itt.s61528 | doi-access=free | pmid=27471720 | pmc=4918254 }}</ref>

Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world, and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.<ref name="pmid12910582"/> Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.<ref name="pmid17326711"/> The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.<ref name="Antibiotic exposure during infancy"/> The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by [[caesarean section]] rather than vaginal birth.<ref name="A meta-analysis of the association between Caesarean section and childhood asthma"/><ref name="The use of household cleaning sprays and adult asthma: an international longitudinal study"/>

===Stress===
Chronic [[Stress (psychological)|stress]] can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of [[interleukin 12]] by both the [[autonomic nervous system]] and the [[hypothalamic–pituitary–adrenal axis]]. Stress management in highly susceptible individuals may improve symptoms.<ref>{{cite journal | vauthors = Dave ND, Xiang L, Rehm KE, Marshall GD | title = Stress and allergic diseases | journal = Immunology and Allergy Clinics of North America | volume = 31 | issue = 1 | pages = 55–68 | date = February 2011 | pmid = 21094923 | pmc = 3264048 | doi = 10.1016/j.iac.2010.09.009 }}</ref>

===Other environmental factors===
Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.<ref name=cooper04>{{cite journal | vauthors = Cooper PJ | title = Intestinal worms and human allergy | journal = Parasite Immunology | volume = 26 | issue = 11–12 | pages = 455–67 | year = 2004 | pmid = 15771681 | doi = 10.1111/j.0141-9838.2004.00728.x | s2cid = 23348293 }}</ref> Historically, the trees planted in urban areas were predominantly male to prevent litter from seeds and fruits, but the high ratio of male trees causes high pollen counts, a phenomenon that horticulturist Tom Ogren has called "[[botanical sexism]]".<ref>{{cite web | vauthors = Ogren TL |title=Botanical Sexism Cultivates Home-Grown Allergies |url=https://blogs.scientificamerican.com/guest-blog/botanical-sexism-cultivates-home-grown-allergies/ |website=[[Scientific American]] |date=29 April 2015 |access-date=18 January 2020}}</ref>

Alterations in exposure to [[microorganism]]s is another plausible explanation, at present, for the increase in [[Atopy|atopic allergy]].<ref name= Janeway/> Endotoxin exposure reduces release of inflammatory [[cytokine]]s such as [[tumor necrosis factor alpha|TNF-α]], [[interferon-gamma|IFNγ]], [[interleukin-10]], and [[interleukin-12]] from white blood cells ([[leukocytes]]) that circulate in the blood.<ref name="pmid12239255"/> Certain microbe-sensing [[protein]]s, known as [[Toll-like receptor]]s, found on the surface of cells in the body are also thought to be involved in these processes.<ref name="Epidemiological and immunological evidence for the hygiene hypothesis"/>

[[Parasitic worm]]s and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine [[Water chlorination|chlorination]] and purification of drinking water supplies.<ref name="Parasitic food-borne and water-borne zoonoses"/> Recent research has shown that some common parasites, such as intestinal worms (e.g., [[hookworm]]s), secrete chemicals into the gut wall (and, hence, the bloodstream) that [[immunosuppressant|suppress]] the immune system and prevent the body from attacking the parasite.<ref name="Worms and allergy"/> This gives rise to a new slant on the hygiene hypothesis theory—that [[co-evolution]] of humans and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive.<ref name=Yazdanbakhsh02>{{cite journal | vauthors = [[Maria Yazdanbakhsh|Yazdanbakhsh M]], Kremsner PG, van Ree R | title = Allergy, parasites, and the hygiene hypothesis | journal = Science | volume = 296 | issue = 5567 | pages = 490–94 | date = April 2002 | pmid = 11964470 | doi = 10.1126/science.296.5567.490 | bibcode = 2002Sci...296..490Y | citeseerx = 10.1.1.570.9502 }}</ref>

In particular, research suggests that allergies may coincide with the delayed establishment of [[gut flora]] in [[infant]]s.<ref name="pmid17382394" /> However, the research to support this theory is conflicting, with some studies performed in China and [[Ethiopia]] showing an increase in allergy in people infected with intestinal worms.<ref name="cooper04" /> Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.<ref name="falcone05">{{cite journal | vauthors = Falcone FH, Pritchard DI | title = Parasite role reversal: worms on trial | journal = Trends in Parasitology | volume = 21 | issue = 4 | pages = 157–60 | date = April 2005 | pmid = 15780835 | doi = 10.1016/j.pt.2005.02.002 }}</ref> It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected [[Mutualism (biology)|symbiosis]] is at work.<ref name="falcone05" /> For more information on this topic, see [[Helminthic therapy]].