An allergen is both a foreign protein or semi-antigen (hapten) that induces the production of specific IgE antibodies and triggers an allergic reaction. Since the American physician Charles Harrison Blackley confirmed in 1873 that pollen is the real cause of chytridiomycosis, more and more allergens have been discovered (Table-1). The common allergens are mainly from dust mites, pollen, animal fur, drugs, food and insect venom. The most complex allergens are fungi, pollen and dust mites. The simplest allergens are animal hair. Not all proteins in allergens are allergenic, but depending on individual genetic susceptibility and the complexity of the allergen, numerous proteins can be recognized by sensitive individuals and trigger an allergic reaction. A single allergen that causes more than 50% of allergic patients to produce IgE is called the “major protein”.
The interaction of allergens and IgE underlies the development of allergic diseases such as allergic rhinoconjunctivitis, asthma, hyperreactive pneumonia, urticaria, eczema, contact dermatitis, atopic dermatitis, and angioedema. Most allergens are composed of proteins that have the same properties as common antigens, i.e., they stimulate the body to produce immunoglobulins such as IgG and IgM. At the same time, these allergens have specific biochemical and physicochemical properties that cause an overactive immune response in sensitive individuals, i.e., an allergic reaction. A large number of exogenous factors cause the immune system to recognize these proteins through altered host defense mechanisms. These factors include: genetic factors, industrial pollutants, smoking, viral infections, etc. The genetic characteristics of the host are important, and although the genes associated with allergic diseases are currently unknown, it is known that some pollen allergens such as American ragweed and ryegrass induce the production of IgE, which in turn is associated with the expression of major histocompatibility type I genes (HLA-A, -B, -C) and type II genes (HLA-DR, -DP, -DQ). The latter, in turn, is essential for the presentation of antigen fragments to helper T cells and the consequent production of antibodies.
Table 14-1 Allergens and their corresponding diseases
Asthma and/or allergic rhinitis
Allergic reactions (Anaphylaxis)
Atopic dermatitis
Grass pollen
Insect venom
Dust mites
Tree pollen
Drugs
Food allergens
Weed pollen
Food allergens
Occupational allergens
Fungi
Dust mites
Animal dander
Occupational allergens
Food allergens
I. Naming of allergens
The principle of allergen nomenclature was established by the Allergen Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS). Allergens are named according to the taxonomic name of their origin. This is done by using the first three letters of the genus name (separated by a space) and the first letter of the species name (separated by a space) and Arabic numerals. For example, the main antigen Der p 1 of Dermatophagoides pteronyssinus is composed of the first three letters of the genus name Der (space) + the first letter of the species name p (space) + the Arabic numeral 1. The number 1 represents the order in which the allergen was found or the clinical importance of the allergen.
Second, the type of allergens
(A) airborne allergens
1. Pollen
Pollen is the male reproductive cells of seed plants. Pollen is produced and released in the pollen sac. Some of them are spread by wind, some rely on insects, the former is called wind-borne flowers, the latter is called insect-borne flowers. Wind-borne flowers are characterized by their high yield, small size, light weight and, in some cases, air sacs, so they can be dispersed over great distances. Most of the pollen used as airborne allergens belongs to wind-borne flowers.
Different plants have different flowering periods, which creates a seasonal characteristic of pollen transmission. Botany divides the flowering time into three phases: the beginning of flowering, the peak of flowering, and the end of flowering. At the beginning of flowering, the first pollen starts to be dispersed; at the end of flowering, most of the flowers have withered and the number of pollen decreases sharply.
The dispersal of pollen in the air is also geographically specific. Although some pollen can be dispersed far away, generally pollen is dispersed mainly around the surrounding area of the flowering plant. The geographical distribution of plants due to different geographic conditions and anthropogenic reasons also contributes to the regional characteristics of pollen dispersal, which is of epidemiological importance in hay fever.
Pollen dispersal is also influenced by meteorological conditions. Generally speaking, high temperature and dry environmental conditions are most suitable for pollen dispersal. Conversely, lower temperatures and higher humidity are not conducive to pollen dispersal.
Pollen is the main source of airborne allergens, causing 10-20% of allergic diseases. It can be divided into three main categories: grass pollen, weed pollen and tree pollen. The allergenic components in pollen are mainly proteins. Different pollens have different protein components and their antigenicity is not consistent. Different pollens may have cross-reactivity with each other.
(1) Grass pollen: There are many types of grass pollen, and their allergens are also diverse. At present, based on the physicochemical and immunobiological properties of grass pollen allergens, they are divided into ten categories of allergens. These include expansins, extensins, ribonucleases, protease inhibitors-like proteins, calcium-binding proteins and profilins. (2) Weed pollen
(2) Weed pollen: The main weed pollen allergens closely related to allergic diseases are from the daisy family pollen, such as Artemisia, ragweed, sunflower and chamomile. In North America and Europe, the most studied allergen is ragweed allergen, whose main protein is pectate lyase, which is related to the cleavage of pectin. For pectin degradation, the involvement of many other enzymes is required, such as polygalacturonase, polymethylgalacturonase, and epimeric polygalacturonase lyase. These enzymes have also been shown to be present as allergenic components of tree pollen.
(3) Tree pollen: Depending on its source, tree pollen can be divided into angiosperm (flowering tree) pollen and gymnosperm (pine and cypress) pollen. A variety of allergens have been extracted from tree pollen. The most important allergens in angiosperm pollen are ribonucleases, whereas in gymnosperm pollen most of them are enzymes related to pectin degradation. These differences can be seen in the differences in the structure of the two types of pollen.
2. Fungi
Fungi (fungi) are a class of lower plants without the distinction of roots, stems and leaves, and belong to the phylum Fungi. Does not contain chlorophyll, so can not use inorganic material for photosynthesis, and can only camp parasitic or saprophytic life. Most fungi have mycelium and can reproduce sexually or asexually. The fungus is easy to grow in a warm and humid environment, so its distribution also has regional differences, more in coastal areas or inland humid areas, but other areas also have distribution. Different seasons, the distribution of the fungus is also different, generally more in summer and autumn, less in winter after snowfall. However, fungi can easily move indoors, thus becoming a perennial allergen. Allergenic fungi are mainly non-pathogenic fungi that are parasitic on decaying matter, but some fungi can both infect and allergenic to humans.
Fungi generally consist of spores and hyphae, both of which are antigenic, but spores are more antigenic and easily dispersed into the air, so fungal allergic reactions are mainly caused by fungal spores. The release of spores from different species of fungi is greatly influenced by external conditions. An extreme example is a fungus called Didymella exitialis, which releases spores only at night after rain. Allergenic fungi are mainly from Aspergillus, Mycosphaerella, Penicillium, Streptomyces, and Streptomyces. Among them, Aspergillus and Streptomyces play an important role in the development of asthma.
A large number of fungi are used in the manufacture of industrial enzymes, some of which may be potential allergens. Occupational fungal allergens are usually hydrolytic enzymes. And the allergen component of indoor fungi is often some enzymes related to glycolysis.
3. Dust mites
Dust mites belong to the phylum Arthropoda, class Arachnida, order True Mites, family Ixodes, genus Dust Mites. Only a few dust mites are associated with allergic reactions, mainly house dust mites (Dermatophagoides pteronyssinus), dust mites (Dermatophagoides farinae), dust mites (Euroglyphus maynei) and so on. The mites are divided into two parts: the carapace and the palpus. The adult carapace is oval in shape, about 350 μm long, with four pairs of legs. Females live for about 100-150 days, while males survive only 60-80 days. Water accounts for 81% of the mite’s body weight, and when the relative humidity drops to 50%, all dust mites die within 11 days, and house dust mites are even less able to tolerate dryness.
Human dander and grain dust are ideal feeders for mites, so mites exist in large numbers in bedding dust and grain dust. Mite carcasses, molts, and even excreta are antigenic. Clinical studies have proved that mites are important allergens causing allergic rhinitis and bronchial asthma.
4.Animal allergens
Allergens of animal origin are more common in the home and work environment. In the home environment, cats and dogs are common sources of allergens, while in some specific work environments rats, guinea pigs, horses and rabbits can also become important sources of allergens. The hair, epithelium, dander, urine, and saliva of these animals can be highly allergenic. Patients who are allergic to cats and dogs often show cross-sensitivity to different animal allergens. It is now recognized that albumin in serum can act as a relevant cross-reactive antigen.
(ii) Oral allergens
1. Food
Theoretically, any food has the potential to cause an allergic reaction. Common foods prone to allergic reactions are peanuts, nuts, seafood, mushrooms, milk, fruits, etc. The onset of food allergic reactions is complex, from type I to type IV allergic reactions are involved. The symptoms caused by food allergic reactions are also diverse, including gastrointestinal symptoms such as abdominal pain and diarrhea, skin symptoms such as urticaria, angioedema, eczema, and respiratory symptoms such as asthma and runny nose. The most important allergens in food include small clear proteins, promyoglobulin, actin, and lactic proteins. Some patients with pollen allergy can also have allergic reactions to fruits and vegetables at the same time. In particular, birch and grass pollens. In addition, common pollens that cross-react with food include beech pollen type 1 and type 2 allergens, whose components are ribonuclease and actin, respectively.
2. Drugs
Most of the drugs associated with allergic diseases have a small molecular weight and are generally present in the form of antigens. The representative drugs associated with allergic reactions in the rapid-onset phase are antibiotics and anesthetics, which can induce allergic reactions in small doses. Severe reactions such as anaphylaxis are usually associated with injectable medications.
(iii) Injectable allergens.
Exposure to allergens through the injectable route is also common. Most are caused by insect stings, but can also be caused by injectable medications. The main insects that can cause allergic reactions are bees, wasps, ants, and mosquitoes, of which bee venom is the most important type of allergen in this category, but it is not common to cause anaphylaxis. The venom of the above insects has a similar composition and contains mainly vasoactive amines, peptides, and several inflammatory enzymes such as phospholipase, hyaluronidase, and acid phosphatase.
Table 2 Common sources of allergens
Allergen types
Examples
Time of dispersal
Airborne allergens
Pollen
Grasses
Weeds
Trees
Ryegrass, wild oats, timothy, bermudagrass, duckweed
Artemisia, ragweed, plantain, big nettle, quinoa, grass
Birch, alder, cypress, hazel, beech, oak, hammock
Spring/early summer
Summer/autumn
Winter/spring
Mycorrhizal fungi
Aspergillus, Streptomyces, Mycosphaerella,
Perennial
Grain flour
Wheat, oats, rye
Perennial
Plant products
Rubber, papain, pineapple protease, lacquer
Perennial
Animal hair and urine
Cats, dogs, horses, rats, guinea pigs, rabbits, cows
Perennial
Bird feathers
Pigeons, chickens, ducks, parrots
Perennials
Dust mites
House dust mite, dust mite,
perennially
Oral allergens
Food
Seafood, nuts, flour, eggs, fruits, beans, sesame seeds, mushrooms, potatoes, coffee, chocolate, alcoholic beverages
No seasonality
Medications
Antibiotics such as penicillins, sulfonamides, etc., salazosulfapyridine, carbamazepine, etc.
No seasonality
Injected allergens
Insects
Bees, wasps and some hymenopterous insects such as mosquitoes
Summer
Drugs
Blood products, serums, vaccines, contrast agents, medications (including anti-asthmatic drugs and antibiotics)
No seasonality
Table 3 Pollens that cross-react with food allergens
Pollen
Food
Birch
Apple, cherry, radish, pear, peach, plum, fennel, potato, peanut, honey, celery, pecan, spinach, wheat, buckwheat
Artemisia absinthium
cherries, carrots, watermelon, chamomile, apples, hazelnuts
Grasses
Melon, tomato, orange, cherry
Wallflower genus
Cherry, melon
Ragweed
Melon, chamomile, honey, rubber, melon seeds
Pine
Pine cone
Hazelnut
Hazelnut