Allergens and Allergenic Preparations

Allergy

• Allergy is define as “the abnormal or unusual response to a substance by human body is called allergy. OR

• The harmful reaction to the external substances is known as allergy.

• The external substances are known as allergens.

History

• Allergy has been a medical specialty more than 50 years, although symptoms of allergy has been recognized for many years.

• The term Allergy was defined in 1906 by Von Pirquet in describing a change or altered reaction the body. When an individual develops and unusual response to substance or conditions that is harmless to other. The individual is said to be allergic.

The first reference to allergic disease was found in the papyrus Ebers in which asthma and diseases owing to “autointoxication” where maintained. The writing of Hippocrates record the least 12 records of asthma, the first case of Hayfever symptoms was recorded by Herodotus.

Cause of Allergy

• According to published figure half of the U.S.A population suffering from sort of allergic syndrome. The exact cause of the allergy is still un determined. The reasons why an individual exhibit allergic response to regweed pollen and other do not understood.

• Based on genetic study, medical immunological investigators generally agreed that the tendency to be allergic is hereditary.

• In addition to it various other factors such as emotional factors , atmospheric factors, psychosomatic factors and chronic types of infection. However, because the most allergens are composed of plant or animal matters, they merit consideration in a treatise on natural products.

Predisposing Factors

• Predisposing factors that make some persons susceptible to allergy are:

• Hereditary tendency to allergic response. • Dysfunction of the endocrine glands. • Increased excitability of sympathetic and parasympathetic

nervous systems• Absorption of toxic metabolic and catabolic substances. • Hepatic dysfunction• Psychic influences.• Types of symptoms depend on the shock organ affected by

particular allergens and its path of entry to the body.

Allergens

• These are antigenic substances capable of sensitizing the body in such a way that unusual responses occur in the hypersensitivity individuals. Almost any substances weather of biological, chemical or synthetic origin, may prove to be allergens.

• The allergen concerned with the patients symptoms must be antigenic; that must be capable of eliciting an antibody response. The antibodies are special protein molecule helps to neutralize the parasitic invaders and protect the person from further exposure. If immune system is not strong disease condition occur. The reaction between antigen and antibody is called antigen-antibody reactions. Some of allergens circulate in the blood and other which become attached to the cells of the nasal membranes (fixed antibodies), which may either inhaled, eaten, injected or contacted to the skin.

Types of Allergic reactions

• Allergic reactions may be of two types • A. Localized reactions: If the state of shock is

confined to the area of the introduction of the allergen, the condition is a localized reaction.

• e.g. when pollen grains are inhaled which cause sinusitis due to allergic reactions. The sinusitis is restricted to the face so allergic reactions are localized.

Generalized reactions:

• If it is extended beyond this area it may be generalized or constitutional reactions.

• The constitutional reactions are produce in the some patients by the injection of penicillin preparations and extremely uncomfortable and sometime dangerous and even fatal.

Mechanism of action of allergens

• Generally allergic reactions takes place in following steps

• Primary Exposure • Secondary Exposure & Release of mediators

Primary Exposure:

• When the body is first subjected to the allergen (antigen), the condition is referred to as primary exposure. Because no antibodies has been formed previously, no symptoms of the allergy are produced during the primary exposure.

Secondary Exposure and release of mediators

• However during the subsequent exposure, the allergen contacts the antigen-antibody reactions.

• During secondary expose the antibody become attach to the mast cells-white blood cells (basophils), and form a complex and as a result basophils burst due to antigen-antibody reaction causes a liberation of histamine, bradykinin and other mediators of allergic symptoms.

Types of Allergens

• Inhalant Allergens: substances that are distributed in the atmosphere and contact the nasal or buccal mucosa during respiration are called inhalant allergens.

• Ingestant Allergens: Those that occur in the foodstuff and are swallowed are known as ingestant.

• Injectants Allergens: Those may be present in the solutions intended for parenteral administration are known as injectants.

• Contants Allergens: Those that come in direct contact with epithelium.

• Infectants Allergens: metabolic wastes and growth products of pahtogenic microorganisms.

• Infestants Allergens: Parasitic microorganisms in or on the body.

• In addition to these materials allergy may be caused by heat, cold, changes in climit, anger or frustration (psychosomatic allergy) and others.

Inhalant Allergens

• Inhalant Allergens: substances that are distributed in the atmosphere and contact the nasal or buccal mucosa during respiration are called inhalant allergens.

Allergic symptoms

• Repetitive sneezing, release of watery fluids, swelling of nose, itching redness and lacrimation of eyes.

• The allergic reactions are localized because the symptoms are restricted to face only. Similar symptoms may appear in case of ingestant allergy.

condition

• The allergic condition or condition of the body is known as sinusitis (inflammation of sinuses or nasal passage) or hayfever.

• Types of Hayfever:• Seasonal Hayfever or pollinosis • Non-seasonal Hayfever or perennial rhinitis

• SEASONAL HAYFEVER: the allergic symptoms may be develop during certain season (months) of the year. This condition is also known as pollinosis because it is related with the release of pollen grains from certain plants.

• Types of seasons on the basis of pollen grains• There are three pollen seasons

• The tree season, in spring which extends from feb. to june.

• The grasses season, after spring or early summer from april to Aug.

• The ragweed season in late summer from Aug. to mid Oct.

Thus the season in which allergic symptoms occur can be identified the types of pollens grains responsible for the allergy.

Composition of Pollen Grains

• Pollen grains can be distinguished and identified easily due to their heterogeneous nature.

• They may be oval, round, annular, square or rectangular in shape. The outer surface of pollen grains is called “exine” while the inner surface is “intine”. Due to shape and surface appearance of exine, the type of specific pollen grains may be identified.

The pollen grains may be spread through wind or insects. So the pollens liberated through the anemophilous plants are called atmospheric pollens. These are wind pollinated pollens e.g. pollens of tree such as oak and walnut, pollens of grasses bermuda and timothy, pollens of weeds such as ragweed and plantain.

The pollens liberated through entomophilous plants (insects pollinated) are called insect pollinated pollens e.g. pollens of clover, hollyhock and honeysuckle etc.

Non-seasonal Hayfever

• In case of non seasonal hay fever the allergic symptoms may be developed through out the year with out regularity. It is caused by inhalant allergens other than pollen grains like fungus spore, dust etc. it is also called perennial rhinitis

• The condition may be for a few days, then disappear and reaper after few days or month or some time it is not regular.

Causes of Non-seasonal Hay fever

• It is due to inhalant allergens at the place of living or work. These allergens are:

• Cotton pillow cases: in home cotton may cause allergy to hypersensitive person.

• Odor and perfumes: cosmetics contain volatile oils which are inhaled and cause Hay fever.

• Animal Epidermis or Dander: the epithelial scales called dandra of pet animals (cats, dogs) also cause allergy or Hay fever.

• Castor beans: the castor oil seeds contains allergens in the oil cake which cause severe allergy to the person in industry (use castor beans).

• Fungus spores: the spores are produce by the fungi and distribute in air and cause allergy when inhaled.

• Dust: it is mixture of different pollens, mold spores, cotton, animal dander, and several other substances. All these substances produce non-seasonal Hay fever.

• The test for dust allergy is difficult then other tests of allergy.

Ingestant Allergens

• Substances that are found in foods stuffs and are swallowed are called ingestant allergens.

• When foods are digested and the nutrients are absorbed, substances in the food (ingestant allergens) stimulate allergic response. These reactions cause a number of allergic symptoms.

Symptoms

• Food allergens ordinarily cause GIT symptoms, but they may also cause

• Skin rash• Puffed lips and tongue• Migranine• Rhinitis • Bronchial asthma • Severe cases of eczema of hands• Atopic dermatitis (such as tomato rash, strawberry

rash, or that caused by eating chocolate, shellfish)

• In food allergy the activity of allergens is not localized in one organ or area of the body, but it is transferred to other organs by the blood.

Source of Ingestant Allergens

• Some of the most common allergens ingested by children are foods considered essential to proper diet and growth such as

• Cow’s milk, orange juice, cod liver oil, vitamin containing fish liver oil.

• Hundreds of extracts of food stuffs are commercially available as a single or multiple units for use by the allergist or diagnostic skin test materials, however, they have little or no value in therapy.

Examples

• Milk Allergy: Milk allergy is a specific immunologic, antigen-antibody response owing partially to lactalbumin. This protein acts as allergen and responsible for antigen-antibody reaction. Because on heating or boiling alter this protein and thus no antigenicity.

Symptoms of food allergy

• Milk allergy may result in • Severe dermatitis • Recurrent rhinorrhea• Bronchitis • Asthma Various commercially milk substitutes that are

prepared from soybean isolates offer a milk-free formula claimed to be devoid antigenicity.

Two of these are Soyalac and Prosobee

• Coffee Allergy:• It has been determined that coffee can produce allergic

response.• Symptoms of Allergy:• Severe migraine, gastroenteritis and widespread hives • Causes:• The principal water-extractable allergenic component

of green coffee is chlorogenic acid (3-caffeoylquinic acid). Some of authorities disagree with this, calming that the coffee roasting process alters its structure.

• Treatment: the main treatment of this type of allergy is to remove that material from food, which cause allergy or hypersensitivity reactions.

• All the allergens are available in the form of extracts, which are obtained from food. These allergens are injected to the hypersensitive person, if he response, he will avoid to take this food.

Injectant Allergy

• The injectants (injectable preparations and insects) cause allergy in a hypersensitive person, allergic condition is known as injectant allergy.

Source of injectant allergy

• Injections • Insects as source of natural injectant allergens• Injections: Allergic reactions to penicillin

injections are well known to most of the lay public. Anaphylactic reactions to penicillin occur with a frequency of 1-5 per 10,000 patient-courses of penicillin.

• Skin test for penicillin allergy is of definite value, but test must be conducted under control

• 6-Amino penicillinic acid (6-APA) and 7-Aminocephalosporanic acid (7-ACA), as well as semisynthetic penicillin's and cephalosporin, cause positive intra-cutaneous reactions in most susceptible persons.

• For this reasons, such antibiotics as the cephalosporin's and semisynthetic penicillin’s should be used with caution by the physicians treating patients that are sensitive to penicillin G.

• In addition to penicillin products, other injectables may cause allergies such as liver extract, antitoxins, and the glandular products.

• Allergic reactions:The allergic reaction is generalized in case of injections, because the injectant allergens enter the blood stream and circulate throughout the body.

• Symptoms: the symptoms in each case are similar to those of the antibiotics;

• Itching of the plasma of the hands and the soles of the feet

• Erythema (redness of skin)• Peeling of skin are characteristic.

• Insects as source of natural injectant allergens:• Bees, hornets and wasps such insects are

considered as source of injectant allergens. • Stings of such insects can induce severe

reactions. In fact it has been estimated that more people die annually from bee sitting and wasps sting than from snakebites.

• Such patient can be immunized by using injections of antigens because one antigen is common to all bees and wasps.

• Research is being conducted on this subject at the present time. Whole insects extracts have been made to determine the optimal method of treatment.

• Bitting arthropods are also subjected to clinical trails among these spiders, mites, lice, chiggers, ticks, sand flies, horse flies, scorpions, centipedes and numerous others indigenous to geographic areas are investigated.

• Allergic reactions: stings of insects can induce severe local and constitutional reactions sometimes causing death.

Contactant Allergens

• Allergens that come into direct contact with the epithelium are called contactant allergens.

• The contactant allergens cause a localized reactions in a particular part of the body.

• Symptoms: The allergic symptoms of the contactant allergens are watery blisters and dermatitis

• Watery blisters: These are white in center and surrounded by red color, associated with pruritis (itching), due to which patient desire to scratch the blisters. The blisters break open and the exuding fluid forms new blisters that spread quite rapidly.

• Source or causes of contactant allergy: there are many substances and products, which are identified as source of contactant allergies, these includes

• Plants or plant products• Aeroallergens • Cosmetics and perfumes etc.

Plants or plant products:• Many substances and products has been recognized as the cause of

contactant allergies.one of the important of this is Poison ivy, Toxicodendron radicans(L) Kuntze, other allergenic species of the genus Toxicodendron include T.diversilobum (T&G) known as western poison oak, T.quercifolium (Michx) known as eastern poison oak etc.

• All these contains the same nonvolatile, phenolic principle urishiol resin, and mainly cause watery blisters.

• Oak: a cupuliferous tree of genus Quercus. The bark of all species contains a large proportion of tannins.

• Quercus: galls for dye and ink

• Other plant excitants such as asparagus (antiseptic), buckwheat, catalpa leaves (asthma), daffodils, English ivy, ginkgo leaves, lobelia (tobbaco), mayapple, osage orange, smartweeds and dozens of other cause dermititis.

Aeroallergens:

• Occasional contactant dermititis has been caused by aeroallergens.

Various pollen grains that contain oils, hairs from different kinds of leaves and flowers, and even small fragments of plant tissue carried by smoke from bush fires, grass fires and burning leaves cause contactant allergy.

Cosmetics and perfumes:

• Cosmetics manufacturing companies remove some known irritants and allergens from there beauty products and consequently use the term hypoallergenic cosmetics to denote this fact.

• An ingredient in “violet” talcum powder is chief source of allergy. Dibromofluorescein, commonly used in lipsticks is another.

• Perfume, soaps and soaps powders, plain detergents, enzyme detergents, nail polishes, nail polishes removers, hair dyes and hair sprays, blankets, wool in clothing are the numerous major causes of contactant dermititis.

Infectant allergens

• The bacterial metabolic wastes are considered as infectant allergens.

• Numerous living organisms may cause allergy through the products they release during their metabolism in the human body.

Source or Cause of infectant allergy:

• Many microorganisms or pathogens certain types of bacteria, protozoans, molds, helminthes, and other parasitic forms by the presence in the body for long time responsible for chronic illness.

• Metabolic products of growth of these organisms may be of such nature that the individual become sensitized.

Bronchiectasis: an example of infectant allergy:The chronic bacterial infection of the bronchioles, where in the constant presence of bacterial wastes may sensitize the allergic individual is the one of the example.The person may exhibit the allergic symptoms but does not respond positively to skin tests for inhalant allergens.

INFESTANT ALLERGENS:

• In a manner somewhat similar to the infectants, parasitic organisms may sensitize the human body.

• Invasions of hookworms, tapeworms, pinworms, threadworms, dermatophytes and other forms have caused allergic response in susceptible individuals.

• Growth products and metabolic wastes of these parasites are constantly present in the body and referred to as infestant allergens.

Case History:

• To determine the circumstances surrounding the patient’s allergy, the allergist must record all the details regarding the allergic attacks, including data on the type of occupation and the familial background. All the information's concerning with patient like mode of onset of past symptoms, cause of recent attack is recorded in the case history.

• A stated on a typical case history report, the entries include:

• Name and sex• Marital status• Occupation• Chief complaint

• First attack:• Present illness• Age of onset (time of development of symptoms)• Date of first attack• Place, time and mode of onset• Seasonal variation • Duration • What relieves attack

• Present attack:• Date of onset i.e. when the symptoms developed• Place of onset i.e. where the symptoms develop• Mode of onset i.e. how the symptoms develop• Sneezing • Nasal discharge• Wheeze• Cough• Headache

• Symptoms affected by:• Meals• Drugs• Exertion• Excitement • Weather changes• Wind• Smoke or fumes • Time of day • Moving in lawn• Rain

• Automobile rides • Playing golf• Riding horse • Cleaning house • Change of season • Change of environment• Change of occupation

• Other points of information include the types of medication the patient may take and condition of home environment (heating system, type of floor covering, presence of house mold pests, nature of bed cover and pillows etc). A past medicine history may be requested. Allergic symptoms of the paternal and maternal relatives are frequently a clue.

• A complete case history includes both a physical and a laboratory examination, the latter to include reports of urine, blood, sputum, and nasal smears. In addition, results of radiograph and electrocardiogram are customary. Following lab tests the allergist makes his diagnosis and attempts to confirm it by the use of skin tests.

Skin tests:

• Skin tests are conducted in 2 principal ways • 1. Scratch test: it is similar to smallpox

vaccination, i.e., scratching the skin and introduce an extract of the allergic substances.

• 2. intradermal(intra-cutaneous) tests: in which a small quantity of the extract is injected between the layers of the skin.

• Allergenic extracts are stable preparations of various antigenic substances and are used for diagnosis, pre-seasonal prophylaxis and treatment of allergies (except food allergens).

• In each case allergenic extract represents a solution of the chief constituents of the tested material. (preparation of extracts involves the use of one of several standard extracting fluids. Coca’s fluid, normal saline solution, purified water, dilute glycero-dextrose solution etc ).

• By injecting small amount, usually 0.1ml, into the arm of the patient, the allergist can observe the resulting reaction within 20 minutes and classify it using the scheme.

• A skin test, then, is actually a localized reaction that determines whether the patient responds to the particular allergen. skin test are quite useful in determining sensetivity to inhalant, injectants, contactants and some ingestants although the reactions in ingestants are less reliable.

• Normally contactants are applied as patch test, where the material is applied directly to the skin which is neither scratched nor penetrated with a needle. As a general rule, patch test require a much longer time for the reaction to occur at least 48 hours but sometime 4-5 days.

• Other tests, such as ophthalmic test, microscopic examination of nasal secretions, passive transfer test employed by physician as occasion demands.

Clinical designation of skin reactions

Designation Symbol Characteristics

Negative _ No reaction or no different than control

Doubtful _+ No appreciable difference from control other than slight erythema

One plus + Erythema smaller than 20mm in diameter

Two plus ++ Erythema larger than 20mm in diameter but no wheal

Three plus +++ Definite wheal with surrounding erythema

Four plus ++++ Wheal with definite pseudopods and erythema

Treatment

• Allergy may treated by several ways • Immunotherapy• Drugs therapy• Removal of allergens• Avoiding of suspected foods

Immunotherapy or hyposensitization treatment

• It is a type of treatment in which the allergist suggests a serious of injections of offending allergens.

• These injections are known as allergy shot. They are injected at regular intervals. For safety reasons, the injections begins with small allergens dose, the amount of allergens increased weekly, until a high dose of injected allergens are reached. These injections or allergic shot desensitize the patient to the allergens due to which the allergic response is reduce.

Purpose of immunotherapy

• The purpose is to produce blocking or neutralizing antibodies. These antibodies provide a protective response in the cells. As a result allergens are prevented from

• When this blocking is achieved then little or no histamine is released due to which allergic symptoms are reduced.

• Example of pollen allergy:• If the patient has a case history of allergy and have

exhibits a positive reaction to ragweed pollen extract, the allergist will probably resort to the hyposensitization method of treatment.

• At regular intervals a measured amount of diluted extract is injected subcutaneously. The dose is gradually increased until the patient can withstand the inhalation of the normal seasonal atmospheric conc: of regweed.

• Complete freedom from is rarely accomplished because of inadequacy of the extraction fluids,

• In addition because the identity of allergenic fraction has not been established chemically, it can not be assayed in the completed extract.

• Pollen extracts are made on the wt, volume basis and are standardized according to the no. of pollen units, protein nitrogen unit or depending on the laboratory policy.

• One pollen unit represent the activity in 0.001 mg of pollens.

• Most of researcher has concentrated on ragweed, although it has numerous advantages. Much of this researchers involves the use of selective extracting fluids. Such as preparation of alum-precipitated and ammonium sulfate treated extracts the application of chromatographic and electrophoretic means of analysis.

• If the treatment is conducted prior to the time of pollination of the plants it is termed as pre-seasonal.

• If maintained throughout the year for some allergy is called perennial

• And if instituted during the symptomatic period is called co-seasonal.

Effectiveness of immunotherapy

• Allergen immunotherapy is effective in overcoming stinging insect allergies. These are dangerous allergies and if it is untreated can result in fatal allergic reactions. The patient is given small injections every 20-30 minutes for at least several hours. As a result immunity is developed with in 10-14 days. This type of immunotherapy is also effective for severe hay fever and also in chronic allergic asthma.

• It is also useful for contactant allergy.

Drug Therapy

• For most of the patients having allergies, medicines are used to begin therapy, for example.

• Most forms of hay fever are easily controlled with antihistamine drugs. The antihistamine only prevent the release of histamine. The could not prevent the antigen antibodies reactions. Antihistamine relieves symptoms such as itching, and sneezing produce by histamine.

• Asthma is usually treated with medications taken orally are inhaled in vapor form. Asthma medications includes bronchodilators and anti-inflammatory steroids, which inhibits the immune response that cause air-way inflammation.

• In case of anaphylactic shock emergency treatment with an injection of adrenaline also called epinephrine is required. This injection quickly widens blood vessels and open up constriction airways.

Removal of allergens

• In many cases the best treatment of the allergy is removal of the offending allergens from the patient environment, if possible. If pet animals are the case of allergens then the effective is to remove that pet animal. Although the patient also given desensitizing injections containing extracts but most easy way is to remove animals which case allergy.

• Some allergens such as plant pollens are impossible to remove because they flout freely in the air.

Avoiding of suspected foods

• Food allergens are difficult to diagnose and treat than other allergens, because skin test are un reliable and blood tests may be doubtful. Therefore when a particular food is suspect i.e. is allergenic to the patient, then the patient should avoid it. If the patient does not know about the allergenic food, the allergist will suggest a special diet to the patient. This diet is simple and free from various foods.

• After this the allergist will reintroduce each of the foods one at a time to identify that which type of food acts as offending allergens. When this food is detected, the patient is advised to avoid such food.

Allergy may develop at any agereport of the patient receiving medical attention in survey of 31831 persons.

Asthma & Hay fever Other allergies

Age group Male Female Male Female

0-4 22.5 19.8 47.3 49.6

5-14 58.5 37.5 45.2 48.9

15-24 71.3 50.0 18.5 47.9

25-44 49.4 64.0 18.5 42.2

45-64 40.2 43.3 18.7 33.3

65 and over 46.3 24.8 11.2 23.4

Is the hereditary factor important When both parents are allergic 75% of offspring may develop allergy

When one parent is allergic 25.50% of offspring may develop allergy

When neither parent is allergic 7.12% of offspring may develop allergy

• The durham sampler method is used to determine the pollen count is the gravity method in which a microscope slide is rubbed with a petrolatum mixture and is exposed in a standard exposure device for 24 hour period.

• The pollen count represent the number of pollen grains per square cm of slide surface.

• The pollen must contain an excitant of hay fever.

• The pollen are anemophilous or wind borne.• They are produce in large quantity.• The plant producing the pollen are widely

distributed. • The American Academy of Allergy has

established a chart for the ragweed index of the principle cities.

Trees: the spring flowering trees may be subdivided into early and later spring.Early spring trees: Ulmus americana LAcer rubrum LPopulus deltoides Marsh

• Later spring season:• Betula papyrifera Marsh• Betula lenta L• Juglans nigra L• Grasses: the most important grass of U.S are • cynodon dactylon• Phelum pratense • Anthoxanthum odoratum L