Types of hypersensitivity Types of hypersensitivity diseasesdiseases

The type of immune response and The type of immune response and immunologic mechanisms that causes immunologic mechanisms that causes tissue injurytissue injury

The nature and location of the antigen The nature and location of the antigen that is the target of this response.that is the target of this response.

Types of hypersensitivity Types of hypersensitivity diseasesdiseases

Immediate H.S (Type I) caused by IgEImmediate H.S (Type I) caused by IgE Type II H.S caused by antibodies other than Type II H.S caused by antibodies other than

IgE can cause tissue injury and interfering with IgE can cause tissue injury and interfering with normal cellular functions.normal cellular functions.

Type III H.S caused by deposition of circulating Type III H.S caused by deposition of circulating Immune complexes in tissuesImmune complexes in tissues

Type IV or Delayed type hypersensitivity Type IV or Delayed type hypersensitivity caused by T cells and Macrophagescaused by T cells and Macrophages

*Activation of Th2 cells and production of *Activation of Th2 cells and production of IgEIgE

*Allergen Activation of Th2 B *Allergen Activation of Th2 B cell activation IgE binding of IgE cell activation IgE binding of IgE to Fc receptor reexposure to Allergento Fc receptor reexposure to Allergen

release of mediators pathologic release of mediators pathologic reactions reactions

Disease caused by Disease caused by Immune responsesImmune responses

General features (1)General features (1)

Immediate Immediate hypersensitivityhypersensitivity

، آلرژن ورود ، با آلرژن ورود باآن آن BBسلولهای سلولهای

از وپس از راشناسایی وپس راشناساییبادی آنتی ، شدن بادی فعال آنتی ، شدن فعال

IgEIgE. میکنند میکنند .ترشح ترشح

General features(2)General features(2)

There is a strong genetic predisposition for the There is a strong genetic predisposition for the development of immediate hypersensitivitydevelopment of immediate hypersensitivity

*high level of IgE synthesis often run in families*high level of IgE synthesis often run in families• Class –II MHC allelesClass –II MHC alleles• One locus for atopy is on chromosome 5,near One locus for atopy is on chromosome 5,near

the site of gene cluster encoding the IL-3,IL-4,the site of gene cluster encoding the IL-3,IL-4,• IL-5,IL-9,IL-13 and IL-4RIL-5,IL-9,IL-13 and IL-4R

آنتي عوامل مقابل در آلرژيك يا آتوپيك آنتي افراد عوامل مقابل در آلرژيك يا آتوپيك افراددر موجود هاي ،پروتئين محيطي شايع در ژنيك موجود هاي ،پروتئين محيطي شايع ژنيك

گياهان گياهان گرده فضوالت ))pollenpollen((گرده ، غذايي مواد فضوالت ، ، غذايي مواد ،طريق از داروها برخي يا حشرات سم طريق حيواني، از داروها برخي يا حشرات سم حيواني،

Th2Th2 ميدهند ميدهند پاسخ پاسخ باال حالليت با مولكول ريز پروتئينهاي باال آلرژنها حالليت با مولكول ريز پروتئينهاي آلرژنها كنند نمي فعال را ذاتي كنند ايمني نمي فعال را ذاتي ايمني مكرر وبرخورد محيط در مكرر فراواني وبرخورد محيط در فراواني باال باال گليكوزيالسيون گليكوزيالسيون

General featuresGeneral features

��AllergensAllergens

Type I is dependent on the activation of Th2 Type I is dependent on the activation of Th2 cellscells

The clinical and pathologic manifestations of The clinical and pathologic manifestations of Type I:increased vascular Type I:increased vascular permeability,vasodilation,smooth muscle permeability,vasodilation,smooth muscle contraction,local inflammationcontraction,local inflammation

Mast cell activationMast cell activation

Eosinophil and BasophilEosinophil and Basophil

اين سلولها داراي گيرنده اين سلولها داراي گيرنده IgEIgE براي براي high affinityhigh affinityهاي هاي

مي باشند مي باشندFCFCRRبنام بنام گرانولهايي سيتوپالسمي كه گرانولهايي سيتوپالسمي كه

حاوي آنزيم ها و ساير حاوي آنزيم ها و ساير مدياتورهاي فارماكولوژيكمدياتورهاي فارماكولوژيك

Mast cell activationMast cell activation

Rapid release of granule Rapid release of granule contents(degranulation)such as contents(degranulation)such as Histamine,tryptase,chymase,proteoglycaHistamine,tryptase,chymase,proteoglycansns(heparin and chondroitin sulfate)(heparin and chondroitin sulfate)

Synthesis and secretion of lipid Synthesis and secretion of lipid mediators(prostaglandines ,Leukotrienes)mediators(prostaglandines ,Leukotrienes)

Synthesis and secretion of cytokines(IL-Synthesis and secretion of cytokines(IL-3,4,5,6,TNF-3,4,5,6,TNF-))

Mediators actionsMediators actions

Histamine= bronchoconstrictor,vascular Histamine= bronchoconstrictor,vascular leak,intestinal hypermotilityleak,intestinal hypermotility

PGD2=vasodilator and bronchoconstrictor , PGD2=vasodilator and bronchoconstrictor , neut. Chemotaxisneut. Chemotaxis

LTC4=bronchoconstriction,inflammationLTC4=bronchoconstriction,inflammation PAF=bronchoconstriction ,vasodilator,PAF=bronchoconstriction ,vasodilator,inflammationinflammation

Clinical and pathologic Clinical and pathologic featuresfeatures

Hay fever(allergic rhinitis)Hay fever(allergic rhinitis) Increased peristalsisIncreased peristalsis Bronchial asthmaBronchial asthma AnaphylaxisAnaphylaxis

Wheal and Flare reactionWheal and Flare reaction

Skin test(PK test)Skin test(PK test)

TherapyTherapy

Inhibiting mast cell degranulationInhibiting mast cell degranulation Antagonizing the effects of mediatorsAntagonizing the effects of mediators Reducing inflammationReducing inflammation DesensitizationDesensitization

Anti IgE as a therapyAnti IgE as a therapy

Severe allergic reactions during Severe allergic reactions during anesthesia are fortunately rare, occurring anesthesia are fortunately rare, occurring only once in every 5,000 to 25,000 only once in every 5,000 to 25,000 anesthetics. Unfortunately, these anesthetics. Unfortunately, these reactions can sometimes be fatal, with a reactions can sometimes be fatal, with a 3.4% mortality3.4% mortality

Anaphylaxis during general (asleep) anesthesia Anaphylaxis during general (asleep) anesthesia presents in a similar way but there are three unique presents in a similar way but there are three unique features:features:

First, the patient who is asleep cannot tell us about light-First, the patient who is asleep cannot tell us about light-headedness or breathlessnessheadedness or breathlessness

Second, during a typical general anesthetic, many drugs Second, during a typical general anesthetic, many drugs are given, and it is hardly ever clear which of these are given, and it is hardly ever clear which of these drugs have caused the reactiondrugs have caused the reaction

Third, during anesthesia there are many other potential Third, during anesthesia there are many other potential causes for the blood pressure to be dropping or the air causes for the blood pressure to be dropping or the air passages to be closing offpassages to be closing off

Treatment may include insertion of a breathing Treatment may include insertion of a breathing tube, administration of intravenous fluids, and a tube, administration of intravenous fluids, and a variety of drugs, the most important of which is variety of drugs, the most important of which is epinephrine (adrenaline). Early and appropriate epinephrine (adrenaline). Early and appropriate treatment is almost always successful. treatment is almost always successful.

drugs are not the only cause of allergic reactions, drugs are not the only cause of allergic reactions, and a recently recognized cause of anaphylaxis is and a recently recognized cause of anaphylaxis is allergy to natural rubber (or `latex`). Reactions to allergy to natural rubber (or `latex`). Reactions to latex are a special problem during anesthesia as latex are a special problem during anesthesia as surgical gloves are usually made of this material. surgical gloves are usually made of this material.

Food AllergyFood Allergy

Introduction to food Introduction to food allergiesallergies

When people have an unpleasant reaction to something they ate, When people have an unpleasant reaction to something they ate, they often think that they have an allergy to the food. Actually, they often think that they have an allergy to the food. Actually, however, only about 10-15% of adults and children have clinically however, only about 10-15% of adults and children have clinically proven true allergic reactions to food.proven true allergic reactions to food.

This difference between the prevalence of clinically proven food This difference between the prevalence of clinically proven food allergy and the public's perception of the problem is due primarily allergy and the public's perception of the problem is due primarily to misinterpreting food intolerance or other adverse reactions to to misinterpreting food intolerance or other adverse reactions to food as food allergyfood as food allergy

A true food allergy is an abnormal response to food that is A true food allergy is an abnormal response to food that is triggered by a specific reaction in the immune system and triggered by a specific reaction in the immune system and expressed by certain, often characteristic, symptoms. expressed by certain, often characteristic, symptoms.

People who have food allergies must identify and prevent them People who have food allergies must identify and prevent them because, although usually mild and not severe, these reactions because, although usually mild and not severe, these reactions can cause devastating illness and, in rare instances, can be fatal.can cause devastating illness and, in rare instances, can be fatal.

food intolerancefood intolerance Food allergyFood allergy food poisoningfood poisoning

Histamine toxicityHistamine toxicity: Some natural substances (for example, : Some natural substances (for example, histamine) in foods can cause reactions resembling allergy. histamine) in foods can cause reactions resembling allergy. Histamine can reach high levels in cheese, some wines, and Histamine can reach high levels in cheese, some wines, and certain fish, particularly tuna and mackerel. certain fish, particularly tuna and mackerel.

Food additivesFood additives: Another type of food intolerance is an : Another type of food intolerance is an adverse reaction to certain compounds that are added to adverse reaction to certain compounds that are added to food to enhance taste, provide color, or protect against the food to enhance taste, provide color, or protect against the growth of microorganisms. growth of microorganisms.

The compounds most frequently tied to adverse reactions The compounds most frequently tied to adverse reactions that can be confused with food allergy are :that can be confused with food allergy are :

yellow dye number 5yellow dye number 5 monosodium glutamate (MSG) (MSG) and sulfites. and sulfites.

The allergens in foodThe allergens in food

Resist the heat of cookingResist the heat of cooking The acid in the stomachThe acid in the stomach The intestinal digestive enzymes. The intestinal digestive enzymes. The allergens survive to cross the The allergens survive to cross the

gastrointestinal lininggastrointestinal lining enter the bloodstream, enter the bloodstream,

What are the most common What are the most common food allergies?food allergies?

In adults, the most common foods that In adults, the most common foods that cause allergic reactions arecause allergic reactions are shellfish, shellfish, such as shrimp, crayfish, lobster, and crab; such as shrimp, crayfish, lobster, and crab; nuts from trees, such as walnuts; fish; nuts from trees, such as walnuts; fish; eggs; ; and and peanuts..

In children, the pattern is somewhat In children, the pattern is somewhat different from adults, and the most common different from adults, and the most common foods that cause allergic reactions are eggs, foods that cause allergic reactions are eggs, milk, peanuts, and fruits, particularly milk, peanuts, and fruits, particularly tomatoes and strawberries. tomatoes and strawberries.

What is cross-reactivity?What is cross-reactivity?

Cross-reactivity is the occurrence of Cross-reactivity is the occurrence of allergic reactions to foods that are allergic reactions to foods that are chemically or otherwise related to foods chemically or otherwise related to foods known to cause allergy in an individual. known to cause allergy in an individual.

What are the symptoms and What are the symptoms and signs of food allergy?signs of food allergy?

All of the symptoms of food allergy occur within a few minutes to an hour All of the symptoms of food allergy occur within a few minutes to an hour of eating. of eating.

A food allergy can initially be experienced as an A food allergy can initially be experienced as an itching in the mouth and in the mouth and difficulty swallowing and breathing. difficulty swallowing and breathing.

Then, during digestion of the food in the stomach and intestines, Then, during digestion of the food in the stomach and intestines, symptoms such as symptoms such as nausea, vomiting, , diarrhea, and , and abdominal pain can can start. start.

Incidentally, the gastrointestinal symptoms of food allergy are those that Incidentally, the gastrointestinal symptoms of food allergy are those that are most often confused with the symptoms of different types of food are most often confused with the symptoms of different types of food intolerance.intolerance.

the allergens are absorbed and enter the bloodstream. When they reach the allergens are absorbed and enter the bloodstream. When they reach the skin, allergens can induce the skin, allergens can induce hives or or eczema, and when they reach the , and when they reach the airways, they can cause asthma.airways, they can cause asthma.

As the allergens travel through the blood vessels, they can cause As the allergens travel through the blood vessels, they can cause lightheadedness, weakness, and anaphylaxis, which is a sudden drop in lightheadedness, weakness, and anaphylaxis, which is a sudden drop in blood pressure. blood pressure.

What was the timing of the reaction? Did the reaction come on quickly, usually within an hour after eating the What was the timing of the reaction? Did the reaction come on quickly, usually within an hour after eating the food?food?

Was treatment for allergy successful? For example, if hives stem from a food allergy, antihistamines should Was treatment for allergy successful? For example, if hives stem from a food allergy, antihistamines should relieve them.relieve them.

Is the reaction always associated with a certain food?Is the reaction always associated with a certain food?

Did anyone else get sick? For example, if the person has eaten fish contaminated with histamine, everyone who Did anyone else get sick? For example, if the person has eaten fish contaminated with histamine, everyone who ate the fish should be sick. In an allergic reaction, however, only the person allergic to the fish becomes ill.ate the fish should be sick. In an allergic reaction, however, only the person allergic to the fish becomes ill.

How much did the patient eat before experiencing a reaction? The severity of the patient's reaction can How much did the patient eat before experiencing a reaction? The severity of the patient's reaction can sometimes relate to the amount of the suspect food eaten.sometimes relate to the amount of the suspect food eaten.

How was the food prepared? Some people will have a violent allergic reaction only to raw or undercooked fish. A How was the food prepared? Some people will have a violent allergic reaction only to raw or undercooked fish. A thorough cooking of the fish destroys those allergens in the fish to which they react, so that they then can eat it thorough cooking of the fish destroys those allergens in the fish to which they react, so that they then can eat it with no allergic reaction.with no allergic reaction.

Were other foods eaten at the same time as the food that caused the allergic reaction? Fatty foods can delay Were other foods eaten at the same time as the food that caused the allergic reaction? Fatty foods can delay digestion and thus delay the onset of the allergic reaction. digestion and thus delay the onset of the allergic reaction.

Cromolyn sodiumCromolyn sodium Theophyllin blocks phosphodiesteraseTheophyllin blocks phosphodiesterase epinephrinepinephrin

How is food allergy How is food allergy diagnosed?diagnosed?

HistoryHistory Elimination dietElimination diet Skin testsSkin tests Blood testsBlood tests Food challengeFood challenge

scratch testscratch test

to test a number of potential allergens at one timeto test a number of potential allergens at one time

InexpensiveInexpensive

less sensitiveless sensitive

The size of the hive may correlate with the intensity of the The size of the hive may correlate with the intensity of the allergic reaction.allergic reaction.

In the event of a severe reaction, the allergist will administer a In the event of a severe reaction, the allergist will administer a rescue medication such as epinephrine or an antihistaminerescue medication such as epinephrine or an antihistamine

necessary to remove the patient from an anthihistamine necessary to remove the patient from an anthihistamine medication regimenmedication regimen

RAST test RAST test or radioallergosorbent or radioallergosorbent expensiveexpensive considered as accurate as food challengesconsidered as accurate as food challenges they are considered a very safe way to test for food they are considered a very safe way to test for food

allergiesallergies less sensitive than skin prick testsless sensitive than skin prick tests a positive RAST test will be often be confirmed a positive RAST test will be often be confirmed

with a food challengewith a food challenge

RIST(radiolabeled Immunosorbent test)RIST(radiolabeled Immunosorbent test)

The suspected allergen is bound to an insoluble material and the patient's The suspected allergen is bound to an insoluble material and the patient's serum is added. If the serum contains antibodies to the allergen, those serum is added. If the serum contains antibodies to the allergen, those antibodies will bind to the allergen. Radiolabeled anti-human IgE antibody is antibodies will bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble added where it binds to those IgE antibodies already bound to the insoluble material. The unbound anti-human IgE antibodies are washed away. The material. The unbound anti-human IgE antibodies are washed away. The amount of radioactivity is proportional to the serum IgE for the allergen.amount of radioactivity is proportional to the serum IgE for the allergen.

RAST are often used to test for allergies when:RAST are often used to test for allergies when:• a physician advises against the discontinuation of medications that can • a physician advises against the discontinuation of medications that can interfere with test results or cause medical complications;interfere with test results or cause medical complications;• a patient suffers from severe skin conditions such as widespread eczema or • a patient suffers from severe skin conditions such as widespread eczema or psoriasis; orpsoriasis; or• a patient has such a high sensitivity level to suspected allergens that any • a patient has such a high sensitivity level to suspected allergens that any administration of those allergens might result in potentially serious side administration of those allergens might result in potentially serious side effects.effects.