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Hypersensitivity causes reproducible symptoms triggered by exposure to specific stimuli tolerated by others. Allergens penetrate through skin, mucosal membranes, injections, or internal production. Sensitization typically occurs after repeated exposure, leading to abnormal immune responses. Allergies manifest as hypersensitivity reactions mediated by immunological mechanisms, such as IgE antibodies. Historical figures like Robert Koch and Charles Richet have advanced our understanding of these complex reactions, leading to terms like "anaphylaxis" and "serum sickness." Current diagnostics include skin testing to identify specific allergens.
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HYPERSENSTIVITY Hypresensitivitycausesreproduciblesymptoms and singsinitiated by exposure to definedstimulusthatistolerated by „normal” people
Whathappensinallergy? Firstly, allergens gain access via: • skin • mucosalmembrane • injection (stings, bites, drugs) or • endogenous production (autoallergens or allergens produced by invadingparasites). • Sensitisation to the allergen occurs usually after repeated exposure or in young children before completetolerancehasoccurred.
Whatis… • Allergy– hypersensitivity reactioninitiated byimmunologicmechanism. Itcan be eitherantibody(IgA, E, G) orcellmediated. Reactingerroneously to externalmaterial to which it normally shouldn’t react. • Allergen – special type of (otherwise harmless) Agsthatelicit allergic reactions in sensitised individuals. Usually enter via skin ormucosalmembrane. Potentialallergenscan be anythingfromdustmites, pollen, insectstings, fragrances, foods. • Atopy–the genetic propensity to develop an IgEAbresponse to common allergens. Asthma is one of themost common clinical manifestations of this. • Atopicallergens – IgE-inducingallergens.
1892 - Robert Koch • Discovererof tuberclebacillus • Attempted to prevent TB by inoculation withbacillusextract • Unfortunately:‣-No protection for naive individuals. ‣-Reactivateddiseaseinexposed • But: intradermal injection of bacillusextract in previously exposed individualsresulted in a stereotypic induratedlesionwithin48-72 hours.
1893 - Emil von Behring • Workingwithdiphtheriatoxin noted that animals would suffer enhancedresponses and even death following a second dose of toxin too small to injure normaluntreatedanimals • Describedthisphenomenonas“hypersensitivity”
1902 - Charles Richet andPaul Portier • On the yacht of the Prince of Monacco to study the effects of marinetoxinsinmammals • Attempted to protect dogs from the effects of toxins atlowdoses • Re-exposureto innocuousdoses resulted in a rapid shock and Suffocation • Coined the term “ana-phylaxis” toemphasize its antithesis to thefamiliar“prophylaxis”
1903 - Maurice Arthus • Described a stereotypical responseinrabbitsfollowing repeatedintradermalinjection of protein antigens • Theresponse, characterized by localerythema, induration, hemorrhage and necrosis became known as the “Arthus Reaction”
1906 - Clemens von Pirquetand Bela Schick • The term “serum sickness” to describestrangesystemicsymptoms suffered by some patients weeks after receiving diphtheria or tetanus anti-toxinhorse serum • Postulated for the first time that thesehypersensitivityreactionsmight be the product of immune response • Namedtheseresponses “allergic” from the Greek allosergos, alteredreactivity
1942 - Karl Landsteinerand Merrill Chase • Demonstrated transfer of tuberculin test sensitivityin guineapigs • Sensitivityistransferredfrom TB-exposed to un-exposed animalswithleukocytetransfer, but not with serum transfer
1966 K. Ishisaka & T. Ishizaka • The role of IgE Class Antibodies was first indentified by Kimishige and Teruko Ishizaka. IgE is one of the elements that come into play when a person first develops allergic sensitivity.
1980 BengtSamuelsson • Received the Nobel Prize for his research on leukotrienes—this greatly increased the understanding of how the body’s own “mediators” in asthma, allergies and inflammation.
Hypresensitivitycausesreproduciblesymptoms and singsinitiated by exposure to a definedstimulusthatistolerated by „normal” people • Non allergichypersensitivity- describehypersensitivityinwhichimmunologicalmechanismscan not be proven!!!
Non allergicasthma- thisisthepreferred term for non – immunologicaltypes of asthma. • Allergicasthma- asthmamediated by immunologicalmechanisms. IgEantibodiescaninitiateboth an immediate and a lateasthmaticreaction. T cells associated reactionsseem to be importanceinthelate and delayedreactions
Foodallergy „Oralallergysyndrome”- subjectswithrhinitis and asthmadue to pollen allergymayhavesymptoms on oralexposure to oftenunstablefoodallergens, whichmay show structuralsimilarities to pollen allergens; reaction to birch pollen and appleorhazelnuts, mugwort pollen and celery.
Anaphylaxisis a severe life threatening, generalizedorsystemichypersensitivityreaction. • Thereaction most oftenstartingwithitching of thegumsthroat, thepalms, orthesoles, and localurticaria, developing to a multiple organ reactionoftendominated by severeasthma and culminatinginhypotension and shock.
Documentingallergicsensitivity: skin tests • If we suspectthattheallergiesarecaused by airborneallergens we do skin pricktests • Allergenic extract (airborne, food, venom) is introduced by prick or on intracutaneously • Sensitization is evident within 15-20 minutes as a wheal attheallergenintroductionsite
Documentingallergicsensitivity: skin tests • skin tests will be less sensitive during the use of antihistamine, corticosteroid and antidepressant.
Skin prick test • Prick testing involves applying a small amount ofan allergen to the skin as well as positive andnegativecontrols (histamine, water/solution) • This investigates the presence of Type I hypersensitivity(but 20% falselypositive and 20% falselynegative) • Type I can also be investigated by bloods testschecking RAST (IgEantibodies)levels to specific allergens
Radioallergosorbent Test (RAST) • Allergens are chemically bound to insolublematrix • Patientsserum added • Any allergen specific IgE binds to the testallergen • Radioactively labelledIgE added which attaches to specific IgE already bound to allergen • Quantitativereadingtaken • Can sometimes miss allergy • Positive results do not always indicate a reaction will happen
Patchtests • Patch testing involves applying allergens to the skin under occluding tapes (usually to the back) for 48 hours. • Readings are taken by examining the skin at 48 hours and 72 & 96 hours for evidence of eczema localised to the site of the allergen • This is used to diagnose Type 4 hypersensitivity (Not urticariaorangiooedema)
