Dr. Samia Towfeek AL-Shouli Clinical Immunology and Allergy. Foundation...Dr. Samia Towfeek...
Transcript of Dr. Samia Towfeek AL-Shouli Clinical Immunology and Allergy. Foundation...Dr. Samia Towfeek...
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ImmunologyUnitDepartmentofPathology
CollegeofMedicineKingSaudUniversity
Dr.SamiaTowfeek AL-ShouliClinicalImmunologyandAllergy
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ReferenceKuby Immunology7th Edition
2013Chapter15Pages485-510
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Objectives• Toknowthathypersensitivityreactionsareoverandexcessive
immuneresponsesthatcanbeharmfultobodyinfourdifferentways
• TobefamiliarwithinflammatoryprocessesinTypeIhypersensitivityreactionthatmediatesallergicinflammation
• TorecognizethatTypeIIhypersensitivitydealswithimmuneresponsesagainstantigensthatareintegralpartofcellmembraneandareusuallyassociatedwithautoimmunedisorders
• ToknowthatTypeIIIhypersensitivityreactionsaremediatedbyimmunecomplexesandcausevasculitis
• TodescribeTypeIVhypersensitivityisapurelycellmediatedimmuneresponseassociatedwithchronicinflammation
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Whatishypersensitivity?
• Protective immunity:desirablereaction
• Hypersensitivity:undesirablereaction
• Undesirableresponsescanbemediatedby– Antibody binding toantigens(TypesI-III)– Cell mediatedreaction tochemicalsorproteins(TypeIV)
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GelandCoombsClassification
Type I: IgE Ab
Type II: IgGAb to tissue
antigens
Type III: IgG
Immune Complexes
Type IV: Cell Mediated Immunity
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TypeI:ImmediateHypersensitivity
n Mostpeoplewillnotreacttotheseallergensbutsomeindividuals“atopic”respondbyproducinglargeamountsofIgE inresponsetothoseotherwiseharmlesssubstances
n Non-allergic individuals respond to theseallergens by producing IgG antibodies
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Type I Hypersensitivity• Also termed as:
Immediate Hypersensitivity
Allergic reactions
Anaphylactic reactions are severe and rapidly progressing systemic forms which can be quickly life threatening
(Occurs within minutes to hours)
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Features
- Antibody type: IgE
- Cellular components: Mast cells, basophiles & eosinophils
- Antigens:Also known as allergens (antigens with low molecular weight & highly soluble)
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Allergensn SomeoftheallergensinvolvedintypeIhypersensitivityare:pollens,dustmiteallergens,animaldander,nuts,shellfish,variousdrugsetc
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Type I Reaction occur in 2 phases:
• Phase I :- Sensitization phase .
Allergen enter tissues , induce an immune response . B – cells transformto plasma cells & produce IgE.
- IgE bind to receptors on Mast cells andbasophiles ( F c ЄRI - high affinity receptors).
individuals become :
“ Sensitized . “
Type I reactions occur in two phases
• Phase I :- Sensitization phase .
Allergen enter tissues , induce an immune response . B – cells transformto plasma cells & produce IgE.
- IgE bind to receptors on Mast cells andbasophiles ( F c ЄRI - high affinity receptors).
individuals become :
“ Sensitized . “
- Sensitization phase First contact with allergens
- Challenge phaseSubsequent contact with allergens
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TypeIHypersensitivity(Immediate)
Sensitization
Challenge
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October25,2020 Med1 12
PrimaryandSecondaryMediators
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Allergyisasystemicdisorder
NosePharynx
Stomach
EsophagusLungs
Skin
Foodallergy
AllergicrhinitisAsthma
EczemaUrticariaAllergicdermatitis
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Allergy:Rhinitis,Eczema&Conjunctivitis
Normalnose
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* Injected allergens:
Hymenoptera (bees, wasps, ants) sting venom enters the blood stream
à Systemic inflammation
à Anaphylactic shock(life - threatening)
vAnaphylactoid reactions:-Are non - IgE mediatedmay result from contrast media orlocal anesthetics
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Skin Prick testDiagnosisofAllergy
1. Skin prick test (SPT)
2. Specific IgE measurement (RAST)
3. Elimination / Provocation test (Food allergy)
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• Features:-- IgG (orIgM)- Antigens:boundtocellmembranes
(Selfantigens)- Exogenousantigens
(microbial)
- Complementactivation
(Invariable)
TypeIIHypersensitivityReactions
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Clinical examples:
Glomerulonephritis (anti-glomerularbasement membrane)
Mis-matched blood transfusion
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Diagnosis
- Detection of antibodies and antigens by Immunofluoresence in tissue biopsy specimens e.g. kidney, skin etc.
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TypeIII:Immunecomplexhypersensitivity
n Whenanantigenreactswithanantibodytheproducttheyformiscalledanimmunecomplexwhichiscapableofinducinganinflammatoryresponse
n Immunecomplexesaredepositedintissueslikekidneys(nephritis),joints(arthritis)orbloodvessels(vasculitis)
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Type III Hypersensitivity (immune–complex mediated)
• FeaturesAntibody (IgG/ or IgM) + Antigen (soluble)
- Immune – Complex formation
- Complement activation
- Attraction of inflammatory cells
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TypeIIIReactions
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Type III Hypers. ReactionsClinical examples:
Glomerulonephritis: Rheumatoid arthritis, SLE
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Diagnosis of Type III Hypers. Reactions
Demonstration of specific immune complexes in the blood or tissues by:
Immunofluoresence
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TypeIVhypersensitivityreactions(DelayedHypersensitivity)
• Features• Cellmediatedimmuneresponse
– AntigendependentTcell(CD4generallyandCD8occasionally)activationviaMHCClassIorII
• Activatedmacrophages• Delayedonset(2-4days)• Abnormalcellularresponse
– (Granuloma formation)
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Mediators released by TDTH cells
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Development of DTH Response
Sensitization phase:1-2 week period
Effector phase:24-72 hours
Effector cells(activated macs)act non-specifically
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Pathophysiology of Contact dermatitis.
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Type IV clinical examples:
Contact dermatitis
TB granuloma(persistent antigen)
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Diagnosis (Type IV)
1. Delayed skin test (Mantoux test)
2. Patch test (Contact dermatitis)
3. Lymphocyte transformation test
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Skin Patch Test
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TakeHomeMessage
• 1. TypeI(IgE),II(IgG)andIII(IgG)hypersensitivityreactionsaremediatedbyantibodies whereasTypeIVhypersensitivityreactionisacellmediatedimmuneresponse.
• 2. Hypersensitivityreactionsareundesirable,excessive,andaberrant immuneresponsesassociatedwithdisorderssuchasallergy,autoimmunityandchronicinflammation.