HYPERSENSITIVITY

HYPERSENSITIVITY chaleeOutlineHistory DefinitionBasic ConceptsTypes of Hypersensitivity> Characteristics> Components and Cells> Process and Mechanism> Common Diseases

HistoryAllergies Greek = altered reactivity1906 von Pirquet coined term: hypersensitivityIn 1968 Coombs & Gell defined the 4 types of hypersensitivity > are harmful antigen-specific immune responses , occur when an individual who has been primed by an innocuous antigen subsequently encounters the same antigen , produce tissue injury and dysfunction. > over reaction of the immune system to harmless environmental antigensHypersensitivity reactions 4Atopythe genetic predisposition to synthesize inappropriate levels of IgE specific for external allergensAllergenthe antigens that give rise to immediate hypersensitivity5

6Type I IMMEDIATE HYPERSENSITIVITYImmediate means seconds to minutesImmediate Allergic Reactions, which may lead to anaphylaxis, shock, edema, dyspnea death1) Allergen exposure2) IMMEDIATE phase: MAST cell DEgranulation, vasodilatation, vascular leakage, smooth muscle (broncho)-spasm3) LATE phase (hours, days): Eosinophils, PMNs, T-Cells7

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17Allergen PrimaryIndividual Generation IgE Adhesion IgE binds to the FceRI on mast cell and basophil SecondaryAllergen binds to the IgE on primed target cellCrosslikage of FceRI Degranulate and release the biological mediatorsPreformed granule mediatorsNew generated mediatorsHistamine BradykininLeukotrienes PAF Prostaglandin D2Dilate capillaries,increase permeability, increase mucus secretion, contract smooth muscleSystemic anaphylaxisSkinRespiratory tractDigestive tractMechanism of type I hypersensitivity

19TYPE II HYPERSENSITIVITYANTIBODY MEDIATED IMMUNITYAntibodies attach to cell surfacesOPSONIZATIONPHAGOCYTOSISCOMPLEMENT FIXATION (cascade of C1q, C1r, C1s, C2, C3, C4, C5.. )LYSIS (destruction of cells by rupturing or breaking of the cell membrane)20TYPE II DISEASESAutoimmune Hemolytic Anemia, AHAIdiopathic Thrombocytopenic Purpura, ITPGoodpasture Syndrome (Nephritis and Lung hemorrhage)Rheumatic FeverMyasthenia GravisGraves DiseasePernicious Anemia, PA21Understandably, these are all AUTO-immune diseases, or FAILURES of the MHC. Note most are organ-specific (i.e., local) rather than systemic.

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Antigen or hapten on cell Antibody (IgG, IgM)Activate complement Lyse target cellOpsonic phagocytosis NK , phagocyte Stimulate / block Destroy target cellADCCTarget cell injuryChange the function ofTarget cellMechanism of Type II hypersensitivityTYPE III HYPERSENSITIVITYIMMUNE COMPLEX MEDIATEDAntigen/Antibody ComplexesWhere do they go?Kidney (Glomerular Basement Membrane)Blood VesselsSkinJointsCommon Type III Diseases- SLE (Lupus), Poly(Peri)arteritis Nodosa, Poststreptococcal Glomerulonephritis, Arthus reaction (hrs), Serum sickness (days)27An Arthus reaction is a local vasculitis associated with deposition of immune complexes and activation of complement. Immune complexes form in the setting of high local concentration of vaccine antigens and high circulating antibody concentration. Arthus reactions are characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally by necrosis. These symptoms and signs usually occur 412 hours after vaccination. Symptoms can take as long as fourteen days after exposure to appear, and may include signs and symptoms commonly associated withallergic reactionsor infections, such asrashes, itching, joint pain (arthralgia),fever, and swollen lymph nodes (lymphadenopathy), andmalaise. Historically, it was a result of animal serum injections.

28Soluble antigenBodyAntibodyImmune complexSmall molecular soluble Immune complexintermediate molecular soluble Immune complexLarge molecular insoluble Immune complexDeposit on the basement of capillariesCombine and activate complement systemC3a,C5a,C3bInfiltration of neutrophilsPhagocytose complexRelease the enzymes in lysosomeTissue injury Eliminate by phogacytosisPlateletsThrombusAggregation of platletsBlood Clotting MechanismsRelease of vasoactive amineIncrease vascular permeabilityBleeding Edema Basophils and mast cellsRelease of vasoactive amineIncrease vascular permeabilityEdema Local or systemic immune complex diseasesTYPE IV HYPERSENSITIVITY CELL-MEDIATED (T-CELL) DELAYED HYPERSENSITIVITYTuberculin Skin Reaction

DIRECT ANTIGENCELL CONTACTGRANULOMA FORMATIONCONTACT DERMATITIS

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Schematic for granuloma formation in Type IV Hypersensitivity31

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36AntigenT cell(CD4+,CD8+)Secondary contactInducePrimed T cellCD4+ T cellCD8+ T cellReleaseCytokinesIL-2TNF-bINF-gTFMCFMIFMAFSRF

Directly kill target cellsInfiltration of monocyte and Mf

Proliferation of T cell

Exudation and edema

Cytotoxicity Inflammation characterized by infiltration of Mf , monocyte, And tissue injuryMechanism of type IV hypersensitivitySome Parasites that can cause Hypersensitivity Reactions

Trichuris

Trypanosoma

Toxoplasma

Enterobious

Ascaris

Leishmania

Schistosome

Hookworm

Plasmodium

Wuchereria

Onchocerca

Taenia

EnterobiousSoluble antigenBodyAntibodyImmune complexSmall molecular soluble Immune complexintermediate molecular soluble Immune complexLarge molecular insoluble Immune complexDeposit on the basement of capillariesCombine and activate complement systemC3a,C5a,C3bInfiltration of neutrophilsPhagocytose complexRelease the enzymes in lysosomeTissue injury Eliminate by phogacytosisPlateletsThrombusAggregation of platletsBlood Clotting MechanismsRelease of vasoactive amineIncrease vascular permeabilityBleeding Edema Basophils and mast cellsRelease of vasoactive amineIncrease vascular permeabilityEdema Local or systemic immune complex diseases