Disorders of Immunity and Inflammation

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Disorders of Immunity and Inflammation. Hypersensitivity. Exaggerated Immune Response. Hypersensitivity Types. Allergy Exogenous, non-human antigen Isoimmunity (alloimmunity) Exogenous, human antigen Autoimmunity Endogenous antigen. Hypersensitivity Mechanisms. Type I: IgE mediated - PowerPoint PPT Presentation

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  • Disorders of Immunity and Inflammation

  • HypersensitivityExaggerated Immune Response

  • Hypersensitivity TypesAllergyExogenous, non-human antigenIsoimmunity (alloimmunity)Exogenous, human antigenAutoimmunityEndogenous antigen

  • Hypersensitivity MechanismsType I: IgE mediatedType II: Tissue specificType III: Immune complex mediatedType IV: Cell mediated

  • Type I

    Immediate hypersensitivityIgE mediatedExogenous antigen

    Most (but not all) Allergies

  • Type I: MechanismRepeated antigen exposure causes increased IgE productionIgE binds to mast cellsSensitization occurs

  • Type I: MechanismAntigen binds to IgE on mast cell membraneMast cell releases histamine, chemotaxic factorsInflammatory response occurs

  • Type I: Signs/SymptomsClinical signs, symptoms = response to histamine releaseGI, skin, respiratory systemHigh mast cells numbersMost sensitive

  • Type I: Signs/SymptomsHistamine effectsVasodilatationIncreased capillary permeabilityNon-vascular smooth muscle spasm

  • Type I: Signs/SymptomsSkin: flushing, itching, edema, urticaria, hivesRespiratory: bronchospasm, laryngospasm, laryngeal edemaCardiovascular: tachycardia, hypotensionGI: nausea, vomiting, cramping, diarrhea

  • Type I: Atopia Allergy prone individualsGenetic predispositionMore IgEMore mast cell receptors for antibodies than normal

  • Type I: AnaphylaxisSevere, generalized Type I reactionLife-threateningLoss of airwayVentilatory failureHypoperfusion

  • Type IITissue specificReaction to tissue-specific antigensCauses target cell destruction, dysfunctionExogenous or endogenous antigen

  • Type IIMost commonly affected cellsRed blood cellsThyroid cells

  • Type II: MechanismsAntibody binds to cell membrane, triggers compliment-mediated lysisExamplesReaction to transfused bloodHemolytic disease of newborn

  • Type II: MechanismsAntibodies promote target cell clearance by macrophages

  • Type II: MechanismsAntibodies bind to target cells and cytotoxic T-cellsTrigger release of toxins to destroy target cells

  • Type II: MechanismsAntibody binds to cell membrane, causes alterations in target cell function Example: Graves' diseaseAntibody binds to thyroid cell membraneMimics Thyroid Stimulating Hormone actionCauses production of excessive amounts of thyroid hormoneResults in common form of hyperthyroidism

  • Type III Mediated by antigen/ antibody complex deposition in tissuesExogenous or endogenous antigen

  • Type III: MechanismAg-Ab complex deposited in tissuesEspecially sensitive tissues are blood vessels, GI, respiratory systemCauses complement activation, increased neutrophil activityNeutrophils have trouble digesting complexes, release lysosomes causing damage

  • Type IIIImmune complex quantity varies over time Symptomatic periods alternate with periods of remission

  • Type III: Serum SicknessRepeated intravenous antigen injectionsImmune complexes deposited in tissues Fever, rash, pain, lymphadenopathy

  • Type III: Raynauds PhenomenonTemperature governs immune complex deposition in peripheral circulationExposure to cold causes redness, pain of fingers, toes followed by numbness, cyanosis, gangrene

  • Type III: Arthus Reaction Occurs after repeated LOCAL exposure to exogenous antigenImmune complexes in vessel wallsExamplesCeliac disease from wheat proteinHemorrhagic alveolitis from moldy hay inhalation

  • Type IVDelayedMediated by Td (lymphokine-producing) or Tc (cytotoxic) cellsNo antibody involved

  • Type IVExamplesGraft rejectionContact allergic reactions (poison ivy)

  • Hypersensitivity TargetsAllerginsPollen (hay fever)Drug reactionsFoods

  • Hypersensitivity TargetsNeoantigensHapten binds to protein moleculeChanges its antigenicityCauses it to become an allergen

  • Hypersensitivity TargetsAutoantigensSequestered cells (cornea, testes)Foreign antigen triggered (infection)Suppressor T-cell malfunctionGenetic causes

  • Hypersensitivity TargetsIsoantigensTissue grafts, transplantsRh negative sensitivity

  • Autoimmune DiseaseClinical disorder produced by immune response to normal tissue component of patients body

  • Graves DiseaseAntibody stimulates thyroid hormone over productionProduces hyperthyroidismAntibody, disease can be passed through placenta

  • Rheumatoid ArthritisAntibody reaction to collagen in jointsCauses inflammation, destruction of joints

  • Myasthenia GravisAntibodies destroy acetylcholine receptors on skeletal muscleProduce episodes of severe weaknessAntibodies can cross placenta, affect newborn

  • Immune Thrombocytopenic PurpuraAntibodies destroy plateletsProduces clotting disorders, hemorrhagingAntibodies can cross placenta, affect newborn

  • Isoimmune NeutropeniaAntibodies attack, destroy neutrophilsCan cross placenta, affect newborn

  • Other Autoimmune DiseasesType I diabetes mellitusPrimary myxedemaRheumatic feverCrohns diseaseUlcerative colitisSystemic Lupus Erythematosis (SLE)

  • SLEChronic, multi-system auto-immune diseaseHighest incidence Women, 20-40 years of ageBlack, Hispanic womenMortality after diagnosis averages 5% per year

  • SLEAntibody against nucleic acid components (ANA, anti-nuclear antibody)Immune complex precipitates in tissues, causes widespread destructionEspecially affected are renal system, blood vessels, heart

  • SLESigns/SymptomsFacial rash/skin rash triggered by sunlight exposureOral/nasopharyngeal ulcersFeverArthritis

  • SLESigns/SymptomsSerositis (pleurisy, pericarditis)Renal injury/failureCNS involvement with seizures/psychosisPeripheral vasculitis/gangreneHemolytic anemia

  • SLEChronic managementAnti-inflammatory drugsAspirinIbuprofenCorticosteroidsAvoidance of emotional stress, physical fatigue, excessive sun exposure

  • Disorders of ImmunityImmunodeficiency Diseases

  • Immunodeficiency DiseasePatient unable to fight off infectionHallmarksRepeated infectionsOpportunistic infections

  • Immunodeficiency DiseaseMost are defects in T cells or B cellsT cells, macrophage defects = fungal, viral infectionsB cells, complement defects = bacterial infections

  • Immunodeficiency DiseaseCongenitalAcquired

  • CongenitalB-cell DeficiencyIgA DeficiencyDiGeorges SyndromeSevere Combined Immunodeficiency

  • B Cell DeficiencyAgammaglobulinemiaHypogammaglobulinemia

  • IgA DeficiencyMost common immune deficiency disorderGenetic conditionFailure of IgA synthesisPatient has repeated, recurrent sinus, lung, GI infections

  • DiGeorges SyndromeThymic hypoplasiaSevere decrease in T-cell production, functionDefects of face, ears, heart

  • Severe Combined ImmunodeficiencyThymus development arrested at ~6-8 weeks gestation.Deficiency, defective maturation of stem cells that produce B and T cellsLittle to no antibody production

  • SCIDTwo typesAutosomal recessiveX-linked disease recessive

  • SCIDRecurrent, frequently overwhelming infectionsParticularly respiratory, gastrointestinalMost die in first few years of life, usually by one year of age Death usually due to opportunistic infection

  • AcquiredNutritional deficiencyIatrogenic (drugs, radiation)Trauma (prolonged hypoperfusion)StressInfection (HIV)

  • Immune Deficiency TherapiesB-cell deficiency: Gamma globulinSCID: Bone marrow transplants, enzyme replacementDiGeorges Syndrome: Fetal thymus transplantsGene therapy