Pathology

DISEASESOFIMMUNITY

1. 5.1Generalfeaturesoftheimmunesystem2. 5.2Hypersensitivityreactions3. 5.3Immunologictoleranceandcausativemechanismsofautoimmunedisease4. 5.4Acquiredimmunodeficiencysyndrome(AIDS)

Whatisthedifferencebetweeninnateandadaptiveimmunity?Innateimmunity(alsocallednatural,ornative,immunity)referstothemechanismsthatarereadytoreacttoinfectionsevenbeforetheyoccur,andthathaveevolvedtospecificallyrecognizeandcombatmicrobes.Adaptiveimmunity(alsocalledacquired,orspecific,immunity)consistsofmechanismsthatarestimulatedby(“adaptto”)microbesandarecapableofrecognizingmicrobialandnonmicrobialsubstances.

Whatishumoralandcellmediatedimmunity?Therearetwotypesofadaptiveimmunity:humoralimmunity,whichprotectsagainstextracellularmicrobesandtheirtoxins,andcell-mediated(orcellular)immu-nity,whichisresponsiblefordefenseagainstintracellularmicrobes.HumoralimmunityismediatedbyB(bonemarrow–derived)lymphocytesandtheirsecretedproducts,antibodies(alsocalledimmunoglobulins,Ig),andcellularimmunityismediatedbyT(thymus-derived)lymphocytes.Bothclassesoflymphocytesexpresshighlyspecificreceptorsorawidevarietyofsubstances,whicharecalledantigens.WhatisType1hypersensitivityreaction?Thesearealsocalledallergicreactions,orallergies.Theyareinducedbyenvironmentalantigens (allergens) that stimulate strong TH2 responses and IgE production in genetically susceptible individuals. IgE coats mast cells by binding to Fcε receptors; reexposure to the allergen leads to cross-linking of the IgE and FcεRI, activation of mast cells, and release of mediators. The principal mediators are histamine, proteases, and other granule contents, prostaglandins and΄leukotrienes, and cytokines. The mediators are responsible for the immediate vascular and smooth muscle reactions and the late-phase reaction (inflammation). The clinical manifestations may be local or systemic, and range from mildly annoying rhinitis to fatal anaphylaxis.

WhatisType2hypersensitivityreaction?Inantibody-mediateddisorders(typeIIhypersensitivity),secretedIgGandIgMantibodiesinjurecellsbypromotingtheirphagocytosisorlysisandinjuretissuesbyinducinginflammation.Antibodiesmayalsointerferewithcellularfunctionsandcausediseasewithouttissueinjury.

WhatisType3hypersensitivity?Inimmunecomplex–mediateddisorders(typeIIIhypersensitivity),IgGandIgMantibodiesbindanti-gensusuallyinthecirculation,andtheantigen-antibodycomplexesdepositintissuesandinduceinflammation.Theleukocytesthatarerecruited(neutrophilsandmono-cytes)producetissuedamagebyreleaseoflysosomalenzymesandgenerationoftoxicfreeradicals.WhatisType4hypersensitivity?Incell-mediatedimmunedisorders(typeIVhypersensitivity),sensitizedTlymphocytes(TH1andTH17cellsandCTLs)arethecauseofthetissueinjury.TH2cellsinducelesionsthatarepartofimmediatehypersensitivityreactionsandarenotconsideredaformoftypeIVhypersensitivity.

Whatisthepathogenesisofautoimmunedisease?Autoimmunityarisesfromacombinationoftheinheritanceofsusceptibilitygenes,whichmaycontributetothebreakdownofself-tolerance,andenvironmentaltriggers,suchasinfectionsandtissuedamage,whichpromotetheactivationofself-reactivelymphocytes.

WhatisSLE(systemiclupuserythematosis)?SLEisanautoimmunediseaseinvolvingmultipleorgans,characterizedbyavastarrayofautoantibodies,particularlyantinuclearantibodies(ANAs),inwhichinjuryiscausedmainlybydepositionofimmunecomplexesandbindingofantibodiestovariouscellsandtissues.Thediseasemaybeacuteorinsidiousinitsonset,andistypicallyachronic,remittingandrelapsing,oftenfebrile,illness.Injurytotheskin,joints,kidney,andserosalmembranesisprominent.Virtuallyeveryotherorganinthebody,however,mayalsobeaffected.WhatisSjogren’ssyndrome?Sjögrensyndromeisachronicdiseasecharacterizedbydryeyes(keratoconjunctivitissicca)anddrymouth(xerostomia)resultingfromimmunologicallymediateddestructionofthelacrimalandsalivaryglands.Itoccursasanisolateddisorder(primaryform),alsoknownasthesiccasyndrome,ormoreofteninassociationwithanotherautoimmunedisease(secondaryform).Amongtheassociateddisorders,rheumatoidarthritisisthemostcommon,butsomepatientshaveSLE,polymyositis,scleroderma,vasculitis,mixedconnectivetissuedisease,orthyroiditis.Whatissystemicsclerosis?Systemicsclerosisischaracterizedby:(1)chronicinflammationthoughttobetheresultofautoimmunity(2)widespreaddamagetosmallbloodvessels(3)progressiveinterstitialandperivascularfibrosisintheskinandmultipleorgans.Althoughthetermsclerodermaisingrainedinclinicalmedicine,thisdiseaseisbetternamedsystemicsclerosisbecauseitischaracterizedbyexcessivefibrosisthroughoutthebody.Theskinismostcommonlyaffected,butthegastrointestinaltract,kidneys,heart,muscles,andlungsalsoarefrequentlyinvolved.Insomepatientsthediseaseseemstoremainconfinedtotheskinformanyyears,butinthemajorityitprogressestovisceralinvolvementwithdeathfromrenalfailure,cardiacfailure,pulmonaryinsufficiency,orintestinalmalabsorption.

WhatisAcquiredImmuneDeficiencySyndrome?AIDSisadiseasecausedbytheretrovirushumanimmunodeficiencyvirus(HIV)andcharacterizedbyprofoundimmunosuppressionthatleadstoopportunisticinfections,secondaryneoplasms,andneurologicmanifestations.

ThelifecycleofHIVconsistsofinfectionofcells,integrationoftheprovirusintothehostcellgenome,activationofviralreplication,andproductionandreleaseofinfectiousvirus.HIVinfectscellsbyusingtheCD4moleculeasreceptorandvariouschemokinereceptorsascoreceptors.