ÿWPCð   £œ}›¯ÍiØ_š¤ÍN‡;}äµuc¶z"°›»â¢Ã[Í‘m°Ÿý ÅtÙ‰à†«Þ]·éb’\¬–݃7˜UÊõ«>œ*Ä çË1x ò) = ›OÉí¹%"Ùn?g aTD“?s;GÆ»ÏÇE`€7É ;üÝ7¤ÑèˆoT1Ï[éÄj–*X‡¶_¸á`M:뢡Š¥ '…Yh¦´¾ãáÿh±<õÑH„8 ›ùýv ­— ¶þ>Dþ©Œ¢À–wIGÈpT/[ek%€¢ðäcÄ”z=Z(ü—Áâ¦Eì'}ª·'U?ZÒ¤£áÔâ2¨5Ì·(þGO@Í+A ¡¹,Í Yäá‘òúÓQkf}P`ŸO©xJÃÄ¿TÏŸTÆæ³hl ûÝ\à0Á! XÉÑæ˜Z ¦‡Ü‚«‹tOÍX‡p#利Ë˯Óóf±ÁÒsîžÒ'~N`Št¬"ÀM©eoMuV0<¬Í•íþ#%T~z±”½ÇÉDDíBîdÖ~)OÈc}Qu¡Zƒr±$ŒD'%A6D^¡"£p“Xåã2-ˆ?ŒœÙc+¡óì/x>† ö;[ƒ1¬@‘nÐ>M˱=b'U6" %X€^Þn­îN› 0(U:ÅU4ÿw347UNK 0D™ 0UÝ2 ˜4 UBÌ E m ' Æ/ 0eõ  ÆZ 0 g  ‡#É^ VU@b 1‡¢ 72) 1u[ 72ÐU> 0"c@ B£ 0 wÀ 1‡7 72¾<ô\  `(Roman 10cpiX' É3. ImmunologyLecture  0 .   3|x«<ô\  `(Roman 10cpiXÂxô\  @Ž”×õ X@($¡¡,@ ÐAZ‹"Arial RegulargArial Bolda‡1(ÖÃ9 Z ‹6Times New Roman Regular(3¯$©©Ý ƒ!ÝÝ  Ý>ÿÿ$"Small Circleð"ðà0..à ŽÝ ƒ ¯)ÝÝ  ÝÔ_ÔÒ„°ÒÒ„°ÒßA€#) °°xdE„WÐ AßÐ X ÐÔ‡ Xp3XXXÔÔ€ &þÈ%X Xp3ÔIII.€€Immunology€Review€à€ZZ?T$àÔ‡ ô‹ò% &þÈÔÔ#†ôp3Xò ô‹#ÔÔ‡ôÞòXôp3ÔMLAB€2431€Ô#†&óP%òôÞ#ÔÔ‡Xò³X%&óPÔÔ#†Xp3XXXò³G#ÔÔ‡!Xp3XXXp3ÔÝ ƒÿÿÿÝð"ðà0@..àÝ  ÝÔ#†!&p3XX!Xp3“#ÔÔ‡!ôp3XX!&p3ÔÔ#†ôp3XX!ôp3Õ#ÔÔ‡ôÞòXôp3ÔÔ#†ôp3XòôÞ‹#ÔÔ‡ôÞòXôp3ÔÔ#†&óP%òôÞI#ÔÔ‡ôÞò%&óPÔÚ  Ú17Ú  Ú€Ô#†&óP%òôÞ#ÔÔ#†&p3X%&óPÍ#Ô,§Öh Z*Helvetica RegularÿU‹ÿÀÀÀ 1, 2, 3,Level 1Level 2Level 3Level 4Level 54#,f2Quick 1.ÚƒÚÚ  Ú.à0 àÛ€Ûa, b, c,Level 1Level 2Level 3Level 4Level 56#,ö4Quick a. ÚƒÚÚ  Ú.à0 àÛ€ÛH˜hp LaserJet 1300 PCL 5eÈÈ,,,,ÈÈ0œˆ1é (ÌÆC Z‹(Times New Roman (5hCEKQW]cioAutoList1a.a.a.a.a.a.a.a.a.3#37=CIQYag­­1.a.i.(1)(a)(i)1)a)i)<ô\  `(&Roman 10cpi12pt(;3£$´´Ô2#ÔÚ  Ú0Ú  Ú.Ô3  Ôà0  à d(Oé;$µµà0  àÔ2#ÔÚ  ÚaÚ  Ú.Ô3  Ôà0` (#(#à(EhCEKQW]cioAutoList2a.a.a.a.a.a.a.a.%a.Ý ƒ!ÝÝ  ÝÔ_ÔÑX°ÑÒH°ÒÒ„°ÒÑX°ÑØØò òÔ€XIàXXXÔÓ  ÓÓ  ÓÖ€ÿÿÖÑAÈÑÔ‡Xp3XXXIàÔÑ8€ â” XXdìdÈ8ÑIII.€€Immunology€ReviewÔ#†XIàXXXp3Ñ#Ôó óÐ X ÐÓ¢ÓÌÔ€&x• %XXIàÔÔ€&þÈ% %&x•ÔA.à0   àImmunologic€Response€Serves€Three€FunctionsÐ*Ò T$ T$ ÐÌà0   à1.à0ø T$ T$àò òDefenseó 󀄀immunologically€mediated€resistance€to€infection.ÐÚ‚øT$øT$ ÐÌà   à2.à0 ø àò òHomeostasisó 󀄀that€function€of€the€immune€system€which€removes€effete€or€damaged€self€componentsÐ Ž6 Ðsuch€as€aged€red€cells.ÐjøT$øT$ ÐÌà0   à3.à0ø T$ T$àò òSurveillanceó 󀄀that€function€of€the€immune€system€which€detects€and€destroys€mutant€cells,€thusÐ    Ðproviding€protection€from€malignancy.Ðö ž øT$øT$ ÐÌB.à0   àComponents€of€the€Immune€SystemЦ N  T$ T$ ÐÌà   à1.à0 ø àCells€and€tissues€of€the€immune€system.ÐVþ øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àConsists€of€a€number€of€organs€and€different€cells€types€that€have€evolved€to€recognize€non„Ð ®  Ðself€antigens.ÐÞ†P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àÔ_ÔPluripotentialÔ_Ô€cells€are€capable€of€differentiation€into€many€different€cell€types.ÐŽ6P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àStem€cells€are€located€within€the€bone€marrow,€fetal€liver€and€yolk€sac€of€the€fetus€and€giveÐ >æ Ðrise€to€both€inflammatory€and€immune€cell€lines.оP T$P T$ ÐÌà   àà ø àd.à0 P àThese€self€replicating€cells€differentiate€into€two€types€of€"committed"€stem€cells.ÐÆnP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àOne€group€eventually€differentiates€further€and€matures€to€become€platelets,Ð v Ðerythrocytes€(red€blood€cells),€monocytes€or€Ô_ÔgranulocytesÔ_Ô.ÐNö¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àSecond€group€produces€cells€of€the€ò òlymphoid€lineó ó€only.Ð&Ψ T$¨ T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àCells€of€the€immune€system€are€found€within€the€blood,€body€tissues,€thymus,€spleen,€liver,Ð Ú‚ Ðlymph€nodes€and€those€body€areas€exposed€to€the€external€environment.вZP T$P T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àThese€organs€comprise€the€Ô_ÔreticuloendothelialÔ_Ô€system€(RES).Ðb !P T$P T$ ÐÌà0   à2.à0ø T$ T$àMonocyte„Macrophage€Cell€SystemÐ º#øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àDerived€from€stem€cell€in€the€bone€marrow.ÐÂ!j%P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àMonocytes€circulate€to€sites€of€inflammation€or€migrate€to€various€tissues.Ðr#!'P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àMay€leave€the€blood€for€the€tissues€and€will€further€differentiate€into€tissueÐ "%Ê") ÐÔ_ÔmacrophagesÔ_Ô.Ðú%¢#*¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àTissue€Ô_ÔmacrophagesÔ_Ô€found€throughout€the€body,€especially€in€the€liver,€spleen,Ð ª'R%, Ðperitoneal,€pleural€and€Ô_ÔsynovialÔ_Ô€fluids€and€in€lymph€nodes,€tonsils€and€gut„associatedÐ ‚(*&- Ðlymphoid€tissues.ÐZ)'.¨ T$¨ T$ ÐÌÌÌÌÌÐ j.,4 Ðà0   àà0ø T$ T$àc.à0P øT$øT$àÔ_ÔMacrophagesÔ_Ô€have€several€cell€surface€receptors,€one€of€them€being€a€receptor€for€the€FcÐ X Ðportion€of€the€immunoglobulin€molecule.Ð0ØP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àCells€coated€with€immunoglobulin€can€attach€to€Ô_ÔmacrophagesÔ_Ô€when€it€come€inÐ àˆ Ðcontact€with€Fc€receptor.и`¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àThis€allows€removal€of€many€cells€from€the€circulation€by€Ô_ÔmacrophagesÔ_Ô.Ðh¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àThe€ability€of€Ô_ÔmacrophagesÔ_Ô€to€remove€antibody€coated€cells€(ò òmacrophageÐ  À Ðclearanceó ó)€varies€in€intensity.Ðô œ ¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àTissue€Ô_ÔmacrophagesÔ_Ô€also€possess€a€receptor€for€the€complement€component€C3b.Ш P P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àCells€coated€with€complement€may€also€be€removed€from€circulation.ÐX ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àSome€blood€group€antibodies€are€capable€of€complement€activation,€resulting€inÐ 0Ø  Ðcoating€then€destruction€by€Ô_ÔmacrophagesÔ_Ô.а ¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àTissue€Ô_ÔmacrophagesÔ_Ô€also€posses€cell€surface€proteins€of€the€major€Ô_ÔhistocompatibilityÔ_Ô€complexÐ ¸` Ð(Ô_ÔMHCÔ_Ô)€which€is€important€in€transplantation€immunity€and€presentation€of€antigen€to€helperÐ 8 ÐT€lymphocytes.ÐhP T$P T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àÔ_ÔMacrophagesÔ_Ô€participate€in€phagocytosis,€inflammation,€and€cellular€immunity.ÐÀP T$P T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àÔ_ÔMacrophagesÔ_Ô€are€mainly€involved€in€nonspecific€immunity€and€include€the€ò òphagocytic€cellsó ó:€Ð Èp Ðmononuclear€phagocytes,€Ô_ÔpolymorphonuclearÔ_Ô€phagocytes€(neutrophils),€Ô_ÔeosinophilsÔ_Ô€andÐ ¤L Ðò òmediator€cellsó ó:€€Ô_ÔbasophilsÔ_Ô,€mast€cells€and€platelets.Ð|$P T$P T$ ÐÌà0   à3.à0ø T$ T$àT€Lymphocytes€(T€cells)Ð0ØøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àDerived€from€stem€cells€in€the€bone€marrow.ÐàˆP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àPrecursor€cell€leaves€bone€marrow€and€travel€to€the€thymus€to€mature€prior€to€release€intoÐ 8 Ðcirculation.Ðh P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àApproximately€75€to€80%€of€lymphocytes€are€T€cells.ÐÀ"P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àT€lymphocytes€are€important€in€recognizing€foreign€material€that€is€fixed€in€the€tissues€ofÐ È p$ Ðcells.Р!H%P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àThey€are€not€capable€of€secreting€antibody.Ðx" &¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àExamples€of€foreign€materials€are€transplanted€tissue,€tumors€and€organisms€causingÐ P#ø ' Ðtuberculosis.Ð($Ð!(¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àWhen€stimulated€T€cells€differentiate€further€into€several€types€of€T€cells€with€veryÐ %¨") Ðdifferent€functions.€€(These€will€be€covered€in€detail€later).ò òÐØ%€#*¨ T$¨ T$ ÐÌó óà0   àà0ø T$ T$àe.à0P øT$øT$àT€cells€play€an€important€role€in€regulating€the€production€of€antibodies€by€B€cells.€T€„€B€cellÐ ˆ'0%, Ðcooperation€is€necessary€for€antibody€production€to€take€place.Ð`(&-P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)ò òà0¨ P T$P T$àHelper€T€celló 󀄀upon€interaction€with€an€antigenic€molecule€release€substancesÐ *¸'/ Ðwhich€help€B€lymphocytes€to€produce€antibodies€against€this€antigen.Ðì*”(0¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àò òSuppressor€T€celló ó€are€thought€to€"turn€off"€B€cells€so€that€they€can€no€longerÐ œ,D*2 Ðcooperate€with€normal€T€cells€to€induce€an€immune€response.Ðx- +3¨ T$¨ T$ ÐÐ P.ø+4 Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àNormal€immune€response€probably€represents€a€very€fine€balance€between€the€actionÐ X Ðofò ò€helper€ó óand€ò òsuppressoró ó€T€cells.€à0`¨ T$¨ T$àÐ0Ø`T$`T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àò òKiller€ó óorò ò€Killer€T€cellsó ó€precise€identity€and€site€of€origin€are€unknown,€but€they€are€involvedÐ äŒ Ðin€cell€mediated€immunity€by€recognizing€and€destroying€antibody„coated€target€cells.ÐÀhP T$P T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àT€cells€have€surface€proteins€known€as€cluster€determinants€(CDs).ÐpP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àCD4€and€CD8€are€widely€used€in€clinical€medicine.РȨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àHelper€T€cells€are€CD4€positive€cells€enhance€and€promote€the€action€of€otherÐ ø    Ðimmune€cells.ÐÐ x ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àSuppressor€T€cells€are€CD8€positive€and€have€suppressive€or€cytotoxic€effects.Ш P ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àApproximately€65%€of€T€cells€are€helper,€and€35%€are€suppressor€giving€a€ration€ofÐ € (  Ðapproximately€2:1.ÐX ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à5)à0¨ P T$P T$àSubset€analysis€of€the€CD4:CD8€ratio€is€useful€in€following€the€course€of€AIDS.Ð0Ø ¨ T$¨ T$ ÐÌà0   à4.à0ø T$ T$àB€lymphocytes€(B€cells)Ðàˆ øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àDerived€from€stem€cells€in€the€bone€marrow.Ð8P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àName€comes€from€discovery€of€these€stem€cells€in€the€Bursa€of€Ô_ÔFabricusÔ_Ô€in€theÐ h Ðchicken.Ð@è¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àIn€humans€development€occurs€in€the€bone€marrow.ÐÀ¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àB€lymphocytes€are€concerned€with€humoral€immunity,€i.e.€they€recognize€certain€substancesÐ Èp Ðas€foreign.РHP T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àTransform€into€plasma€cells€and€produce€a€family€of€proteins€known€as€antibodiesÐ x  Ðor€immunoglobulins.ÐPø¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àImportant€in€the€eradication€of€circulating€€foreign€material€such€as€bacteria.Ð(Ш T$¨ T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àActivated€B€cells€begin€antibody€production€and€undergo€a€process€called€Ô_ÔclonalÔ_Ô€expansion.ÐØ€P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àInvolves€commitment€of€B€cell€to€production€of€an€antibody€with€a€singleаX¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$àà0¨ P T$P T$àspecificity€with€proliferation€of€that€particular€cell€line.Ј0¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àThis€process€generates€many€B€cell€committed€to€production€of€the€same€antibody.Ð` ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àMemory€B€cells€are€generated,€resulting€in€a€rapid€production€of€antibody.Ð8à!¨ T$¨ T$ ÐÌC.à0   àImmune€Response€Ðè# T$ T$ ÐÌà0   à1.à0ø T$ T$àConsists€of€two€types:И!@%øT$øT$ Ðà0   àà0ø T$ T$àa.à0P øT$øT$àInnate€or€nonspecific€immune€response.Ðp" &P T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àAdaptive€or€specific€immune€response.ÐH#ð 'P T$P T$ ÐÌà0   à2.à0ø T$ T$àInnate€immunity€involves€the€bodyððs€òòfirst€line€of€defenseóó.à0¸øT$øT$àà0¸T$¸T$àà0hT$T$àÐø$ ")hT$hT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àPhysical€barriers€which€include€intact€skin€and€mucous€membranes.Ш&P$+P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àPhysiological€factors€which€include€hydrochloric€acid€in€the€stomach,€ciliated€epitheliumÐ X(&- Ðlining€the€respiratory€tract,€flushing€action€of€urine,€large€amounts€of€unsaturated€fatty€acidsÐ 0)Ø&. Ðfound€in€the€skin,€sweat,€tears,€and€commensal€normal€flora.Ð*°'/P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àIf€an€organism€penetrates€through€these€defense€mechanisms€it€encounters€phagocytic€cellsÐ ¸+`)1 Ðof€the€RES€which€will€engulf€and€destroy€them.Ð,8*2P T$P T$ ÐÌÌÐ /À,5 Ðà0   àà0ø T$ T$àd.à0P øT$øT$àòòInflammationóó€is€the€body's€reaction€to€injury€and€is€known€as€the€body's€second€line€ofÐ X Ðdefense€which€results€in:Ð0ØP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àIncreased€blood€supply€to€the€area.Ðàˆ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àIncreased€capillary€permeability.и`¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àMigration€of€leukocytes€into€the€surrounding€tissue.Ð8¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àThese€three€events€manifest€symptoms€which€include€pain,€heat,€redness€andÐ h Ðswelling.Ð@è¨ T$¨ T$ ÐÌà0   à3.à0ø T$ T$àAdaptive€(specific)€immunity€involves€specificity,€recognition,€memory€and€specific€reactivity.Ðð ˜ øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àInvolves€ability€to€recognize€self€and€non„self.Р H P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àEncounters€with€non„self€or€foreign€materials€results€in€production€of€antibodies€(humoralÐ P ø  Ðimmunity)€or€actions€of€T„cells€(cell€mediated€immunity).Ð(Ð P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àGreat€deal€of€interaction€exists€between€these€two€systems.ÐØ€ P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àÔ_ÔImmunohematologyÔ_Ô€primarily€concerned€with€the€causes€and€effects€of€humoral€immunity.Ј0P T$P T$ ÐÌD.à0   àAntigensÐ8à T$ T$ ÐÌà0   à1.à0ø T$ T$àAn€antigen€is€any€substance€which€is€recognized€as€foreign€by€the€body€and€is€capable,€underÐ è Ðappropriate€conditions,€of€provoking€a€specific€immune€response.€€It€is€capable€of:ÐÀhøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àStimulating€the€formation€of€antibody€and€the€development€of€cell„mediated€immunity.ÐpP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àReacting€specifically€with€the€antibodies€or€T€lymphocytes€produced.Ð ÈP T$P T$ ÐÌà0   à2.à0ø T$ T$àPhysical€nature€of€antigensÐÐxøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àò òForeign€natureó 󀄀The€body€is€tolerant€of€its€own€components€and€does€not€initiate€immuneÐ €( Ðresponse€against€these.Ð\ P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àò òMolecular€sizeó 󀄀molecules€with€a€molecular€weight€of€less€than€10,000€Ô_ÔdaltonsÔ_Ô€have€no€orÐ  ´" Ðweak€antigenicity.Ðè#P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àò òMolecular€complexity€and€rigidityó 󀄀Complex€proteins€are€better€antigen€than€largeÐ ˜!@% Ðrepeating€polymers€such€as€lipids,€carbohydrates,€and€nucleic€acids,€which€are€relatively€poorÐ t" & Ðantigens.ÐL#ô 'P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àò òGenetic€factorsó 󀄀not€all€individuals€within€a€species€will€show€the€same€response€to€aÐ ü$¤") Ðsubstance€„€some€are€ò òrespondersó ó€and€some€ò ònon„respondersó ó.ÐØ%€#*P T$P T$ Ѐ€Ð ´&\$+ Ðà0   àà0ø T$ T$àe.à0P øT$øT$àò òRoute€of€administration€and€doseó ó€(oral,€skin,€intramuscular,€etc.)€for€stimulation€of€theÐ Œ'4%, Ðimmune€response€is€very€important€and€recognition€may€not€occur€if€dose€is€too€large€or€tooÐ h(&- Ðsmall.Ð@)è&.P T$P T$ ÐÌà0   à3.à0ø T$ T$àAntigenic€Determinants€or€Ô_ÔepitopesÔ_ÔÐð*˜(0øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àStructures€on€antigens€that€are€recognized€as€foreign€by€the€immune€system.Р,H*2P T$P T$ ÐÌÐ P.ø+4 Ðà0   àà0ø T$ T$àb.à0P øT$øT$àNumber€of€antigenic€determinants€on€a€molecule€varies€with€molecular€size.€ÐXP T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àAn€immune€response€is€directed€against€specific€determinants,€and€resultant€antibodies€willÐ ° Ðspecifically€bind€to€them.ÐàˆP T$P T$ Ðà   àÌÌà0   àà0ø T$ T$àd.à0P øT$øT$àMultivalent€antigens€may€elicit€antibodies€of€different€Ô_ÔspecificitiesÔ_Ô,€each€directed€to€aÐ h Ðdifferent€Ô_ÔepitopeÔ_Ô.Ð@èP T$P T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àSome€antibodies€produced€in€response€to€one€antigen€may€cross€react€with€other€antigensÐ ð ˜  Ðhaving€the€common€determinant.ÐÈ p P T$P T$ ÐÌà0   à4.à0ø T$ T$àBlood€group€antigens€are€chemical€structures€embedded€in€or€protruding€from€Ô_ÔRBCsÔ_Ô,€Ô_ÔWBCsÔ_Ô,€andÐ x  Ðplatelets€and€have€three€common€forms:ÐP ø øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àÔ_ÔGlycoproteinsÔ_Ô€„€Ô_ÔHLAÔ_Ô€system.Ш P T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àÔ_ÔGlycolipidsÔ_Ô€„€Ô_ÔABHÔ_Ô,€Lewis,€Ii,€and€P€blood€group€systems.ÐØ€ P T$P T$ Ðà0   àà0ø T$ T$àc.à0P øT$øT$àProteins€„€Rh,€M,€N€blood€group€systems.аXP T$P T$ ÐÌà0   à5.à0ø T$ T$àAntigens€classified€into€two€major€types:Ð`øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àexogenous,€outsideиP T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àendogenous,€insideÐèP T$P T$ ÐÌà0   à6.à0ø T$ T$àBlood€bankers€concerned€with€Ô_ÔallogeneicÔ_Ô€antigens€(from€other€humans)€and€autologous€(self)Ð ˜@ Ðantigens.ÐpøT$øT$ ÐÌà0   à7.à0ø T$ T$àÔ_Ôòòò òHaptensÔ_Ô€ó óóóare€substances,€usually€of€low€molecular€weight,€that€can€combine€with€antibody€but€cannotÐ  È Ðinitiate€an€immune€response€unless€it€is€coupled€to€a€larger€carrier€molecule.€€Ðú¢øT$øT$ ÐÌE.à0   àCellular€Immunity€or€cell€mediated€immunity€ÐªR T$ T$ ÐÌà0   à1.à0ø T$ T$àImportant€defense€mechanism€against€viral€infections,€some€fungal€infections,€parasitic€disease€andÐ Z  Ðagainst€some€bacteria,€particularly€those€inside€cells.Ð2Ú!øT$øT$ ÐÌà0   à2.à0ø T$ T$àResponsible€for€delayed€hypersensitivity,€transplant€rejection€and€possibly€tumor€surveillance.ÐâŠ#øT$øT$ ÐÌà0   à3.à0ø T$ T$àThis€branch€of€the€immune€system€depends€on€the€presence€of€thymus„derived€lymphocytes€(TÐ ’!:% Ðlymphocytes).Ðj" &øT$øT$ ÐÌà0   à4.à0ø T$ T$àCell„mediated€reaction€is€initiated€by€the€binding€of€the€antigen€with€an€antigen€receptor€on€theÐ $Â!( Ðsurface€of€the€sensitized€T€lymphocyte,€causes€stimulation€of€the€T€lymphocyte€helper€and€suppressorÐ ò$š") ÐT€cells€that€regulate€the€intensity€of€the€body's€immune€response.ÐÊ%r#*øT$øT$ ÐÌà0   à5.à0ø T$ T$àT€cells€capable€of€ò òdirect€interactionó ó€with€the€antigen.€€This€group€can€be€divided€further.Ðz'"%,øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àT€cells€which,€on€contact€with€the€specific€antigen,€liberate€substances€called€ò òlymphokines.ó óÐ.)Ö&.P T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àò òCytotoxic€T€cellsó ó€which€directly€attack€antigen€on€the€surface€of€foreign€cells.Ð *²'/P T$P T$ ÐÌà0   à6.à0ø T$ T$àò òLymphokinesó ó€are€a€mixed€group€of€proteins€which€have€diverse€properties.о+f)1øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àOne€function€is€the€attraction€of€neutrophils€and€monocytes€to€the€site€of€infectionÐr-+3P T$P T$ ÐÌÐ "/Ê,5 Ðà0   àà0ø T$ T$àb.à0P øT$øT$àSome€lymphokines€will€cause€aggregation€of€Ô_ÔmacrophagesÔ_Ô€at€the€site€of€the€infection,€whileÐ X Ðothers€activate€Ô_ÔmacrophagesÔ_Ô,€inducing€them€to€Ô_ÔphagocytoseÔ_Ô€and€destroy€foreign€antigensÐ 0Ø Ðmore€vigorously.аP T$P T$ ÐÌà0   à.à0ø T$ T$àc.à0P øT$øT$àThe€end€result€of€their€combined€action€is€an€òòamplification€óóof€the€local€inflammatory€reactionÐ ¸` Ðwith€recruitment€of€circulating€cells€of€the€immune€system.Ð8P T$P T$ ÐÌF.à0   àThe€Humoral€Immune€ResponseÐ@è T$ T$ ÐÌà0   à1.à0ø T$ T$àHumoral€immunity€has€to€do€with€the€production€of€antibodies€induced€when€the€hosts's€immuneÐ ð ˜  Ðsystem€comes€into€contact€with€foreign€antigenic€substance€and€reacts€to€this€antigenic€stimulation.ÐÈ p øT$øT$ ÐÌà0   à2.à0ø T$ T$àPrimary€and€Secondary€Immune€responsesÐx øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àInvolves€humoral€and€cellular€events,€first€exposure€results€in€ò òòòprimary€immune€responseóóó ó,Ð (Ð  Ðsubsequent€exposures€result€in€ò òòòsecondary€or€anamnestic€responseóó.ó óЪ P T$P T$ ÐÌØ€ØÝ‚,öÿÝÝ  Ýà0   àà0ø T$ T$àÝ‚,ö)_ÝÚƒÚbÚ  Ú.à0P øT$øT$àÝ  ÝThe€immune€response€is€mediated€by€lymphocytes€which€differentiate€in€the€bone€marrowÐ ¶^ Ðinto€B€lymphocytes€or€B€cells.݃,ö)_d_ÝۀیЎ6P T$P T$ ÐŒÝ  ÝÌÝ‚,öÿÝÝ  Ýà0   àà0ø T$ T$àÝ‚,ö•`ÝÚƒÚcÚ  Ú.à0P øT$øT$àÝ  ÝB€cells€produce€antibodies€capable€of€reacting€with€the€antigen€which€caused€theirÐ >æ Ðproduction.݃,ö•`Ð`ÝۀیоP T$P T$ ÐŒÝ  ÝÔ_ÔÔ_ÔÌÝ‚,öÿÝÝ  Ýà0   àà0ø T$ T$àÝ‚,ö bÝÚƒÚdÚ  Ú.à0P øT$øT$àÝ  ÝThe€primary€immune€response€involves€the€first€encounter€with€the€antigen€and€usuallyÐ Æn Ðinvolves€the€cellular€immune€system.݃,ö bFbÝۀیОFP T$P T$ ÐŒÝ  Ýà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àAntigen€is€ingested€by€antigen€processing€cells€(Ô_ÔAPCsÔ_Ô)€and€presented€to€the€helperÐ v ÐT€cell€which€has€a€receptor€for€the€antigen€on€its€surface.ÐNö¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àActivated€helper€T€cell€secretes€lymphokines€which€causes€activation€of€the€B€cells.Ð&Ψ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àB€cells€proliferate€and€differentiate€into€antibody€secreting€cells€(plasma€cells)€andÐ þ¦ Ðmemory€cells.ÐÖ~¨ T$¨ T$ ÐÌÝ‚,öÿÝÝ  Ýà0   àà0ø T$ T$àÝ‚,öFfÝÚƒÚeÚ  Ú.à0P øT$øT$àÝ  ÝThe€secondary€immune€response€involves€a€later€exposure€to€the€same€antigen€causingÐ †. Ðactivation€of€the€memory€cells€to€proliferate€into€plasma€cells€with€immediate€production€ofÐ ^  Ðantibody.݃,öFffÝÛ€ÛŒÐ6Þ!P T$P T$ ÐŒÝ  ÝÌà0   àà0ø T$ T$àf.à0P øT$øT$àAntibody€production€occurs€in€four€phases€following€antigen€challenge:ÐæŽ#P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àLag€phase€when€no€antibody€is€detectable.о f$¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àLog€phase€in€which€antibody€titer€rises€logarithmically.Ж!>%¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àPlateau€phase€during€which€the€antibody€titer€remains€steady.Ðn" &¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àDecline€phase€during€which€antibody€levels€gradually€decline.ÐF#î '¨ T$¨ T$ ÐÌà0   à3.à0ø T$ T$àResponses€following€primary€and€secondary€antigenic€challenge€differ€in€several€major€respects:Ðö$ž")øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àò òTimeó ó.€€Ð¦&N$+P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àPrimary€response€involves€days,€weeks€or€even€months€before€appearance€ofÐ ‚'*%, Ðdetectable€antibody€(long€lag€phase).ÐZ(&-¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àSecondary€response€results€in€rapidly€increased€antibody€levels€detectable€in€a€matterÐ 2)Ú&. Ðof€hours€(short€lag€phase).Ð *²'/¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àò òAntibody€Titeró ó.к+b)1P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àPrimary€response€results€in€generation€of€a€pool€of€potential€antibody„forming€cellsÐ –,>*2 Ðand€initial€low€titer.Ðn-+3¨ T$¨ T$ ÐÌÐ /Æ,5 Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àSecondary€response€plateau€levels€of€antibody€are€much€greater€and€remains€elevatedÐ X Ðlonger.Ð0ب T$¨ T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àò òAntibody€Classó ó.ÐàˆP T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àPrimary€response€initial€antibody€produced€is€IgM,€within€2€to€3€weeks€productionÐ ¼d Ðswitches€to€IgG.Д<¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à€2)à0¨ P T$P T$àSecondary€immune€response€memory€B€cells€immediately€produce€IgG.Ðl¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àò òAntibody€affinity€and€avidity.ó óÐ ÄP T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àAntibodies€in€primary€response€usually€have€low€òòaffinity€óó(degree€of€fit€between€andÐ ø    Ðantigen€and€antibody)€for€respective€antigen€and€lower€òòavidity€óó(strength€of€bondÐ Ð x  Ðbetween€an€antigen€and€its€respective€antibody).Ш P ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àSecondary€response€has€greatly€increased€affinity€and€avidity.Ѐ ( ¨ T$¨ T$ ÐÌG.à0   àImmunoglobulinsÐ0Ø  T$ T$ ÐÌÝ‚,fÿÝÝ  Ýà0   àÝ‚,f uÝÚƒÚ1Ú  Ú.à0ø T$ T$àÝ  ÝIntroduction݃,f u3uÝÛ€ÛŒÐàˆ øT$øT$ ÐŒÝ  Ýà0   àÐ  T$ T$ ÐÓ€ (5h83ÓÝ"‚"3£"ÝÝ  Ýà0   àà0ø T$ T$àÝ‚"3£‹vÝÔ25hÔÚ  ÚaÚ  Ú.Ô3  Ôà0P øT$øT$àÝ  ÝHumans€produce€specific€proteins€or€immunoglobulins€which€can€be€differentiated€on€theÐ 8 Ðbasis€of:݃"3£‹vØvÝŒÐhP T$P T$ ÐŒÝ  Ýà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àSizeÐ@è¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àBiologic€functionÐÀ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àbiochemical€propertiesÐ𘨠T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àserological€activityÐÈp¨ T$¨ T$ ÐÌÝ"‚"3£"ÝÝ  Ýà0   àà0ø T$ T$àÝ‚"3£ÔyÝÔ25hÔÚ  ÚbÚ  Ú.Ô3  Ôà0P øT$øT$àÝ  ÝHuman€immunoglobulins€have€been€assigned€to€five€classes€based€on€the€primary€structureÐ x  Ðof€their€respective€heavy€chains.݃"3£Ôy!zÝŒÐPøP T$P T$ ÐŒÝ  ÝÌà0   à2..à0ø T$ T$àBasic€Structure€of€ImmunoglobulinsШøT$øT$ ÐÌÝ"‚$é;"ÝÝ  Ýà   àÝ‚$é;¸{Ýà0 ø àÔ25hÔÚ  ÚaÚ  Ú.Ô3  Ôà0P øT$øT$àÝ  ÝBasic€Structure€consists€of€two€identical€heavy€chains€and€two€light€chains€held€together€byÐ °X Ða€chemical€link€(disulfide€bonds).݃$é;¸{ñ{݌Ј0P T$P T$ ÐŒÝ  ÝÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àLight€chains€are€named€by€the€Ô_ÔgreekÔ_Ô€letters€ò òkappa€ó óand€ò òlambda.ó óÐ8à!¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àHeavy€chains€by€the€Ô_ÔgreekÔ_Ô€letters:€€ò ògamma€(G),€alpha€(A),€mu€(M),€delta€(D),€andÐ ¼" Ðepsilon€(E).ó óÐð˜#¨ T$¨ T$ ÐÌÝ"‚$é;"ÝÝ  Ýà   àÝ‚$é;Ýà0 ø àÔ25hÔÚ  ÚbÚ  Ú.Ô3  Ôà0P øT$øT$àÝ  ÝAntibodies€are€treated€with€enzymes€to€determine€structure€and€activity€of€the€various€areasÐ  !H% Ðof€the€antibody.݃$é;AÝŒÐx" &P T$P T$ ÐŒÝ  ÝÌÝ"‚$é;"ÝÝ  Ýà   àÝ‚$é;s€Ýà0 ø àÔ25hÔÚ  ÚcÚ  Ú.Ô3  Ôà0P øT$øT$àÝ  ÝPapain€breaks€the€Ô_ÔIgÔ_Ô€into€three€fragments:€€2€Fab,€containing€a€light€chain€and€a€portion€ofÐ ($Ð!( Ðthe€heavy€chain,€and€1€Fc€fragment.݃$é;s€¬€ÝŒÐ%¨")P T$P T$ ÐŒÝ  Ýà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àFab€contains€antigen€binding€site.ÐØ%€#*¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àFc€is€the€region€that€determine€biological€properties€of€the€Ô_ÔIgÔ_Ô.а&X$+¨ T$¨ T$ ÐÌà0   à3.à0ø T$ T$àò òIgMó ó€ò òClassó óÐ`(&-øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àLargest€of€all€the€antibody€molecules€and€the€structure€consists€of€five€of€the€basic€unitsÐ *¼'/ Ð(ò òÔ_ÔpentamerÔ_Ôó ó)€joined€together€by€a€structure€known€as€ò òJ„chainó ó.Ðì*”(0P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àAccounts€for€about€5„10%€of€the€immunoglobulin€pool.Р,H*2P T$P T$ ÐÌÐ P.ø+4 Ðà   àà ø àc.à0 P àIgM€is€restricted€almost€entirely€to€the€Ô_ÔintravascularÔ_Ô€space€due€to€its€large€size.ÐXP T$P T$ ÐÌà   àà ø àd.à0 P àIgM€òòò òfixes€complementó óóó€and€is€much€more€efficient€than€IgG€in€the€activation€of€complementÐ ° Ðand€agglutination.ÐâŠP T$P T$ ÐÌà   àà ø àe.à0 P àIt€is€the€first€antibody€to€be€produced€and€is€of€greatest€importance€in€the€first€few€days€ofÐ ’: Ða€òòò òprimary€immune€responseó óóó€to€an€infecting€organism.€€Thus€it€acts€as€an€effective€first€lineÐ j Ðof€defense€against€bacteria.ÐDìP T$P T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àò òòòIgM€does€not€cross€the€placentaóó.ó óÐô œ P T$P T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àMany€blood€group€antibodies€that€are€capable€of€agglutinating€antigen€positive€Ô_ÔRBCsÔ_ÔÐ ¨ P  Ðsuspended€in€saline€in€tests€performed€at€22€C€are€IgM€causing€visible€agglutination.Ѐ ( P T$P T$ ÐÌà0   àà0ø T$ T$àh.à0P øT$øT$àIgM€antibodies€are€potent€Ô_ÔagglutinatorsÔ_Ô€that€òòactivate€complementóó€very€efficiently.Ð0Ø P T$P T$ ÐÌà0   à4.à0ø T$ T$àò òIgG€Classó óÐàˆ øT$øT$ ÐÌØ! !ØÓ€ %(Eh88ÓÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£Ú‹ÝÔ2EhÔÚ  ÚaÚ  Ú.Ô3  Ôà0 P àÝ  ÝMost€abundant€of€the€immunoglobulins€in€the€plasma€(accounts€for€70€to€80%€of€the€totalÐ ”< Ðimmunoglobulin€pool)€and€because€of€its€very€small€molecular€weight€it€can€diffuse€into€theÐ l Ðinterstitial€fluid.€€Ýƒ"3£Ú‹ŒÝŒÐDìP T$P T$ ÐŒÝ  ÝÌò òó óÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£³ÝÔ2EhÔÚ  ÚbÚ  Ú.Ô3  Ôà0 P àÝ  Ýò òó óConsists€of€one€basic€structural€unit,€i.e.€Y„shaped€molecule€having€2€light€chains€and€2Ð ôœ ÐGamma€heavy€chains.݃"3£³øÝŒÐÌtP T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£ÝÔ2EhÔÚ  ÚcÚ  Ú.Ô3  Ôà0 P àÝ  ÝAntibodies€of€this€class€are€produced€in€response€to€a€wide€variety€of€antigens,€includingÐ |$ Ðbacteria,€viruses€and€RBC€and€WBC€allo„antigens.݃"3£aÝŒÐTüP T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£ÝÔ2EhÔÚ  ÚdÚ  Ú.Ô3  Ôà0 P àÝ  ÝIgG€can€coat€organisms€and€this€enhances€their€phagocytosis€by€neutrophils€andÐ ¬ ÐÔ_ÔmacrophagesÔ_Ô.݃"3£âÝŒÐÜ„P T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£’ÝÔ2EhÔÚ  ÚeÚ  Ú.Ô3  Ôà0 P àÝ  ÝThrough€its€ò òòòability€to€cross€the€placentaóóó ó,€maternal€IgG€provides€the€ò òòòmajor€line€of€defenseóóÐ Œ4 Ðagainst€infection€for€the€first€few€weeks€of€a€baby's€life.ó ó݃"3£’S’ÝŒÐh P T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£²“ÝÔ2EhÔÚ  ÚfÚ  Ú.Ô3  Ôà0 P àÝ  Ýò òIt€is€the€predominant€antibody€produced€in€the€secondary€response.ó ó݃"3£²“÷“ÝŒÐÀ"P T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£Ü”ÝÔ2EhÔÚ  ÚgÚ  Ú.Ô3  Ôà0 P àÝ  ÝThe€serologic€behavior€and€characteristics€of€IgG€antibodies€make€them€one€of€the€mostÐ Ì t$ Ðò òclinically€significantó ó€in€blood€banking.݃"3£Ü”!•݌Ф!L%P T$P T$ ÐŒÝ  ÝÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£W–ÝÔ2EhÔÚ  ÚhÚ  Ú.Ô3  Ôà0 P àÝ  ÝMost€€ò òblood€group€antigensó ó€capable€of€eliciting€an€immune€response€result€in€the€productionÐ X#!' Ðof€IgG€antibodies.݃"3£W–œ–ÝŒÐ4$Ü!(P T$P T$ ÐŒÝ  ÝÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àThese€antibodies€are€detected€by€serologic€test€procedures€based€on€their€ò òbehaviorÐ ä%Œ#* Ðcharacteristicsó ó,€such€as€reactivity€at€37€C,€ò òòòcomplement€activationóóó ó,€indirectÐ À&h$+ Ðagglutination€and€hemolysis.М'D%,¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àMuch€of€routine€blood€banking€involves€serologic€test€procedures€designed€to€detectÐ t(&- Ðand€identify€IgG€antibodies.ÐL)ô&.¨ T$¨ T$ ÐÌÝ"‚"3£"ÝÝ  Ýà   àà ø àÝ‚"3£šÝÔ2EhÔÚ  ÚiÚ  Ú.Ô3  Ôà0 P àÝ  ÝFour€subclasses€which€differ€in€their€heavy€chain€composition€and€in€some€of€theirÐ ü*¤(0 Ðcharacteristics€such€as€biologic€activities.€€IgG1,€IgG2,€IgG3€and€IgG4.݃"3£šSšÝŒÐÔ+|)1P T$P T$ ÐŒÝ  ÝÌÌÐ \.,4 Ðà0   à5.à0ø T$ T$àò òÔ_ÔIgAÔ_Ôó ó€ò òClassó óÐXøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àAs€well€as€being€in€the€plasma,€Ô_ÔIgAÔ_Ô€is€the€ò òmajor€immunoglobulin€of€the€external€secretoryÐ  ´ Ðsystem€and€is€found€in€òòsaliva,€tears,€colostrum€breast€milk€and€in€nasal,€bronchial€andÐ è Ðintestinal€secretions.€óóó óÔ_ÔIgAÔ_Ô€is€present€in€large€quantities€in€colostrum€and€breast€milk€and€canÐ Àh Ðbe€transferred€across€the€gut€mucosa€in€the€neonate€and€plays€an€important€role€in€protectingÐ œD Ðthe€neonate€from€infection.ÐtP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àIt€is€produced€in€high€concentrations€by€lymphoid€tissues€lining€the€gastrointestinal,Ð $ Ì Ðrespiratory€and€genitourinary€tracts.Ðü ¤ P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àIt€plays€an€important€role€in€protection€against€respiratory,€urinary€tract€and€bowel€infectionsÐ ¬ T  Ðand€it€is€probably€also€important€in€preventing€absorption€of€potential€antigens€in€the€foodÐ „ ,  Ðwe€eat.Ð\  P T$P T$ ÐÔ_Ôà   àà ø àà P àà ¨ àà  àà X àà ° àà  àà ` àà ¸ àà  àà h àà À! àÔ_ÔÌà   àà ø àd.à0 P àÔ_ÔIgAÔ_Ô€represents€10€to€15%€of€the€total€circulatory€immunoglobulin€pool.Ð ´ P T$P T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àIn€plasma€Ô_ÔIgAÔ_Ô€may€exist€as€a€single€basic€structural€unit€or€as€two€or€three€basic€units€joinedÐ ¼d Ðtogether.€€Ð”<P T$P T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àThe€Ô_ÔIgAÔ_Ô€present€in€secretions€exists€as€two€basic€units€(a€dimer)€attached€to€another€moleculeÐ Dì Ðknow€as€ò òsecretory€componentó ó.ÐÄP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àThis€substance€is€produced€by€the€cells€lining€the€mucous€membranes.ÐÐx¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àIt€is€thought€to€protect€the€Ô_ÔIgAÔ_Ô€in€secretions€from€destruction€by€digestive€enzymes.ШP¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àh.à0P øT$øT$àò òòòÔ_ÔIgAÔ_Ô€does€not€cross€the€placenta€and€does€not€bind€complement.óóó óÐXP T$P T$ ÐÌà0   àà0ø T$ T$àÔ_ÔiÔ_Ô.à0P øT$øT$àFor€blood€banking,€if€an€individual€is€Ô_ÔIgAÔ_Ô€deficient€they€may€produce€anti„Ô_ÔIgAÔ_Ô€which€canÐ  ´ Ðcause€severe,€life„threatening€anaphylactic€reactions€during€transfusion.€€Once€identifiedÐ äŒ Ðthese€individuals€must€be€transfused€with€blood€and€components€which€lack€Ô_ÔIgAÔ_Ô.мdP T$P T$ ÐÌ6.à0   àò òÔ_ÔIgEÔ_Ôó ó€ò òClassó óÐl  T$ T$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àTrace€plasma€protein€(only€about€0.004%)€in€the€plasma€of€non„parasitized€individuals.Ð È"P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àIt€is€of€major€importance€because€it€mediates€some€types€of€allergic€reactions,€allergies€andÐ Ð x$ Ðanaphylaxis€and€is€generally€responsible€for€an€individual's€immunity€to€invading€parasites.Ш!P%P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àÔ_ÔIgEÔ_Ô€is€unique€in€that€its€Fc€region€binds€strongly€to€a€receptor€on€mast€cells€and€Ô_ÔbasophilsÔ_ÔÐ X#!' Ðand,€when€antigen€is€bound€it€causes€the€basophil€(or€mast€cell)€to€release€histamines€andÐ 0$Ø!( Ðheparin€from€these€cells,€resulting€in€allergic€symptoms.Ð%°")P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àClinical€effects€of€Ô_ÔIgEÔ_Ô€mediated€reactions€include€increased€vascular€permeability,€skinÐ ¸&`$+ Ðrashes,€respiratory€tract€constriction€(wheezing),€and€increased€secretions€from€epitheliumÐ '8%, Ð(watery€eyes,€runny€nose).Ðh(&-P T$P T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àNot€much€else€is€known€about€its€biologic€role.Ð*À'/P T$P T$ ÐÌà   àà ø àf.à0 P àòòò òÔ_ÔIgEÔ_Ô€does€not€fix€complement€and€does€not€cross€the€placenta.ó óóóÐÈ+p)1P T$P T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àNo€blood€group€antibodies€have€been€reported€to€belong€to€this€class.Ðz-"+3P T$P T$ ÐÐ R.ú+4 Ðà0   à7.à0ø T$ T$àò òÔ_ÔIgDÔ_Ô€Classó óÐXøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àAccounts€for€less€than€1%€of€the€total€immunoglobulin€pool.Ð ´P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àThis€is€primarily€a€cell€membrane€immunoglobulin€found€on€the€surface€of€B€lymphocytes.мdP T$P T$ ÐÌà0   àà0ø T$ T$àc.€à0P øT$øT$àòòò òÔ_ÔIgDÔ_Ô€does€not€fix€complement€and€does€not€cross€the€placenta.ó óóóÐlP T$P T$ ÐÌà   àà ø àd.à0 P àLittle€is€known€about€the€function€of€this€class€of€antibody.Ð ÆP T$P T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àNo€blood€group€antibodies€have€been€reported€to€belong€to€this€class.ÐÎ v P T$P T$ ÐÌH.à0   àClinical€Significance€of€Blood€Group€AntibodiesÐ~ &  T$ T$ ÐÌà0   à1.à0ø T$ T$àòòClinical€significance€óóof€blood€group€antibodies€is€evaluated€by€their€ability€to€ò òòòproduce€hemolyticÐ .Ö  Ðtransfusion€reactionsó ó€or€ò òhemolytic€disease€of€the€newborn€(Ô_ÔHDNÔ_Ô)óóó ó.а øT$øT$ ÐÌà0   à2.à0ø T$ T$àTransfusion€reaction€is€the€term€used€to€describe€an€unfavorable€response€by€a€recipient€to€theÐ ºb Ðinfusion€of€blood€or€blood€products€andòò€include€the€followingóó:Ð’:øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àIn„vivo€hemolysis,ÐBêP T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àDecreased€survival€of€transfused€cells,ÐÂP T$P T$ Ðà0   àà0ø T$ T$àc.à0P øT$øT$àanaphylaxis,ÐòšP T$P T$ Ðà0   àà0ø T$ T$àd.à0P øT$øT$àgraft„versus„host€disease,ÐÊrP T$P T$ Ðà0   àà0ø T$ T$àe.à0P øT$øT$àpost„transfusion€Ô_ÔpurpuraÔ_Ô,ТJP T$P T$ Ðà0   àà0ø T$ T$àf.à0P øT$øT$àÔ_ÔalloimmunizationÔ_Ô,Ðz"P T$P T$ Ðà0   àà0ø T$ T$àg.à0P øT$øT$àsepsis€due€to€bacterial€contaminated€components,ÐRúP T$P T$ Ðà0   àà0ø T$ T$àh.à0P øT$øT$àand€disease€transmission.Ð*ÒP T$P T$ ÐÌà0   à3.à0ø T$ T$àHuman€red€blood€cells€contain€hundreds€of€blood€group€antigens€which€may€be€an€integral€part€ofÐ Ú‚ Ðthe€RBC€or€adsorbed€onto€the€RBC€from€the€plasma.вZøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àAt€least€15€different€blood€group€systems€have€been€recognized€in€humans.Ðb  P T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àIndividuals€may€produce€antibodies€to€these€blood€group€antigens€due€to€exposure€to€Ô_ÔRBCsÔ_ÔÐ º" Ðthrough€previous€transfusion€or€pregnancy.Ðê’#P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àTransfusion€of€Ô_ÔRBCsÔ_Ô€possessing€antigens€to€which€the€individual€has€antibodies€may€resultÐ š!B% Ðin€immune€hemolysis€of€the€transfused€cells.Ðr" &P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àThe€severity€of€the€reaction€depends€on€a€number€of€factors,€including€the€characteristics€ofÐ "$Ê!( Ðthe€antibody€class€involved.Ðú$¢")P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àAntibodies€to€the€ABO€system€antigens€are€òòusually€IgMóó,€cause€complementÐ ª&R$+ Ðactivation€andòò€ò òintra€vascular€hemolysisóóó ó.Ђ'*%,¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àOther€RBC€antigens€induce€formation€of€òòIgG€class€óóantibodies€which€may€causeÐ 4)Ü&. Ðaccelerated€RBC€destruction€ò òòòextra€vascularlyóó.ó óÐ *´'/¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àSymptoms€may€include€fever,€low€back€pain,€nausea€and€vomiting,€circulatoryÐ À+h)1 Ðshock,€anemia,€jaundice,€and€kidney€failure€which€may€ultimately€result€in€death.И,@*2¨ T$¨ T$ ÐÌÌÐ  /È,5 Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àSecondary€response€symptomatic,€primary€response€may€be€asymptomatic€due€toÐ X Ðslow€destruction€of€Ô_ÔRBCsÔ_Ô.Ð0ب T$¨ T$ ÐÌà0   à4.à0ø T$ T$àTransfusion€reaction€to€other€components€of€blood,€WBC€and€platelets,€are€very€common,€butÐ àˆ Ðreactions€are€not€as€severe€as€RBC€reactions.и`øT$øT$ Ðà0   àà0ø T$ T$àà0P øT$øT$àÐ P T$P T$ Ðà0   à5.à0ø T$ T$àAn€additional€adverse€effect€is€disease€transmission,€which€can€only€be€prevented€by€careful€donorÐ h Ðscreening.Ð@èøT$øT$ ÐÌà0   à6.à0ø T$ T$àSome€adverse€effects€can€be€prevented,€some€cannot.€€The€primary€duty€of€Ô_ÔImmunohematologistsÔ_Ô€isÐ ð ˜  Ðto€provide€serologically€compatible€blood€and€blood€components€for€transfusion.ÐÈ p øT$øT$ ÐÌI.à0   àComplementÐx  T$ T$ ÐÌà0   à1.à0ø T$ T$àIntroductionÐ(Ð øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àThe€complement€system€is€an€integral€part€of€the€body's€immune€system€composed€of€moreР؀  Ðthan€25€Ô_ÔglycoproteinsÔ_Ô€which€circulate€in€the€plasma€in€an€inactive€form.аXP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àThese€proteins€can€be€activated€by€two€independent€pathway,€classic€and€alternative€orÐ ` Ðproperdin€pathways.Ð8àP T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àThree€primary€functions:ÐèP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àòòLysis€óóof€antibody€coated€cells,€such€as€bacteria€and€Ô_ÔRBCsÔ_Ô.И@¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àMediation€of€òòÔ_ÔopsonizationÔ_Ôóó,€preparation€of€foreign€cells€for€phagocytosis.Ðp¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àGeneration€of€peptide€fragments€that€òòregulate€features€of€the€inflammatory€andÐ Hð Ðimmune€responseóó.РȨ T$¨ T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àActivation€of€complement€results€in€a€cascade€or€interaction€of€the€complement€proteins,Ð Ðx Ðleading€to€generation€of€products€that€have€important€biologic€activities€which€includes:ШPP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àÔ_ÔopsonizationÔ_Ô,ÐX ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àimmune€adherence,Ð0Ø!¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àand€Ô_ÔchemotacticÔ_Ô€and€Ô_ÔanaphylatoxicÔ_Ô€activity.а"¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àIn€blood€banking€complement€is€important€in€two€major€areas:и `$P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àSome€antigen„antibody€complexes€cause€sufficient€quantities€of€complement€to€beÐ h" & Ðbound€to€Ô_ÔRBCsÔ_Ô€to€complete€activation€cycle,€causing€hemolysis.Ð@#è '¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àAntigen„antibody€complexes€initiate€complement€binding€in€such€a€way€that€allowsÐ ð$˜") Ðdemonstration€of€the€existence€of€such€complexes€by€the€use€of€serologic€techniques.ÐÈ%p#*¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àFresh€serum€is€necessary€to€ensure€adequate€quantities€of€viable€complement€as€complementÐ x' %, Ðis€unstable€and€heat€labile.ÐP(ø%-P T$P T$ ÐÌÌà0   à2.à0ø T$ T$àThe€Classic€PathwayÐØ*€(0øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àEleven€components€involved,€numbered€C1€to€C9.Ј,0*2P T$P T$ Ðà0   àà0ø T$ T$àb.à0P øT$øT$àComplement€cascade€requires€presence€of€cations,€both€calcium€and€magnesium.Ð`-+3P T$P T$ ÐÌÐ /¸,5 Ðà0   àà0ø T$ T$àc.à0P øT$øT$àActivation€of€the€classic€pathway€almost€always€initiated€by€immunoglobulin.ÐXP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àòòRequires€only€1€molecule€of€ò òIgMóó.ó óа¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àòòRequires€2€molecules€of€ò òIgGó óóó.Ð䌨 T$¨ T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àProcess€involves€cleavage€of€the€components€such€that€removal€of€part€of€the€complementÐ –> Ðmolecule€leaves€the€residual€portion€enzymatically€or€biologically€active.ÐnP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àCleavage€of€most€components€generates€small€fragment,€which€enters€plasma,€andÐ  Æ Ðlarger€fragment€which€attaches€to€surface€and€continues€in€the€reaction.Ðö ž ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àMajor€controls€are€inhibitory€proteins€(C1€and€C3€inhibitors),€spontaneous€decay,Ð Î v  Ðand€rapid€clearance€of€active€fragments.Ц N ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àActivation€is€divided€into€three€phases:€€recognition,€activation€and€attack.Ð~ & ¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àe.à0P øT$øT$àò òRecognition€Phaseó óÐ.Ö P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àC1€has€three€Ô_ÔsubcomponentsÔ_Ô,€C1q,€C1r,€and€C1s.Ð⊠¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àC1q€binds€directly€to€Immunoglobulin€molecule,€C1r€and€C1s€and€requires€calcium.кb¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àC1r€and€C1s€become€enzymatically€active.Ð’:¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àC1r€cleaves€C1s,€C1s€cleaves€C4€and€C2€to€initiate€the€activations€phase.Ðj¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à5)à0¨ P T$P T$àRecognition€unit:€ò òC1q,C1r,C1s.ó óÐBê¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àf.à0P øT$øT$àò òActivation€Phaseó óÐöžP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àActivated€C1s€cleaves€C4€and€C2,€which€begins€the€activation€phase.ЪR¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àC4€cleaved:€€C4a€released€to€plasma€and€decays€rapidly,€C4b€binds€to€target€cellÐ ‚* Ðsurface.ÐZ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àC2€cleaved:€€C2a€released€to€plasma,€C2b€remains€bound€to€C4b.€Requires€calciumÐ 2Ú Ðand€magnesium.Ð ²¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àC4bC2b€cleaves€C3€to€C3€Ô_ÔconvertaseÔ_Ô€which€cleaves€C3€into€C3a€and€C3b,€whichР⊠Ðattaches€to€the€target€cell€surface€near€the€C4b,2b€complex.кb¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à5)à0¨ P T$P T$àC3b€actually€a€complex€of€C3c€and€C3d.Ð’:¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à6)à0¨ P T$P T$àSometimes€C3b€binds€to€surface€whereas€other€times€C3d€binds,€binding€of€C3bÐ j  Ðinitiates€phagocytosisÐBê!¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à7)à0¨ P T$P T$àC4b,2b,3b€complex€(C5€Ô_ÔconvertaseÔ_Ô)€splits€C5€into€C5a€which€is€released€into€plasmaÐ Â" Ðand€C5b€which€attaches€to€cell€membrane€and€is€the€nucleus€for€formation€ofÐ òš# Ðmembrane€attack€complex.ÐÊ r$¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à8)à0¨ P T$P T$àActivation€Unit:€€ò òC4b,C2b,C3b,C5bó óТ!J%¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àg.à0P øT$øT$àò òAttack€Phaseó óÐV#þ 'P T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àOnce€membrane€bound,€C5b€binds€C6€and€C7€by€adsorption.Ð %²")¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àThis€complex€attaches€to€the€cell€membrane€and€binds€C8€and€a€variable€number€ofÐ â%Š#* ÐC9€molecules.к&b$+¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àComponents€ò òC5b,C6,C7,C8€and€C9ó ó€comprise€the€terminal€membrane€attack€unit.Ð’':%,¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àBecomes€embedded€in€the€cell€membrane€and€forms€a€central€pore€or€hole,€whichÐ n(&- Ðresults€in€a€change€in€membrane€permeability.ÐF)î&.¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à5)à0¨ P T$P T$àMembrane€then€loses€its€ability€to€retain€cellular€contents€and€prevent€entrance€ofÐ *Æ'/ Ðextracellular€material€such€as€water.Ðö*ž(0¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à6)à0¨ P T$P T$àLoss€of€cellular€integrity€results€in€rapid€cell€death€and€lysis.ÐÎ+v)1¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à7)à0¨ P T$P T$àClassic€pathway:€€ò òC1,C4,C2,C3,C5,C6,C7,C8,C9ó óЦ,N*2¨ T$¨ T$ ÐÌÐ Z.,4 Ðà0   à3.à0ø T$ T$àAlternative€(Properdin)€PathwayÐXøT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àProteins€in€the€alternative€pathway€perform€activities€similar€to€those€in€the€classic€pathwayÐ ° Ðbut€are€usually€ò òòònon„antibodyóóó ó€triggered.ÐàˆP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àAny€one€of€a€variety€of€substances€can€initiate€complement€activation€including:Ð’:P T$P T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àbacterial€Ô_ÔpolysaccharidesÔ_Ô€and€Ô_ÔlipopolysaccharidesÔ_Ô,Ðj¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àÔ_ÔendotoxinsÔ_Ô,ÐBê¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à3)à0¨ P T$P T$àcobra€venom,Р¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à4)à0¨ P T$P T$àÔ_ÔtrypsinÔ_Ô€like€enzymes,Ðò š ¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à5)à0¨ P T$P T$àand€aggregates€of€Ô_ÔIgAÔ_Ô€and€IgG4€that€do€not€activate€C1.ÐÊ r ¨ T$¨ T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àC1,€C4€and€C2€do€not€participate.Ðz " P T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àAlternative€pathway:€€ò òC3,C5,C6,C7,C8,C9ó óà0`P T$P T$àÐ*Ò `T$`T$ ÐÌà0   à4.à0ø T$ T$àRegulation€of€the€complement€cascade.ÐÞ† øT$øT$ ÐÌà0   àà0ø T$ T$àa.à0P øT$øT$àActivation€of€complement€cascade€results€in€complex€series€of€molecular€event€with€potentÐ Ž6 Ðbiologic€consequences.ÐfP T$P T$ ÐÌà0   àà0ø T$ T$àb.à0P øT$øT$àModulating€mechanisms€are€necessary€to€regulate€complement€activation€and€controlÐ ¾ Ðproduction€of€biologically€active€split€products.Ðî–P T$P T$ ÐÌà0   àà0ø T$ T$àc.à0P øT$øT$àFirst€mechanism€is€spontaneous€decay€of€activated€components.ОFP T$P T$ ÐÌà0   àà0ø T$ T$àd.à0P øT$øT$àSecond€mechanism€€involves€specific€control€proteins€that€modulate€the€activity€of€certainÐ Nö Ðcomplement€components€at€critical€activation€steps.Ð&ÎP T$P T$ ÐÌà0   àà0ø T$ T$àà0P øT$øT$à1)à0¨ P T$P T$àC1€inhibitor€blocks€activities€of€C1r€and€C1s.ÐÖ~¨ T$¨ T$ Ðà0   àà0ø T$ T$àà0P øT$øT$à2)à0¨ P T$P T$àOther€factors€inhibit€activation€of€other€complement€components.ЮV¨ T$¨ T$ ÐÌÔ% € Ôà0   àà0ø T$ T$àe.à0P øT$øT$àA€number€of€proteins€act€to€control€the€membrane€attack€unit.Ð^ P T$P T$ ÐÌÌÌÌÌÌÌÌÌà   àà ø àà P àà ¨ àà  àà X àà ° àà  àà ` àà ¸ àà  à