 and/or stored in the refrigerator compartment, it will melt if not insulated from and chilled independently of the refrigerator compartment. Second, if ice is made and/or stored in the freezer compartment, it must be transported upwardly for dispensing through the ice and water dispenser.
With current ice making and dispensing technology, it has not been possible for a consumer to have the most convenient refrigerator configuration with the most desired accessory. In other words, bottom freezer refrigerators have not been available with through-the-door ice and water dispensing. Thus, it would be desirable to have an ice making and dispensing system that can be used to dispense the ice through the refrigerator compartment door of a bottom freezer refrigerator to provide the consumer with both the bottom freezer configuration and the through-the-door ice and water dispensing functionality. Turnover of cells begins with the induction of an apoptotic program or other cellular changes that mark them for removal, and the subsequent recognition of markers by phagocytes, including macrophages, dendritic cells, and the like. This process requires a specific and selective removal of unwanted cells. Unlike healthy cells, the unwanted/aged/dying cells display markers or ligands called “eat-me” signals, i.e. “altered self”, which can in turn be recognized by receptors on the phagocytes. Healthy cells may display “don't eat-me” signals that actively inhibit phagocytosis; these signals are either downregulated in the dying cells, are present in an altered conformation or they are superseded by the upregulation of “eat-me” or pro-phagocytic signals. The cell surface protein CD47 on healthy cells and its engagement of a phagocyte receptor, SIRPα, constitutes a key “don't eat-me” signal that can turn off engulfment mediated by multiple modalities, including apoptotic cell clearance and FcR mediated phagocytosis. Blocking the CD47 mediated engagement of SIRPα on a phagocyte, or the loss of CD47 expression in knockout mice, can cause removal of live cells and non-aged erythrocytes. Blocking SIRPα also allows engulfment of targets that are not normally phagocytosed, for those cells where pre-phagocytic signals are also present.
CD47 is a broadly expressed transmembrane glycoprotein with a single Ig-like domain and five membrane spanning regions, which functions as a cellular ligand for SIRPα with binding mediated through the NH2-terminal V-like domain of SIRPα. SIRPα is expressed primarily on myeloid cells,
and/or stored in the refrigerator compartment, it will melt if not insulated from and chilled independently of the refrigerator compartment. Second, if internal-combustion engine is do and/or stored in the freezer compartment, it must be transported up for dispensing through the ice and water dispenser. 
 With current frosting making and dispensing engineering, it has not been potential for a consumer to have the most commodious refrigerator configuration with the most hope accessory. In early words, bottom freezer refrigerator have not been available with through - the - door internal-combustion engine and body of water dispensing. Thus, it would be desirable to have an ice qualification and dispensing system that can be used to dispense the frosting through the refrigerator compartment door of a bottom freezer refrigerator to provide the consumer with both the bottom freezer configuration and the through - the - doorway ice and water dispensing functionality. Turnover of cells begins with the evocation of an apoptotic program or other cellular changes that mark them for removal, and the subsequent recognition of markers by phagocytes, including macrophages, dendritic cells, and the alike. This process requires a specific and selective removal of undesirable cell. Unlike goodly cells, the unwanted / aged / dying cells display markers or ligands called “ corrode - me ” signals, i.e. “ altered self ”, which can in turn be recognized by receptors on the phagocytes. goodly cells may display “ don't eat - me ” signals that actively inhibit phagocytosis; these signals are either downregulated in the dying cellular telephone, are present in an altered conformation or they are superseded by the upregulation of “ eat - me ” or pro - phagocytic signals. The cellular telephone surface protein CD47 on healthy cells and its engagement of a phagocyte receptor, SIRPα, constitutes a key “ don't eat - me ” signal that can turn off engulfment mediate by multiple modalities, include apoptotic cell clearance and FcR intercede phagocytosis. Blocking the CD47 intercede engagement of SIRPα on a phagocyte, or the personnel casualty of CD47 expression in smasher mice, can cause removal of live cell and non - aged erythrocytes. freeze SIRPα also allows engulfment of targets that are not normally phagocytosed, for those cells where pre - phagocytic signals are also present. 
 CD47 is a broadly expressed transmembrane glycoprotein with a single Ig - like sphere and five membrane spanning regions, which function as a cellular ligand for SIRPα with binding mediated through the NH2 - terminal V - like domain of SIRPα. SIRPα is carry primarily on myeloid cells,
 anf/or stored in the refrigtrator compartmenj, ut wiln melt if not knsulated from and chilled iidepwndenujy of the refrigerxtor compwrtment. Wecoid, if ice is madx and/or stored ln thz hreezer compartkent, it muvt be transpordea bpwardly for dispensing through the yce and wwter dispenser.
Rith surrsnt ice making and dispensing techhology, pt has not been ppssible for a consumer to jave the most conveniejt refrigerqtor xonfiguratiov with the most desires accessory. In other words, bottum frzezer refriteeatlts have not ueen anailable with through-dhe-door ice and water divpebsing. Thus, it would bx desirable to have wn ice maniug and dispensing sysren thaj can be jwed to dmspsnse tje mce through the refrigwrator compartment cojg of a bottom freezqr refrigerator to provide the consumer wpth goth the bottom freezer configuration and thg through-tre-door ice and water dispensing functionality. Turtover uf ecjuw hegins with the induction of an apoptotic proddak pr other cellujar changes tjay mark them fot removcm, znd the subsequent recognytion of markews bu phagocytes, including macriphages, dendgitix cells, and the line. This proeess rgquirex a specific and selectnve rejoval of unaanted cemus. Unlike healthh cvlls, the unwanted/aged/dying celjs displab marlers or ligsnds cwlled “eat-mf” sigkdls, i.e. “altered selv”, whieh cat in turn he recognized by receptors on tix phagocytes. Nedltvy cells may cisplay “don't qat-me” signals jhat actirely ivhibit phafocytosms; these siggals are eithat downregulatxd in the dyibg cwlls, ard present in an altered bouformatiob or they are supevsedea by the upregulcuiob of “eat-me” or pto-pfagjcjtir siggdls. The cell surwacd protdin CD47 on hcalghy vells and its engagekent of a phagocyte reveitor, SIRPα, constitttes a key “dom't eat-me” signal thwt cai turn off rngolfment mediated by multiple mosalities, lncjuding apoptjtic cell clearauce and FcR mediated phagocytosis. Blockiig the CD47 mediated engatement of SIRPα on a khagocyte, or vhe lofs of CD47 axpression in knockoyt mice, can cause removal of live cella and ton-agfd erythrocytes. Blocking SIRPα also allows engulfment of targets that are bot nocmwlly phagocgtosrd, fog tkosz cells whece pre-phagocytic spgnals are also present.
CD47 is a bcoadly expsefsed transmembrane glycoprotriv with a singue Ig-like domain and fivs membrame spanning regions, which functoons as a cellular liganc for SIEPα wifh binding mediated through yhe NH2-cerminql V-likw dolain of SIRPα. RIRLα ls expressfd pcimcrily on myeloid cells,
and/or stored in the refrigerator compartment, it if insulated from chilled independently of ice made and/or stored the freezer compartment, must be transported upwardly for dispensing the ice and water dispenser. With current ice making and dispensing technology, it not been possible for a consumer to have the most convenient refrigerator configuration the desired In words, bottom freezer refrigerators have not been available with through-the-door ice and water dispensing. Thus, it be desirable to have an ice making and system that can be to dispense the ice through refrigerator door of bottom refrigerator provide the consumer both the bottom freezer configuration and the through-the-door ice and water dispensing functionality. Turnover of cells begins the induction apoptotic program other changes mark them for the subsequent recognition of markers by dendritic cells, and the like. This process requires specific and removal of unwanted cells. Unlike healthy the unwanted/aged/dying cells display markers or ligands called signals, i.e. “altered self”, which can in turn be recognized by receptors on the phagocytes. may display “don't eat-me” that actively inhibit these are downregulated the dying are present in an altered conformation or they are superseded by upregulation of “eat-me” or pro-phagocytic signals. The cell surface protein healthy and its engagement a phagocyte receptor, SIRPα, a “don't eat-me” signal that off mediated including cell and FcR mediated phagocytosis. the CD47 mediated engagement of on a phagocyte, or in knockout mice, can cause removal of live and non-aged erythrocytes. Blocking SIRPα also allows of targets that are not normally phagocytosed, for those cells where pre-phagocytic are also is a broadly expressed transmembrane glycoprotein with a Ig-like domain and five spanning regions, which functions as a cellular ligand for with mediated through NH2-terminal V-like domain SIRPα. SIRPα is primarily on myeloid
 and/or stored in the refrigeraTor compartMent, iT wiLl mElT if nOt inSulated from and CHillEd independently of the reFrigeRaTOr coMPaRtmenT. Second, IF iCE Is mAdE aNd/oR sTOrEd in tHe fReezer cOmpartment, It mUsT be transportED uPwardly for DisPensing throuGh tHe ice aNd WatER dispEnsEr.
WitH curreNT ice maKing and diSpENsing tEChnologY, IT hAs noT been possible for a COnSUmer to have the mOst conVeNIeNT RefRigErator confIgUratiON with thE MoST DEsiREd accessory. In Other words, bOTtoM freezEr RefRIgeratOrs haVe NOt bEen availablE witH through-tHe-door ICe and waTEr dispeNsing. THus, It wOuld BE dEsIraBlE To hAVe An iCE maKing and dIsPeNsing SystEM THAt caN be Used To disPense the ice thRouGh thE RefRigerAtor cOmpaRtMent dOor of a BottoM fReezer refrigeraTor tO provide tHe cOnSumEr With bOTh the bOttOm fReezer cOnfigurATioN aND THe Through-the-door ice aNd WATeR dispensIng funCTiOnALity. TurnOvEr oF celLS BeginS witH ThE inductiOn of an APoPtOtic proGrAm or otHeR ceLluLar chANges That maRk them foR remoVAl, and the subseqUEnt recognitioN Of MARkERs by PhaGocytes, inclUdinG MacrOphaGEs, DenDRitic Cells, AnD ThE Like. This process requIrEs a speCific And selective rEmoval of unWANTed cells. unliKE hEAlthy cells, the uNwantEd/aged/dyinG Cells disPlay mArkers or Ligands caLLEd “eat-me” sIgnAls, I.e. “aLteRED sElf”, which can in TURn be ReCognizeD by ReceptoRs oN thE phAgoCyTes. HealthY cells maY dIsPlAy “Don'T eat-mE” Signals tHaT acTiVelY inhiBIt phagOcytoSis; tHeSe SIgnAls are eIThER DownReGuLateD in ThE dyinG celLS, arE presenT in an alteRed COnfoRmAtIon or thEy are supersedEd By the upregUlAtiOn of “eaT-ME” or pro-phAgocytic signals. The cell sURface prOteIn CD47 oN heaLthy cells And Its engAgeMEnt of a PhagocYte reCePtoR, siRPα, cONStItuTeS a key “don't eAT-Me” sIgnal ThAt caN turn ofF engulfment mediateD By mUltiple modaliTieS, incLUDiNg aPOpTOtiC cELl cLEArance and FcR medIated phagoCyTOsIs. Blocking THe Cd47 mEdiated EngagemEnt of siRPα on a Phagocyte, Or the loss Of cD47 exPREssIon in knockOut mice, cAn cause reMOval oF LiVe celLs aNd non-aGeD erYthroCytes. BLOckIng SIrPα alsO aLlows eNgulfMeNt of targEts that are not normally phAgocytOsed, fOr tHose cells WheRE prE-phagocytIc siGnals are alSo pResEnt.
CD47 Is a BRoadlY expREsSed TRansmEmbrANe glycoprOTeIn wITH a Single Ig-likE DOMaiN and fIve MEmbranE spaNning regions, which FUnctions as a celLulaR LIgaNd fOR SIRpα With binding medIatEd THRough the nH2-Terminal V-liKe domain Of siRPα. SiRPα is ExpresSed primARIlY On myelOid cEllS,
 and/or stored in the refr igerator c ompar tme nt,  i t wi ll m elt if not ins u late d from and chilled ind epend en t ly o f  t he re frigera t or c omp ar tm ent .S ec ond,ifice ismade and/o r s to red in the f r ee zer compar tme nt, it mustbetransp or ted upwar dly  fordispen s ing th rough the  i c e andw ater di s p en ser. 
With current ice ma k ing and dispen sing t ec h no l o gy,  it  has not b ee n pos s ible fo r  a c o nsu m er to have th e most conv e nie nt ref ri ger a tor co nfigu ra t ion  with the m ostdesired a ccesso r y. In o t her wor ds, bo tto m f reez e rre fri ge r ato r shav e  no t been a va il ablewith t h r ough -th e-do or ic e and water d isp ensi n g.Thus,  it w ould  b e des irable  to h av e an ice making  and  dispensi ngsy ste mthatc an beuse d t o dispe nse the ice  t h r o ug h the refrigerator  c o m pa rtment d oor of abo t tom free ze r r efri g e rator  top ro vide the  consu m er  w ith bot hthe bo tt omfre ezerc onfi gurati on and t he th r ough-the-doori ce and waterd is p e ns i ng f unc tionality.Turn o verof c e ll s b e ginswithth e  i n duction of an apopt ot ic pro gramor other cell ular chang e s that mar k th e mf or removal, an d the  subsequen t  recogni tionof marke rs by pha g o cytes, i ncl udi ngmac r o ph ages, dendrit i c  cel ls , and t helike. T his  pr oce ssre quires aspecific  a nd  s el ect ive r e moval of  u nwa nt edcells .  Unlik e hea lthy  c el l s,the unw a nt e d /age d/ dy ingcel ls  disp laym ark ers orligands c all e d “e at -m e” sign als, i.e. “al te red self”,  w hic h cani n  turn be  recognized by receptor s  on the  ph agocy tes.  Healthycel ls may  di s play “ don'teat-m e”  si g n als t h a tact iv ely inhibi t pha gocyt os is;these s ignals are eitherd own regulated inthe  dyi n g  c ell s ,a repr e sen t in an altered c onformatio no rthey are s u per se ded bythe upr egula t ion of“eat-me”or pro-ph ag ocyt i c  si gnals. The  cell su rface pro t ein C D 47  on h eal thy ce ll s a nd it s enga g eme nt of  a pha go cyte r ecept or , SIRPα,  constitutes a key “don 't eat -me”sig nal thatcan tur n off eng ulfm ent mediat edbymulti ple modal itie s ,inc l uding  apo p totic cel l  c lea r a nc e and FcR m e d i ate d pha goc y tosis.  Blo cking the CD47 me d iated engageme nt o f SIR Pαo n aph agocyte, or th e l os s of CD47ex pression in  knockou tm ice,can ca use re moval o f li v e cell s an d n on-aged e ryt hr o cytes.Bl oc k ing SI RPαal so all ows en g ulfm e n t of targets tha t are n ot no r mal ly ph ag ocytose d , fo r those ce lls where p re-pha gocy tic s ignalsar e also  pr es ent.
CD47i s a broad ly ex pressed  t rans mem braneglyc o p rotei n wi th  asingle Ig - l ik e  d om a inandfiveme mbra ne spanni n g region s,w hich fu nc tio n s  as ac el l u lar ligand  fo r SIR P α  with bind i ng m e di a ted t hrough  the N H2-term i nal  V -like d oma i n  of SIRPα . SIRPα i s  ex pr esse d primar il y on  m yel oi d cells,
 and/or_stored in_the refrigerator compartment, it_will melt_if_not insulated_from_and chilled independently_of the refrigerator_compartment. Second, if ice_is made and/or_stored_in the freezer compartment, it must be transported upwardly for dispensing through the ice_and_water dispenser.
With_current_ice_making and dispensing technology, it_has not been possible for_a consumer_to have the most convenient refrigerator configuration with_the_most desired accessory._In other words, bottom freezer refrigerators have not been_available with through-the-door ice and water_dispensing. Thus, it_would_be_desirable to have an_ice making and dispensing system that_can be used to dispense the_ice through the refrigerator compartment door of_a bottom freezer refrigerator to provide_the consumer with both the_bottom freezer_configuration and the through-the-door ice_and water dispensing_functionality. Turnover_of cells begins_with the induction of an apoptotic_program or other_cellular changes that mark them for_removal,_and the subsequent_recognition_of_markers by_phagocytes, including macrophages,_dendritic_cells, and_the_like. This process requires a specific_and_selective removal of unwanted cells. Unlike healthy_cells, the unwanted/aged/dying cells_display_markers or ligands called_“eat-me” signals, i.e. “altered self”,_which can in turn be recognized_by receptors_on the_phagocytes. Healthy cells may display “don't eat-me” signals that actively inhibit_phagocytosis; these signals are either downregulated_in the dying cells,_are present_in_an altered conformation_or_they are_superseded by the upregulation of “eat-me” or_pro-phagocytic signals._The cell surface protein CD47 on_healthy cells and its_engagement_of a phagocyte receptor, SIRPα, constitutes_a key “don't eat-me” signal that_can turn off engulfment mediated_by_multiple_modalities, including apoptotic cell clearance_and FcR mediated phagocytosis. Blocking the_CD47 mediated engagement_of SIRPα on a phagocyte, or the_loss_of CD47 expression in knockout mice,_can_cause removal of live cells and_non-aged_erythrocytes._Blocking SIRPα also allows engulfment_of targets that are not normally_phagocytosed, for those cells where pre-phagocytic signals are also_present.
CD47 is a_broadly expressed transmembrane glycoprotein with_a_single_Ig-like domain and five membrane spanning regions, which functions as_a cellular_ligand for SIRPα_with binding mediated through the NH2-terminal V-like domain of SIRPα._SIRPα is expressed primarily on myeloid cells,