(SANITIZED)UNCLASSIFIED FOREIGN-LANGUAGE BROCHURE ON INSTITUTE OF BIOLOGY(SANITIZED)

• Document Type: CREST
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80T00246A002900500018-6
• Release Decision: RIFPUB
• Original Classification: K
• Document Page Count: 72
• Document Creation Date: December 21, 2016
• Sequence Number: 18
• Content Type: REPORT

Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
L`ESKOSLOVENSKA AKADEMIE V$D
ACADEMIA SCIENTIARUM BOHEMOSLOVENICA
FOLIA
BIOLOGICA
TOMUS II
FASCICULUS 5
-N11111?D~lllf lYl
I ~s~~~
~~~
Fol. biol. (Praha) Tom. 2 - Fasc. 5 Praha 31. 11. 1956
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
FOLIA BIOLOGIC'A (PRA[[A)
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mikrobiologie
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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OpraHli3Ma. ~OHj(ya nOKa3bIBaeT, K8K BO3HnKaIOT HBJICHHn BOCnaJICHHFI; OH O~Ha-
pyx{HJI o6paaoxaxne Me3eHXIIM8TO3HOI3 KanCyJIbI, II3OJIHpyIOH[eI3 HHOpOJjHOe TeJIO
OT TKaHeH 3apOj[bIIIIa. c~TO HBJICHI3e, B KOTOpOM yuac'rByloT KOMIIJICKCbI I{JICTOH,
HMeIOHjee OCHOBV B (~)arOulITapHbIX CBOHCTBaX KJICTOI{, HCCOMHCHHO MOSI{eT 6bITb
Ha3BaH0 BOCHaJIHTe7IbHOI3 peaKuHeli. c~TO - IIpOO~pa3 rOyJjyxjHX npoueccos Bocna-
JICHYIH, BCC 6OJIee yCTIOSKHHIOnjIIXCH IIO XOJ[y 3Mhp1iOHaJIbHOI'O pa3BHTHIi IIO Mepe
TOTO, KaK npOHCXOJjHT JIH(~(~epeHuHaijHH KJICTOK, TKBHeH n pa3BHTYIe OpraHOB.
Ha 6-S-bie cyTKn o6Hapyx{HBae'rcx n cocy~zHCTaH peal{uHH c BbiceJlexueM JIefIKO-
IjHTOB. J11O6OnbITHO, LITO (~OpMnpyIOII[aHCn Me3eHXHMaTO3Hafi KaHCyJIa IIOCTeneHH0
RerexepllpyeT 13 o6paayeTCti BTOpHUxaII - ~ix6po6JIacTHUecxax xancyaa. IIo Mepe
uaJlbxeiiHleH Anc~c~epexunauHH xJle'ro~Ixbix aJieMeHTOB n HouBJIexI3H sce 6onee cneuna-
JiHaHposaxxbix c~opM, Hpno6peTaeT Bce HOBOe H Hosoe couepx{axl3e HsJlexlie Bocna-
JiexHIl.
RoH~jya RoxaaaJl, ~ITO soaxnxaeT xa 6aae .
B HaCTOfliuee BpeMH IIl)OBO~jBTCII aHaJIOTHiIHble HCCJIeZ[OBBHnH Ha MJICKOHIITaIOIIjnX
n IIpO~JICMa HaLIIIHaCT pa3pa6aTbIBaTbCH B HJIBHe CpaBHHTeJIbHOi3 aM6pHOJIOrnH.
B 3TOM MbI BHjjHM Z[aJIbHeHIIIee pa3BHTne nOJ[XOJ[OB 1'I. ICI. N1CiIHYIKOBa K nay~IexHlo
nsnexHH BocnaJieHHH.
2. Ll.~..+ti~r~or~o~uuec~oe axa+Iexue o6o.~o~Ie~c s~uu arcnaomtcbax
B Hayuxo-Jla6opa'ropxoM o6nxoRe xax{eTCH caMO co6oai paayMelouinMCR aaninTHOe
3HaiICHHe O~OOJIOLICK HHu H{HBOTHbIX. OJjHaKO, C)OJIbHIRHCTBO HCCJICZ(OBBTeJICH CKJIOHHO
paCCMaTpHBaTb O~OJIOLII{H HHu JIHHIb HaK MCXaHHLICCKHe ~apbepbl, IIpeIIHTCTByIOIuAC
HpOHHKHOBCHIiIO ~aKTepnli, rplihOB, npOCTeIinIHX. B CBA3n C IIpO6JICMOIi YIMMyHK-
TCTa 3apOj[bIHIen B HaHICn Jla6opaTOpnH yj(eJIHeTCH hOJIbIIIOe BHI3MaHHC OhOJIOiI-
I{aM Hnu.
OCOCeHHO O~IHHpHble HCCJIej[OBaHHIi npOBOT,[HTCH 1{OpOTI{OBOIi (1952, 1953, 1956)
xa x~iuax HTHu? EIO, I'Hp(~iaxosoii (1949) H RpyrHMH o6xapy~xex pslu IlxTepecxbix
HsneHHi3.
1. IIO~jTBep?KZ[eHbI (H 3HatiIHTCTIbHO paCIIIHpeHbI) JjaHHble j[pyrHX aBTOpOB O 6aKTC-
pYiuHJjHbIx csoHCTBax 6eJrKOSOii o6oJ~ovKn H~ua xypnu~ n xHu uPyrHx nTnu.
2. j~oxaaaxbl axeprHUHbie npoTHCTOuHRxbie n c~yxrnuliRxbie csoilcTBa 6eJlxosoii
OOOJIO~IKH. 1leKOTOpbIC MHKpOOpraHH3MbI HpaKTH9eCI{n MOMCHTaJIbHO IIOri36aIOT Hpx
KOHTaKTe C (HaIIpnMep, Sarcina lutea).
3. AHTH6noTII~IecKHe csoHCTBa xaTypanbxoro 6eJIKa uaJlexo xe coBHaualoT co csoii-
CTBaMH IJIII3OuILMa>, pa3JIH~IHbIM CIIOCOC)OM HOJIyiIaeMOI'O H3 GeJIKa: pa3JII3iICH CIICKTp
aHTHMnI{pOCHOTO j[eHCTBHH, MOHjHOCTb aHTn6nOTHLIeCI{HX CBOIICTB, paaJln~IHa Jjnxa-
MHI{a H3MCHCHIiH aHTHMHKpOrOHb1X CBOIiCTB Ii B XOj[e HHKy-
6auHli H T. A.
I~OpOTKOBa H TOKHH CtIHTaIO'C, LITO Tpe6yeTCII paJjIIKaJIbHbIIi HepeCMOTp HOHHTHH
.
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
~I. ~3y~1CH0 H3MCHCHHC II ~)UTHCTOI~H;(HbIX, l~)~'HTIII~LI~[HbIS II (lali'PC~)H[~Hj[1{bIX
CiIOIICTB ~ETIICa B XOj(C 9MF~aOHflJlbIlO1'O ~a3RHTbIII. ~CTBHOIiIIM('.fl Hit ~Bf~TC[)HI~H;[HbCl'
CBOIICTiIRl. ~3y9CH0 ;l,Ca('TB14C F)CTf~Ca H8 }3a(i. SU~)~I~JS~ tail('. IllC~8tI1CPIUi11, t~81'.
meseutericus, 13. prodig?iosum, }3. Iluoresc,eus, ~~icrococcas 1~-sudeilaicus it Sarciua
lutea.
OleaaaTlocb, aH~~I16uu~rH~ecl:HC csoiicTSa Ho ao,~~~ paasIITIIII McnslxlTCU IuI paaHOMy
II aasacuMOCTU oT ol~~r>ertil~a. TaI., s oTHOmeuIIII Sarciua latex, 13ac. mesenteril?~us
II I3ac. subtilis arcTUSHOC~~I'> ~enrca coapaHHelcu uTaocH~re~hao aoc~roHxsoii s ~~eveHlao
Iiepsblx CeMH )tnei~ rlaaHllrwR ~Iapo~hlula, a arc~rllsHOCTS Fcan.a H o~~HOIHeuHa }~. pro-
digiosum, }3. iluoresc,eus I2 Bac. megatllerium nuc~reHeHHO cHwx;aeTCII II cxu~~N~~
HA HCT I# 6-7 ;(HII'.1l 11HIf "~c~I Ii II. ~TII a ~
3 [ ,tpvrHC ~axHVle }%oe,h~~alo~r l~upo~ricosy
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IfOM}'-.;II7OO O~HOM}" RCIIlCC9B~' LATIN aPBHTy, Nc~II})IIMO~, IC KT[a3O7~aM~'~>.
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aMIIHOTHiIOCHOlI >14H;[kOCTII H~'~I1HOPU 3a})O~[blIDa. ~ ]t(;jjaIIHCC H~)C:VIII TBIIIIC~)Hl)N
lT tIOICO~HOH ~1~~J.J~, 1~8TO3IIHOII H ~[~)yl'HMH yCTaIiOHTICiI Oi1OH}, IIH'1'C[)CCH6llI J~J[H
3M~~HOTIOPHH (~aICT: c ~2 ;~HH I1 }Ili~'~BII;VIH hOTIOK Hi19HHaC1' 1,IOCT~~IIaT6 IIO ('('~)O.;}IO-
aMHHOTH~IOCICOMV XO,i cpaslnrreTltiaoii anlFi~Iao.~oruH.
?3. ,]Fnr~~ro~IOrrulvec~rce c~oru~>r~~a s~,rnf .~z.~e~oiarl~nair,~~ru.r
'1'orcHH II Ilhi~ua~rusa (14)53 ri, s, r) ul~Ha~>y;i;a.-~II aIl~rHmuu.~x~oiu.ic cixliic~rl;a slHu
nlTielcunw~ralouui~ Ha seer cTa;~IIIIa passw~rnsl ;lo ua II:vIIi~IalrrarliIll s crreHr.~- Ma~rl.u.
(hlr~Il~aMU Ha 85 aapo,~hlma~ IcpoTruxa T~o~:a:Iauo, vTO ,rn,u:oc.Tl, nunoc'rII ~nac~rultllc~rl>i
IcpoT~Hica o6Tia,~ae~r shrl~ax~eHIIVIMH 6art~repHl~ul~uhiv~Il csoiicTSaNHa. (_:-rasllTalc~~ orn,rri~i
in viCro (IUHpuI~enl oTCachlsaTracb >hu;~ICOCTb IwTwc~~Il 6nacTOuilc~~Ll a Hc,cTic;u~saTau?i~
ee 6arc~~eplluHlplble csoi~cTSa) a in vivo: Ha %-8 i[eII>, nocTre coital, Hni~~Hr~enl esoT~H-
a~oc.v It uoaxx;~rh 6TIacTOr~acTht 0,05 :~~ 6ar;lepHa:n,HOii :~M}~.nl>cwu H ;te.~ia.~naci~ aa~renl
sr,rcesl>i Iia nuTa~~carr>HVIO cpeny.
'hurtlln II ~IhITIaTOSa (11J53a) y ielluTluer. s ~~oa~I, vl~u aNUUlu~ruvucl.as~ H aTlTiarrroa,~uaH
xiH;~rsoc~rH ~opcxux csIlllox i~ IcpoTlHybHx o~~.na;~alo1 Hcuo s~~ipi1}I:cullhliVlH ~iairreClia-
L~HJjH6iMH CBOHCTB8MI1.
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
4. ~op.~uoo6pasoearr~er~bxbae i~Ipor{eccai a u.rc.~z~uo.~oau~ec~ue pen~cr{uu
AJIft aM6pxoJiorHx oco6o Bax{xo HccneAosaHHe cooTHOmexHIl (~iopMOOO'paaosa-
Tenbxblx npoljeccoB II HMMyxoJlorH~IecKxx peaxuHii.
Yx{e MeuxHl{oB x oT~IacTx IfoBaJlescKHii npx~asaJlx 6oJIbBloe (~iopMOO6paaosa-
TeJIbHOe 3Ha9eHHe HMMyHOJIOTHLIeCKHM peaKIjIIHM. MbI H0 HMeeM BO3MOIKHOCTH
B 3TOII CTaTbe IIOJjpO6H0 x3JlaraTb MHOI'IIe xX pa6OTbI. Me~IHIIKOB fIOKa3aJI, HBIIpII-
Mep, iLTO (~)arOI[HTapxble peaKljxll HrpaloT 6OJIbIIIyIO pOJIb B llpOIjeCCax M0T8MOp(~)O3a
aM(~H6Hx. KOBaJIeBCKxH O6HapyHCI7JI 3Ha9OHHe (~arOljx'CapxblX peaL:Ij11TI B ftBTICFIHHX
MOTBMOp(~O3a MyX.
ECJIH calla JIOrHKa paasxTxft HccJreAosaxHK B xaxoH JIH6o o6JiacTH axaxNir npNBO-
jjxT K HOO6XOJjxMOCTx CO3JjaHHft HOBbIX rx1IOTe3, TO COOTBOTCTByIOH[He Li;[eI1, KdK rOBO-
pftT, HaLIIIHaIOT ((HOCHTbCH B BO3Z[yXe>). 1IOBHj[HMOMy, HOO6XO~lI\iOCTb CBft3x MeiKZ(y
iIMMyHOJIOPxeH H 3M6pxOJIOTHex Z[OCTaTOLIHO CO3peJIa, eCJIH B IIOCJIOIjHxe rOJ[bI pftj[
HCCJIeZ[OBaTeJIeH B pa3HbIX CTpaHaX (~)OpMyJIHpyIOT B TOM xJIH HHOM BH~O poAcTBex-
xbie aa~[a~fH. J~ocl'aTOUxo xalloMxxTb o pa6o'rax Weiss (1947), Tylor (1939, 1948),
?ICyxosa-Bepex{xxI{osa (1944) H Bslaosa (1953), 06 HccJleAoxaxllxx I'axlel{a (9955)
xo BoHpocaM HMMyxoJlorHUecxoro c6Jlxx{exrlft xpli Bere'raTHBxoil rx6plijjH3agLIH.
IIpHBej[eM xJIJIIOC'rpauxN IIa pa6oT xalxeH Jla6opa'ropHH.
ToKxx (19556) y6e~HJICII B rlpaso're aBTOpos, yTBep>K~asxlllx, ~ITO H B npoljecce
osorexeaa y rHAp Bo BpeMexxoM ftHUxxxe paabirpblBaloTCSI c~arol[HTapxbie peal{IjHx.
Oj[HH KJIOTKH (~aPOIjxTHpyIOT jjpyPlle. ]J' CTb OCHOBaHHft CLIHTaTb, '1T0 (~)OpMHpOBBHIIe
ftHlja rxZjpbI HB xMeJiO 6bI MBCTa 6e3 (~arOLjI3TapxblX peaKIjiIH.
I~y3bMHHa (9955) x Apyrxe B HalIIeI3 JIa6OpaTOpI3H IIpOBOJ[ftT HCC-JIeT~OBaH11R O 3Ha-
Llexxll (~arOljHTapHbIX peaKIjHH x IIpOIjeCCOB BOCIIaJIexHft B XO;je HOpMdJlbxOll
perexepauHH.
3b16xHa B HaHIex JIa6OpaTOpxx, OCIIOBbIBaftCb Ha yKa3aHHbIX Bb1IIIe pa6OTal
TOKHxa H ~xJIaTOBOLI (19536, B) 06 aHTH6HOTHYOCKIIX CBOI3CTBBX HIIIj MJIeKO-
ITHTaIOI1jHX H 1KHj[KOCTx IIOJIOCTx 6JIacTOr[xcTbl, xposeJla MOp(~)OJIO1'r1LICCKHe IIa6JII0-
.[eHxx HaJj HMIIJIaHTaIjIIOH 6JI8CTOIjHCT (KpbICbI) B CTeHKy MATT{Lf. 1~aK N.3BeCTHO,
HMeeTCft 6oJibiuOe KOJIHileCTBO xpeBOCXOJ>;HI~X rxCTOJ[OrH~IOCKIIX pa6OT lU) 9TOM}'
BOITpOCy, OJ~HaKO H Zj0 CIIX HOp OCTaeTCft MHOTO HeftCHOI'O B ftBJIeHHHX HMHJIaHTauHx.
c3b161LHa V6eJ~HJIBCb, BO IlepBblX, B TOM, 9T0 B xpOljeCCBX ITMI1JlaH1'a1jHx xMOIOT
6OJIbITIOe 3Ha~IeHxe (~arOljxTapHble peaKUHx, a BO BTOpbI?X, B TOM, i1T0 Te ?ICe aHTH-
6xOTIitIeCICxO CBOIICTBa HHIj, KOTOpble MO)I{HO paCCMBTpHBBTb KdI{ IIOTCHI[HaJIbHO
HMMyHOJIOI'HileCKHe, COBepIIIeHHO xeO6XOJ>HMbI JJ,JIft xpOIjeCCOB (~OpMUO6pa3OB8HIIA:
sbrAenftioH[Hecft sapoRbrmeM aHTH6HOTx~ecKlie sem~ecTBa, xapftAy c. ;~pyrLrMN c~aL:TO-
paMH, o6ecnevxsaioT xHSHC snHTeJIHx x HMHJIaxTauxio aapoAbima.
5. Eeponeuc~cuu zxu,~,eu u B. pluton
C[pxseReM exje ouHx HpHMep xayuxo-xccne~osaTeJlbcKxx rroxcKUS B xusoM
HaxpasJrexHH. BeTepllHapHft H McAHuHxa He MoryT xe HxTepecosaTbcft sM6pxonorH-
uecKOii npo6JleMOii HMMyxx're'ra aapoRblHlex. TaK yx{e uHTHposaxxaft pa6oTa I4opoT-
KoBO~I HpeAcTaBJifteT HH'repec ~JIft nTNueBO~cTBa.
~M6pxo~ror llpNes>KeBa (1955) s xaruem Jla6opaTOpNH aaHHTepecoBaJZacb so-
xpocoM: HoueMy 6aKTepHaJibxoe sa6oJresaxxe nueJlbl-espone>3cxxil rxHJleu - npLi-
y'pO~T0H0 K OHpe~eJIeHHb1M CTaJjHHM JIxtIIIHOLIHOTO pa3BHTHH, a I1M8HHO 1{ 3-M}' 11 4-M\'
,.[H1IM? tIOM O6eCHeLIIIBaeTCH pe3xCT0HTHOCTb TKBHeii JIH~IHHOK 1 II 2 jjH(`Ii, a TaKiL{C
J II 6 J~HOH pa3BHTHft~
IJ,px HH'beKIjxII BO36yjjxTBJIA 6OJIe3HH - B. p1Llj,Ox-B TKaxH ZjByXJjHeBH6IX JIHl3HHOK
IIpOHCXOjjHT 6bICTpOe yHx9TO5I{eHxe 6aI{TepxaJIbHbIX KJIOTOK. e~TO He Ha6J[IOjjaeTl',ft
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
y 3-X H 4-x ~HeBxbiX .nHUHxox. J~oxaaaxa paa~H~HaH ~arouHTapxaH asTHSxocTb
Txaxeii xHUHHOis pasBOro BoapacTa.
HBJIEHHH T. H. BCOBMECTIIMOCTH> 1I KHECOBMECTHMOCTH> TKaHEH, pEPHCTpHpyEM6IC
B pa3JIH~IHbIX OIIbITaX TpaHCHJIaHTaL~HH, IIEpECaJ~SH TICaHEH H OpraHOB, COBCpIIICIIIIO
3aiCOHHO CBH3bIBaIOTCH HCCJIEJjOBBTEJIHMH ~HaHpHMEp, TaHIEA~ C HMMyHOdIOTH~IECICHMiI
CBOHCTBBMH TKaHEH H OpraHH3MOB. ~JIH OrO'bFICHEHHFI 3THX HBJIEHHI3 JIO1'HiTHO IIpH-
RJIEI TICaAEH. B 3TOH CBH3H BbIT~aIOIIjHHCH HHTEpEC HpCj~CTaB-
JIHIOT HpCBOCXOj~HbIE HCCJIEJ[OBBHH)I I`aIHEIia ~1~JJ~, pa3pal)O'raBIHErO OpVIrHHaJIbNbIH
CHOCO6 3M~pHOHa.7IbHOI'O Ilapa~HO3a }~ IITHI~: CpaL[jHBaE'CCA aJIJIaHTOXOpIIOH 3ap0-
J[bIIIIEH ~~% Iiyp H f~a3aHOB rla g-12-II J~EHb HHKV~aI[HH, y HHjjEEK 11 VTOIS Ha
12-1v ReHb). OcyB~ecTBarex Ilapa~iHOa Me;irRy hypaMH paaxbix Hopo,~ H ME,Ie;iy
pa3HbrML1 BHJ~aMH IITHI~.
MbI MO?KCM JIHIIIb BCEI~EJIO IIpHCOEJ[HAHTbCH KO B3rJIHJ[aM raHlElca Aa BOIIpOCbr
HMMyHOJIOPH~iECKOPO C~OJIriil{EHHH. BCE j[OTBJffi pa6OT TaHIOIia I[pC~[CTaBdIHIOT 1ICICJIIOiIH-
TE7IbHbIII IIHTEpEC j[JIH HaC, 3aHIITbIX HpO~O7IEMOH H:irMyHHTETa 3MhpHOHOB.
TaIC, j[OHa3aH0, 9T0 Hprl ME)rCBHJ[OBbIX IIapa~HO3aX tIaCTH9HOE COJIHSIiEHHC AaOJIIO-
j(aETCR ISBIi IIpOTHB HapTHEpa, TaIC H JIpyrHX HHJjrIBHJ[OB TOTO iiCE BHJ~a. y Kyp, pa3-
BHBBBIIIHXCH B 3MOpHOHaJIbHOM Hapa~HO3E C HHj(EHLCOH, OOpa3OB8HHC HMMyHIIbIk
arrTIIOTHHHHOB HOCJIE HMMyAH3aI~HH 3pHTpOI[IITaMH HAJ~CHICIi 3HaiIHTEJIbHO CHLI-
?IiaCTCH.
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O~pa3HbIX, B TOM ~IHC7IE HMMVHOJIOTHLIECiCHX 1~1ETOJIHIC, HECOMHEHHO 3ai1HTEpCCyIO1'
HlilpoxHe I;pyrH ~HOJIOTOB paaxbiX crieuilanbHOCTeK.
c~THX HpHMEpOB J~OCTaTO9H0, iITOhbi CO3J~aTb HEKOTOpOE IIpEJjCTaBJIEHHE O HaHpaB-
7IEHHH paOOT B 0~7IaCTH HMMyHHTETa 3M6pHOHOB. MbI CJIEJIyEM 3aBET8M i~1EiIHHICOBa.
~OrHKa HCC7iOj[OBBHHH HpHBEJIa MEtIHHICOBa OT 3MhpHOJIOrHH K HMMyHOJIOrHH H MCJ[H-
I~HHE. IIO MHOI'HM HpH9HH8M ME9HHICOB, K CO1ICa~IEIIffiO, HE BO3BpaTHJICH IC 3M~pH0-
JIOPHH, K HB7IEHHHM HMMyHHTETa }~ 3apOJ~bIIIIErI.
MbI IIO3BO7IHM CE~E 3arCOH~IHTb HaIII}~ xpaTICyxI CTaTbIO Bbipali{EHHEM H8J(ESIC~[bI
9T0 B pa3pa~OTKE HayHAOPO H3CJIEJ~HH ~. ~. 1~E~IHHISOBa B BOHpOCaX HMMyHH-
TETa 3MCpHOHOR, HEO6X0~[HMOrI B HHTEpECaX 3M~OpHOJIOrHH, MffiSpO~HOJIOTHH, HMMyHO-
JIOPHH H J~pVrHX CHEI~HaJIbHbIX BETBEH 6HO7iOTH9CCKHX, ME~HI~HIICICHX H BETEpHHap-
HbIX 3H8HHYI, - HaHIE HaIIpaBJIEHHE pa6OTbI BCTpETHT HE TOTIbKO HEH36E5AHbIr1,
COHyTCTRyIOII[HII BCHKOH HOBOH HpOC)JIEME CICEHTHIjH3M, HO H OJ~O6pCHHE TEX, KTO
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
CLIHTaeT, LITO HMMyHO7IOPYIH J~O7IH{Ha ~ObITb TOCHO CBH3aHa C 3M6pHOJIOrIieH II 3BOJIIO-
IjIIOHHOYi TOOpIIe{i.
7,~ c~aJIOTOM ycneIIIHOYI paapa6o'rxH HOBOi3 npO6JIeMbI HBJIHOTCH IICTOpIILIeCKI{H M0T0~
Y1JIbH ~TIbIItIa Me*LHIIKOBa.
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3M6pnOTIOTIIH pa3pa6aTbiBaTb HOByIO IIpO~7IeMy - IIMMvHi3T0T 3apOJjbIIIIen. I7aKOBbi
) 3MOpIIOHOB pa3TIH~IHbIX ?KHBOTHbiX? Ha I{aKHX CTa,TjHxX paaBllTHfl
)ICHBOTHbIX H i{eJIOBOKa BO3HIIKaIOT (S)arOljIITapHble peaKIjI3H H CO3j[aeTCH BO3MOIKHOCTI,
HBJIeHIIH BOCHa7ICHHH? H~ap KBKHX CTaJjHHX pa3BHTHx :IapOJ[bIIIIEIi BO3HHKaeT aHTII-
reHHaH peaKTI3BHOCTb? llaKOBbI aHTIIhIIOTn~IeCKIIe CBOIICTBa TKBIIeII 3apOjjbIIIIeH?
2. ~iaK B XOj[e 3BO7IIOIjIIH OpraHII3MOB pa3JrHYHble HMMVHOJIOTItLIeCKHe CBOnCTBa
BO3HIIKaJIH H pa3BYIBaJIHCb Ha 6a3e ~OJIee O~)LIjIIX (~yHKIjIIH ~HaIIpIIMep, (~arOu{iTap-
Hble peaKIjIIH BO3HIIKJII7 Ha 6a3e BHyTpHKJIeTO9HOT0 IIIIIIjeBapeHHA~, T8K H B OHTO-
P8He3e - BO3HHKHOBOHHe II CMOHa pa3JIHLIHbIX 3aIIjIITHbIX CBOHCTB He MOryT ~blTb
HB7IeHHHMII, OCIOCOhJIeHHbIMII OT npOljeCCOB 3M6pHOHaJIbHOPO paaBHTIIH. Bonpocbi
HMMyHHTOTa 3MCpIIOHOB He MOryT pa3peIIIaTbCH Oj[HOCTOpOHHe
KpyIIHbiX HHOpOJjHbIX LIaCTHIj, (~OpMIIpOBBHHe Me3eHXHM8TO3HOiI KaIICyJIbI BOKpyl'
HHOpO~HbIX TeJI. p,OHJjya JjaeT OnHCBHIIe nOCJIOJjOB8T0JIbHbIX MOp(~)O7IOrHtIeCI{IiX
KapTIIH, 3KCHepHM8HTa7IbH0 BbI3B8HHbIX HB7IeHHH BOCIIaneHHH Ha pa3HbIX CTaJjHHx
pa3BIITIIH 3apOZjbIIIIa. ).
4. ~CC7Iej[OBBHHHMII IlOpOTKOBOH K Z[pyrHMH OC IIMMyHOJIOPHtIeCKOM 3HaYeHHI1
O~OJIOLIeK HIIIj )ICHBOTHbIX BbIHB7IeH pHR HOBbIX IIHTepeCHbIX (~aICTOB.
~aICTepIIL[HJjHble, IIpOTHCTOIjII~[Hble K (~yHTHIjHJ~Hble CBOIICTBa 6eJiKOBOiI OOOJIO9KIi
KypHHOTO HHL[a He COBIIaZjaIOT C TaKOBbIMH CROHCTBBMII .
B xo~e paaBIITHtI aapoRblIIla aHTIi6HOTHYecKHe cBOHCTBa 6enKOBOii o6oJioYi{{r
HaMexHloTCH.
B IIOJIHOM COOTBCTCTBIIII C jjaHHbIMII raIIIKOBOI3, TIOKOpHOH, ParO3IIHOII H Rp. ,
yCTBHOBHBIIIIIX, iITO C 12 jjHH HHKyCaIjIIH 6eJioi{ CMeIIIHBaeTCH C aMHHOTIILIeCKO{i
1ICIIJjKOCTbIO K 3arJIaTbIBaeTCH 3apOJjbIIIIeM, - KOpOTKOBa O6Hapy)iCIIJIa yCI3JIeHIIC
IC 3TOMy BpeMOHH II aHTHCHOTHtIeCKHX CBOIICTB aMHIIOTIITIOCKOH }KHJjKOCTn.
5. TOKIIH N ~IIJIaTOBa y6eAIIJrHCb B 6aKTepLluNunbix csoKC'rBax nIIlj nlJrexonHTa-
toll[Hx Ro nx HMIIJiaHTauIIII B cTenxy MaTKII, a TaKx{e B 6aKTepHuNAHbIx csoHCTBas
>I{IIAKOCTII IIoJ1ocTH 6alac'roljllcTbi.
6. 3b16nna Ha ocxosaxIIII csollx rlicTOJiorHYecKHx IIccJreAosaxHH VTBepx{AaeT,
~ITO Te x{e aHTII6IIOTIIYecKHe csoiicTBa HIIIj H 6JtacTOLjHCTbi IIMeIOT c~opMOO6pasoBa-
TeJibnoe :IHaYexlle, o6ycJtoBJIHBax, HapHRy c 't[pyrIIMH c~)aKTOpaMH, JIIIaIic anHTeTrnH
MaTKH. EIO x{e IIayYenbi c~arouIITapnbie peaKljIIII, pa3birpblBaIOLi[HecH B xone npo-
ueccoB IIMnJraHTaIjHII.
7. TOKIIH IIoRTBepAIIJt Aaxxbie IIpex{HHx aBTOpoB o anaYeHHH c~aroljliTapHbIX
peaxljllli B IIpoljeccax osorexeaa y rIIRp.
$. ~CCJIe~[OBBHIIH I'aiIIexa H j[pyrYlX aBTOpOB IIO 3KCIIepIIMeHTaJIbHOMV
IIapa6HOSy aMOpllonoB HTHIj npeRc'raBJrHIOT 6OJIbIII0I3 o6IIje6HOnorHYecitllK HHTepec
H IIHTepeC B CBH3I3 C IIpO6JIeMOLI HMMyHIITOTa 3apOJjbIIIIEH.
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
~InTepaT ypa
A .6 e T I4 fG fl H, Fi, I',: I/IMMyHOJIO PII~ig(;Hne peaKl(411i C 6ecno anoao~InLlx ll XOJ10J.~H0 KpOIIH6IX
nossollo~Ixtirx. ~[oxTOp. AllccepT. 9pei3ax 1952.
B fl 3 O B, (]. ~.: HCHOTOpble J.[aHHble n0 n3yi[eHnIO aHTl11'eHH bIX CBO ~ICTB ~M6pnOHaJIbHbIX THaHe~I,
Iilo.ns. ahcrt. fiuo.n. Ii Me;1. S, 1953.
I' a III e x, M.: Bonpocbl BeraTaTnBUOti rn6pnAllaaglau n nepecauxll TtcaHl~ y ~renaloreponx~,Ix )IfN-
noTUblx. 5I{ypxaz o6u~e~ 6voriorlall 16, (5), 1955.
Pam I< o s a, B., II o x o p a a n, 3.: IIuTaxxc aapo~rnua =Iepes poT. 1101. biol. (Praha)
1:113, 1955.
I' II p ~~~ a x o s a, ?~. H.: O6 nsMeneun>ix fiaxTepi~u~t~Hhlx csoiccTS xaTypa.uexoro 6enl:a II ~KSO-
quMa xypHxoro aiaga ~ xoile IIxHy6alju>a. BAH CCCP, 68, (6), 1949.
J~ o x R y a, A. Ii.: ~arognTapHau a Bocnan~Te~bxaa peal.q~K xa paaxlilx aTanax onTOrexesa.
9xcuepnMexThl as xypnllorv[ sapoR~Ime. J~AH CCCP, 104, (6), 1955.
f~ ~' ISO R - B e p P. Ni H ll H O II, H, H.: I/I, I~. ~1eRHnKOn !( ENO ZO Pn40CHne Oe HOIILI WMMyHO-
noriah, yCII, coBp, 61f0~~. 18, (1 ), 1944.
3 u ~~ t, fi e p, JI. A.: OCHOI3bl uMMya>1TeTa. Mocl:ria 1948.
Iti o p o T x o n a, P. II? II p II e a ax e s a, .?I. C.: Bonpocvl IIMMyxIITeTa an26puoxoB. BecTarnx
JIl'Y, 7, 1952.
Ii o p o z x o 13 a, t'. IL: O Toxcu~IecKIIx caorlcTBax eFie~~xa> II xypnuoro n0ua.
RAH CCCP, 92, (1 ), 1953.
Ii 0 p O T IC O B a, r. II.: AHTm)iIOTN9eCK41 e. CBOI~CTBa 6e.IKOB01-i 060JI09 kn HypNHOPO 3apOJ~bI IIIa
r;aK ~axTOp i1MMyxnTe~ra. BecTxnlc ~II'~' 3, 1956.
Ii y 3 h M II H a, I', ~.: I30CIIa:IeH41e BO B3pOC~"IbIX CePMeHTax, 30He pOCTa II pePCHCpaTA. BAH
CCCP 100, (4), 1955.
II ~ YI e 3 NC e B a, ~. C.: Pp:II> n4CS1l1HbIX MBTOK B paCIIpOCTpaHeH14M QBIIOTIC i$CKO PO PH N~IbI~a,
Ihle~osoT~crao, (11 ), 1955.
'P o x II a, ti. 11.: yIMMyxuTeT aapoablmeK. ~IexNxrpa;5 1955a.
T o x ~I x, ICI. I4.: Hertc[Ir,Ie nollpochl oBOreaeaa IIydra oligactis. RAH CCCP 102, (1 ), 1955b.
T O IC K H. ~. II. ~ ~ K :I a T O B a, A. T.: I~OBbIC' Aa HHGIe J~.IIH Cy51SJ{('HIIft 0 ~iHa'ICIIMPI aMHMOTI4-
=IecxoH SrcllAxocTll M~elronxTalou~Hx. BAH CCCP, 91, (3), 1953a.
T o x x x, P. II., ~ x rI ;~ m o ~ ~~, A. P.: O 6aK~~epn1lH~xvlx ci3oucTBax anq xpo.allxa. ,AAIi
CCCP, 91, (4), 19536.
T o x H rt, F, II., ~ n .r a z o I3 a, A. F.: O ;~cII;1KOCTU ilosocmx 6,rracmo1lucT~I. J~AII CCCP,
90, 5, 19536.
T o x II x, Ii. II., ~ II .n a m o s a, A. P.: F9i1go hpoalxxa II ~a xTepz2u (Mamepila~Ibl If npo6.neMe I~MMy-
xml~eTa aM6pr~oxoa). ~~Ix, TIO TCXHH9eCHNn?
npH9HHaM: KO}Ifa 3J1,UCb TOHbHIe, yeM Ha upyPH% yaCTAX TCJta, - a BO-BTOpbIX, nOTOMy, iITO IIp11
pa3JIH9IiftX THITOB iuep CT1I y~06Hfe np OC ~(J.[H'Ib Cy ubGy TpaxCnJlaHTaTa, BbIOp HTyFO KOH{~' MbI Onpbl-
CKNBaJIN 1 ?~o paCT BOIOM nIOKBIIHa, HOTObI CICa7IbnCJIeM Cpe3aJIH TOHHyIO IIOJIOCKy KOIICH H N3 Hee
H03liH-IIIaMId BbIpe3aJIH OTJjeJIbHbIC 7paHCHJIaHTaTbI pa3MepaMH HpH~JIHSHTe.AbHO B 0,5 I,~ CM_
MbI He~eCaiKHBaJIH TpaHCnJIaHTaTbI Ha CHHHKH ~n0 C'[OpOHBM n03HOH0`1H11Ka H xeCKOJIbI{0 HHHCe
7IOnaTOK~. ~~JIH Ka}I{~OTO TpaHCnJIaHTaTa HpHPOTORJIftJIOCb dIOilie, HpH~IJ1H3HTeJIbHO OTBe~ialOT1~eP.
8My n0 ~a3Me~aM. Cpe3blBaft KOHCy J~JIft npHPOT013JIeHHft IOiKa, MbI HOnb30BaJIHCb TCMH iKG McTO-
ZjaMII, KaK Ii Hp HPOTOBJIftft TpaHCn7IaHTaTbI H3 HO}KH yXa, I~aHLJjOMy NiHBOTHOMy HepeCaH{HBaJIOCb
3 T axCHJIaHTaTa: CO ~CT BeHHbI )'I, OT MBTepH H OT eP0 6JIHiIHe qa; y TpO~HIi JjCdIaJIHCb !t nep CCaJjKN_
CO~TBCHHOLI K01lLH, OT MBTepH HOT OCTaJIbHbIX uByx napTHepOB,
II.iragexTbl Bcex 6.nHSxegos ~HKCHpo]IanHCb B ~]opMO.-Ie. Ec.nH 6biBaJIO xailuexo cpan~exHe
XOIiIIOHOB, ME'.CTO CpalIjeHNft HpORCHHJIOCb nyTf.M npOBOJ{ICH 9epeo CnHpT B ~eH~OJI,
P P32~.R~ b1Y1 Q IYd b1
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H{eHIIH IIO OTHOIIIeAHIO IS KO?I{C IIapTHCpa. 5 IIap 6JIL13HCLjOB H3 3THX ~ ~bIJIO pa3H0-
Hoxblx, 4-ouHHaxosoro Hoa~a. ToMOTpancH,rraxTaTbl xali oT MaTICH, Tax H oT BTOporo
IIa 6~IHaxeljos Bo Bcex c~Iyuaxx BbI~ICHBaTIH McHbHIe 18 uxeil. I~Ia xoxTpo~Ibxbrx
aBTOTpaxcllnaHTaTOB 3 xe HpHxftHHCb. Y 3 nap xc ~b1~o cpalljexllH xopxoxa, y 6 Hap
xa6nloua~HCb cpaHjexHH, xo oTxeTnHSO aaMeTxble coycTbH cocyuoB B xHx Hal?Iuexb2
HQ ~bIJIII.
y HCCJIejjOBaBIIIeIICH HBMH TpOHHH BCC 3 HPHCHKa HaxO;I,H7IHCb B 067IjCH 060JI09ICe.
B CpaHjeAHHx XOpHOHOB JjByX H3 xHX 6bIJIH OTileT~IHBO 3aMCTHbI COCyjjHCTbIC aHaCTO-
M03bI~ Tax iITO 3jjeCb HMeJICH PebiOXOpHaJIbHbIH THH 3MOpHOHaJIbHOI'O IlapaOH03a.
B xepeXOJjHOII OCJIaCTH K XOpHOH y' TpeTberO HTHCHHa COyCTbH COCyuOB HaHueHb7
He FbIJ[H~ TaK LITO 3jjCCb 6bIdI HpeJjCTaBJIeH ICOHTaKTHb11I THH 3M~pHOHaJIbHOTO IIapa-
6N03a. B TpOIIHe 6bIJI0 2 OBeTIKII H OuHH 6apaIIIeIC. y OuHOYI H3 OBeTIeI^ Aa67II0ua7IOCb
B3aHMHOe HMMyHOJIOPHiICCKOe CGJIH?IieAHe C hapaIIIICOM: K05ICHble POMOTpaHCxJIaHTBTbI
UT C6JIH5ICeHHOI'O HapTHepa COXpaHHIOTCH y HHX B XOpOITIeM COCTOHHHH u0 JjHH HaHH-
CBHHH HBCTOHIIjCII CTaTbH, 'I. e. B TCTICHHC 11O J~HCI4. BCC OCTaJIbHhIC TOMOTpaHCHJIaH-
TaTbI - IeaIi y OhOHX C~JIH>ISCHIIbIX 1ICHBOTHbIX, Tali N V TpeTbeTO H~3 hJIx3HCIjOB -
IIOjjBepPJIIICb jjeCTpyKIjHH HC II0311ie 18-I'O JjHH, Icax y OCTaJIbHbIx xojjOIIbITHbIX
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BoapacT Bl~i~ISHBalINe Tpaxcn.naxTaTOs
H Bec Bo BpeMft ---.
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-I- Tpaxcn~axTaT 7KHJI Bo Bpe'vlft HauHCaxHft cmambH.
- Tpaxcn.naxTaT pa3p,yHraeTCft xe noaAxee 18-ro jjHfl,
TpaxcnsaxTaT Ha 18-brYI ~jexb B cpaBxHTesbxo xoponm~I cOCTOftHII4l. ]Ia 27-r~ ~[exb py~ eII.
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
?KxBOTHb1X. T07IbK0 y 6apaHlKa x3 TpoiIHII rOMOTpaHCnJIaHTaT OT MaTKx Ha 18-bIYi JjOHb
~bIJI OHjC B CpaBHHTeTIbHO XOpOnIOM COCTOFIHxx, HO Ha 27-x ~OHb OT Hero OCT8Ba7ICfl
yaKO TOJIbKO py~i0u. ABTOTpaHCnJIaHTaTbI npx5Kx7Ix y BCOX TpOxX IIrHHT II3 TpOI[Iill.
;~juc~~ccuu
Anderson c corp. (1951) nblTa~Incb ncno~Ib3osaTb nepeca~ll{y Kox{Il nalx Rxarxo-
cTxl{x oRxoHxvxocTx xnx ~ByxnvxocTx y 6nxaxeuoB poraTOro cI{oTa, xo BBxAy
3Ha=IxTOJIbHOii =IaCTOTbI CJIy=IaOB IIMM}~HOJIOrn=IOCKOPO C6JIIi}ICOHIIx MeiICJj}~ ABy-
fII3BHbIMx Cr)JIx3HEIjaMx 3T0 OKa3a7IOCb xeB03MOi1CHbIM. Lampkln (19J3) Ha OCHOBe
CBOHX J~aHHbIX npej~xOJlaraJl, =ITO 3TOT KpHTOpnx MOi}CHO 6yReT xcnonbaosaTb
y xrHxT-hJIn3HOI~OB. Lampkln OCyII[OCTBxJI B3axMHyIO rOMOTpaHCI1JIaHTaIjxIO KO>I{x
TOJIbKO y JzByX Ilap ATHIIT-~JIII3HOI~OB. y j[Byxx=IHbIX TOJIHT-6JIH3H0I[OB HahJIIOJ~aeTCA
yCTOI3=IxBOe npliiKxB7IeHHe KO?ICHOTO TpaHCnJIaHTBTa OT napTHOpa I[pxrOTln3xTeJIbHO
s 90% Bcex c~Iy~aeB (Billingham c corp. 1952). Tax Kax Lamkin xe xa6~IloAan
ycTOil~xsoro npxal{xBnexnx Tpaxcn~IaxTaTa oT napTllepa xn y ouxoro na csoxx
HPHHT-6JIx3HeuOB, TO eMy npx CpaBHOHxx C yCJIOBxIIMx y KpynHOPO pOraTOPO CKOTa
ICa3a7IOCb, =ITO CPO MaTepxaJla ;jOCT8T0=iH0 j[JIFi :IaKJII09eHxx, iITO xMMyHO7IOrx9eCKOe
C~7iNH{eHxe y OBe=IbxX ~JIx3HeuOB, BOpoxTHO, He CVII(eCTByOT. ~exCTBIITeJIbHO,
y OBOU nJIaI[eHTapHble aHaCTOM03bI BCTpO=IaIOTCH rOpa3J>;O pex{e, =IOM y KpynHOTO
poraTOro cxoTa. lZpx aTOM y Kpynxoro poraTOro cxoTa npeo6naltaloT c~Iy~ax 6epe-
MexxocTx oRxHM n~IO~oM, a ec~Ix yx{ 6b1BaeT uBOiixx, To B 85% c~IyuaeB (IleTCxoii
1955a) aRecb coaRaeTCx BaallMxax reMOxopxa~Ibxax cBHSb. NanpoTxB, y oseu Mxoro-
naloRxe scTpe~aeTCx ~acTO, a reMOxopxa~Ibxoe coenxxexxe Me>I{Ay aapo~bllHaMx -
Tonbxo B 8,6% c~Iy=IaeB. ILIMNj[T (9955) oTMe=IaeT, =I~'o y ;KBaxxblx oAxon~IOAxe xe
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
collposoax~,aeTCSi HpHCHOCO6neHKeM, Ko'ropoe npe~mecTSyeT rzoaHllhHr)neHI11o co-
C}~~[I1CTb1X BHaCTOM030B; ICI H81Ip0'CIIB, ('.paBHIITEJIbHO BbICO1C00 MHOl'OIIJIOJ[I1C y?IC@
CiIH3aH0 L 9TNM HBJI0Hii0DI II~IICIIOCOOJIE?H14FI. I~ICXO~[H II3 IICCJIO,'[OBaHNII XOp1IOH8,
P1IC. ~~ 3. CT~)~rKTy~~I IIp LIHHBLII@POCH KOiIi EiO PO PO MOTpaiICIIJ1aI1TaTa C yIlIHO~i ~aKOBFiHbI 1R S1tU ~2~
H C II~)IIIIO J-~HHT011 iC07ftH0~[ CICSI7J~IC0 ~4 ~3~.
r
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,jBy'Mfl ~ByAYI9IIbIMi1 3ajJOJ~hIIIIflMII V OBII,II BCTp~9aIOTCH C~BBHY[T~71bA0 pl;J[IfO. 1SCH11~, 9T0 B 3TOFI I'pyIIl[0 IIe ~bIJIO O~jHOH-
I~LiIHbIX 6JI1i3H0IjOB. ~TICpbITII~ StOfR70IIt.-8 H HaIII MflT0pN8JI IIOICa3bIB8H)T, TiTO ~IBCTOTa
CJIy~IaOB IIMMyHOJIOPHY~CICOPO C~JIII?K~HIIfI V OBCI[ IIpH~JIII3H'1'CJIbHO OTB~98CT TIflCTOTC
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CyIIjOCTBOBaTb J~Oi4a3y0MaH XI~MOPa KpOBII~ H T0M H0 M0H0C MOiiiOT Ha~JIIOJ[RTbCH
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
xMMyHOJIOTH=ieCKOe C6nx1K8Hxe McHCJ~y xapTHepaMx (raBleK, I'pa6a 19JJ). ~aHHble
OTHOCHTenbHO nMMyH07IOrxHeCKOPO CCnII}IfexxR y uenosexa MOlIiHO 1I03TOMy ROny-
yxTb TOnbKO C IIOMOIIjb10 nepeCaj[Iix KO?Kx. HO y =IenOBeYeCKHX rUnxaHel[OB 3T01'
Oxb1T He IIPOxaBOJjHnCR B TaKIIX pa3MepaX, =ITOC)bI MO}xH0 6bIn0 Z[enaTb xalclte-
xx6yRb oxoxuaTenbxble BbIBO~jbI (Rogers, Allen 1955). JTOMy Bollpocy cneRoxano
(r)bI IIOCBRH~aTb 6onb>IIe BHHMaHxR, TaIC K8K BII07IHe B03M0>fiHO, =ITO y f nH3HOI[OB
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=IaIOTCR IIOBbIIIIEHHOH CKOpOCTbIO pOCTa B CpaBHOHxH C TenRTBMIi-Hehnx3lIeuaMx.
PTO OTxpbITxe OTBe=IaeT JZaHHbIM HCCJIejjOBaHxI3 3M~pHOHanbHbIX napa6nOHTOB
y nTxu (Pamex 1953, 1955). LITO KacaezcR BnlixxxR napa6xuaa Ha o6paaosaxne nova
xapa6noxTOB Kpynxoro poraTOro clcoTa, To, xait xa>xeTCR, ecTecTBexxblH aM6pxo-
xanbxblil napa6xoa MexcRy aapoRbllIIaMx paaxoro nova o6biuxo npxBOAxT x c~px-
MapTxxxaMy y caMKx. Stormont xalHen xxNiepy y 6nxaxeuoB paaxoro nova. OBe~xa
lia aTOH napbi oxaaanacb 6ecnnouxoK. BcxpblTxe Hoxaaano, uTO npnvHxoH aRecb
RBnxeTCR c~)pxMapTxxnaM. Stormont BblcuxTan, uTO xacTOTa cny=IaeB 6ecnno;~xblx
Deco npx6nnanTealbxo oTBe~aeT npeAnonaraeMOMy KonI3~IecTBy Deco-c~pxMapTllxoB,
IIpOIiCXOjjRH~xX nX pa3HOHOnbIX xap ~nx3HeuOB, y KOTOpbIX B0:3HHKnIS COCyJjxCTble
aHaCTOM03bI. OT,[HaKO y KypxHbIX 3M6pnOHanbHbIX xapa6nOHTOB MbI He BcTpe~anH
IIx oRxoro cny=laR 6ecxnounR. ICI >xeHluxxa, y xoTOpoil 6bina Hailuexa xxMepa
)cpoBx, xe 6bina 6ecHnouxolz, xoTR BTOpoK xa 6nxaxeuoB 6bin ManbyxK.
Mbi xccneuosanx 9 nap osexbxx 6nxsxeuoB H ouxy Tpol~xlo. C;ocTOxxxe BaaliMxoro
c6nn>xexHR no oTxoHlexxlo x xo;KRoMy TpaxcnnaxTaTy napTxepa MbI RaBlnn y RByx
pa3HOHOnbIX RI'HRT x3 TpOI3Iix. ~.OCTORHxR C6n1i5xeHxR IIO OTHOHIeHxIO K x0)I{HOMy
TpaHCn7I8HT8Ty TpeTberO RPHBHKa H8 Ha6nIOj[anOCb. Y TpeTberO RI'HBHKa H3 TpOI3Hx
II y BCOX 9 nap ~nH3H0uOB TpaHCxnaHTaT OT xapTHepa paapymanCR Hep03 TaKOn xce
nepliou BpeMexn, K8K K TpaHCnnaHTBT OT MaTepx. Ha xopxoxax 6 nap 6nxaxeuoB
Ii y TpOHHx xaXOJ~IInxCb CpalueHHR, HO TOnbxO Me1KF[y xopIIOxaMx Rsyx RrxRT xa
TpoHHx o6paaoxanlicb oTUeTnIiBO aaMeTxble c.oycTbR cocyRoB.
~InTepaTypa
H .n n x e p, ~. R.: llapa6xoa. Bonbulax McANunxcxax axllxxnoneAnn 23, 1923.
I' a m e x, M.: BereTaTnaxax rl16pxRxaauxs N{unoTxbix nyTeM coeAuxexxx xposoo6pau~exxx
B Teyexxe aM6puoxanbxoro paasxTxx. LIcn. Bxonorxn 2:267, 1953.
t a III e x, M.: Bonpocbl BereTaTl-IBxo# ru6pxAxaagllu x nepecaRnx Txaxn y Ten?IOxposxbix
}ICxsoTxbix. ?Ifyppx, o6u;. 6no.n. 16 :405, 1955.
iI e T c x o #, II. r.: IIoxxTxe u Tunbl aMOplloxanbxoro napa6noaa. BAH GCGP 89:1123, 1953a.
II e T c x o #, II. r.: YCdIOBYIA BxyTpuyTpo6xoro paasxTUx Bos taurus, BbiablBalou~ue sisnexxe
I~pxMapTnxnaMa. J~AH GCGP 90:693, 1953b.
II e T c x o #, II, t.: 3ni6plloxa.nbxbie napa6noabl y I{oa iI oxen. TpyAbl I;xpoB. c.-x, nHCT. 9,
(21 ), 1953B.
II P, T C K O #, II. I'.: ~M6 nOxaJIbxble IIapa~n03bI n MHOrOn7IOJ~ne CeJIbCF{OX03x#CTBCHHbIX Ntn-
BOTHbIX. Tp. NHCT. MOp[~. >I{nB, uM. A. H. Gesepuesa 14:44, 1955a.
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II e z c x o H, II. P.: BaauMOOTxomexnn n.no~oB npu Mnorou.noi[ao~ 6epeM?unocTN II 3xa~icxxe
3TrIX B3anM00TH0menNli B N9MeHCHn}I M0p(~07I0Pn9eCHnX CI30LIC'fB 0pPaAN3Ma. TeBnCbl 1~0I(JIaj[0B
coseuSanxu amfipNO.noros n JIexnarpa~e, 1955F,,
IH M n j( T, r. A,: C? BpeMOHn K Cn0C0 ~e 0~pa30 BaHNA 3M~pIIOI~Ia ~bnbiX naparin03pB y KOI OBbI
n osgr,I. Tp. HxcT. Moplh, xsnB, nM. A. H. CeBe.pgesa 14:207, 1955.
Anderson, D., Billingham, R. E., Lampkin, G. H., Medawar, P. B.:
Heredity 5:379, 1951.
Billingham, R. E., Lampkin, G. H., Medawar, P. B., Williams, I1.:
Tolerance to Iomografts, Twin Diagnosis and the Free-martin Condition iu Cattle, Heredity
6:201, 1952.
B i 1 1 i n g h a m, R. E., Brent, L., Medawar, Y. B.: Actively Acquired Tolerance
of Foreign Cells, Nature 172:602, 1953.
Dunsford, I., Bowley, C. C., Hutchinson, A. M., Thorn ,son, J. S.,
Sanger, R., Race, P. R.: A Human Blood-grouil Chimera. Brit. ~ed. J. 11:81,
1953.
H as e k, M.: Vegetativni hybridisace iivo~ichu spojenim krevhich obchu v cmbryon5lnim
vyvoji. ~s. biologic 2:265, 1953.
H as e k, M., H r a b a, T.: Immunological Effects of Experimental Embryonal Parabiosis.
Nature 175:763, 1955.
Keller, K., T a n d l e r, I.: Tiber das Verhalten der Eihaute bei der Zwillingstrachtigkeit
des Rindes. Wien tierarztl. Monatschr. 3, 191f.
Lampkin, G. H.: Intolerance of Dizygotic Twin Lambs to Skin Iomografts. N~;ture
171:975, 1953.
L i 1 I i e, F.: The Free-martin: A Study of the Action of Sex Hormones in the I~'octal Life of
Cattle. J. Exp. Zool. 23, 1917.
Owen, R. D.: Immunogenetic Consequences of Vascular Anastomosis Between Bovine Twins.
Science 102:400, 19/i5,
R o t e r m u n d, H.: Tierarztl. IIochsch. Hannover, 1929 (Cit. Stormont.)
Rogers, B. O., A 1 1 e n, G.: Intolerance of Dizygotic Human Twins to Reciprocal Skin
Homografts. Science 122 :158, 1955.
Stormont, C., Weir, W. C., Lane, L. I,.: Erythrocyte Mosaicism in a Pair of Sheep
Twins. Science 118:695, 1953.
Immunological Approximation of Sheep Triplets, Natural
Embryonic Parabionts
Prior to the attainment of experimental immunological approximation by embryo-
nic parabiosis (Hasek 1953) and by intra-embryonal injection (Billingham, Brent.
~'~Iedawar 1953), the natural occurrence of this process of adaptation in cattle dizy-
gotic twins, in which blood-circulation had become associated during intrauterine
development (Owen 1945), was already known. In sheep twins, on the hand, chorial
anastomoses are relatively rare. They were found by Petskoj in 8.6% of cases.
As compared with the anastomoses in cattle embryos, where they are often of
a considerable size (magistral form), the anastomoses in sheep have the
appearance of a capillary network (i. e. diffuse form). Stormont (1953) while attempt-
ing to determine whether blood chimerae analogous to the chimera in the calf, occur
in sheep, found this to be the case in one pair out of 26 twins. Lampkin (1953) trans-
planted skin grafts between four sheep twins, but all however, were, destroyed
during 7-14 days. In this investigation the occurrence of immunological approxi-
mation was determined on more numerous material using skin grafts.
In none of the nine pairs of sheep twins was immwiological approximation
of one twin found to the skin of the other. The survival of skin homotransplants from
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the mother as well as from the twin was in all cases shorter then 18 days. Three of the
control autotransplants did not heal. The choria of three pairs were independent of
each other, in six pairs the choria were grown together, without, however, any
apparent blood-vessel anastomosis being found.
In the case of the triplets observed, all three lambs were inside common mem-
branes. There was an evident blood-vessel anastomosis in the connected choria of two
of the lambs. Two of the lambs are of female sex, the third is male. Mutual immunolog-
ical approximation was found between one of the female lambs and the male: skin
homotransplants ofthe tolerant triplet survived in good condition to the time of publi-
cation i.e. 110 days. All other homotransplants in the approximated animals as well
as in the remaining triplet were destroyed by the 18th day as in the other experi-
mental animals, with the exception of the approximated male-lamb. Here the skin
graft from the mother was still in a relatively good condition on the 18th day, but only
a scar was left of it by the 27th day. Autotransplants healed well in all the triplets.
Anderson et al. (1951) intended to use skin grafts for the diagnosis of zygosity
in cattle twins. It was not, however, possible on account of frequent immunological
tolerance between dizygotic twins. Lampkin (1953) assumed on the basis of his own
results, that it might be possible to make use of skin grafts in the case of sheep twins.
His assertion, that immunological approximation in sheep dizygotic twins is highly
improbable has been shown, however, to be premature. Lampkin grafted skin in two
pairs of sheep twins only. In cattle dizygotic twins permanent survival of the skin
graft is present in about 90% of animals (Billingham et al. 1952). As Lampkin did
not observe permanent healing of the partner's skin graft in any of the twins, it
seemed to him, in comparison with cattle, that his material was sufficient to vouchsafe
the conclusion that immunological approximation is probably not present in sheep
twins. In our material approximation was found in animals from a single multiple
litter. As the approximated individuals were of a different sex and as the survival
of the skin graft from the other twin was in no other case observed, it is possible to
assume that there were no mono-ovular twins in the group. The finding of
Stormont as well as our data indicate that the frequency of immunological
approximation in sheep corresponds approximately to the occurrence of blood-vessel
anastomoses between the choria of sheep twins, i. e. 5-10%. It is not, therefore,
possible to make use of skin grafting for the determination of mono and biovular
twins in sheep.
The blood chimera has also been found in man (Dunsford et al. 1954), but it
seems that it is still more rare than in sheep. As far as the frequency of immunolog-
ical approximation in human biovular twins is concerned, it is not possible to draw
conclusions from Dunsford's data. In chicken embryonal parabionts, for example,
a blood chimera need not exist even when immunological tolerance between partners
is present (Hawk, Hraba 1955). Information about immunological tolerance in man
may be gained only from skin grafts. These have not been carried out, however, on
human twins in a sufficient number of cases to enable definite conclusions to be drawn
(Rogers, Allen 1955). Greater attention should be paid to this question, as it is
possible, that in human twins skin grafts might be utilised for the diagnosis of
zygosity.
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IK sonpocy Mexaxr~aMa RecTpy~cul~i~ roNZOTpaxcrl~IaxTaTOI~
L CpasxllTenvHOe rllcTOalorll~eclcoe 1lay~etlHe asTO-, roMO- I1 reTepoTpaxcn.riaxl~aTOti
YI. aYTHAFI
Ti I1l)JIOP1tiIfCHI1F1 IIHCTTITyT tICAII, 3ISCIIfpIIME'IITaZIbHF1H ~IIOJIO PNH kI P~~H(?T I1Ka, ~pBPR
Talc ~reneph yore loporuo II3IIec~rr~o, ;~ec?rpylcuusl ro~o~rpallcrl~IaHTa~ros Nac~ryuao.i.
ii pe3yalbTaie IIMMyH1ISaI~aI1 per~KnvlexloB Tpaxcualaxl~al~aMal (Colto~IOS 9923, 192/i,
Medawar 1943, 1945) >2 s caMOM n1llpohoM IIOHIIMaI1uI1 Ilpe~~cTaB3r3eT, Tar:Ii~ o6pa3oM,
O~jNII I13 TI11U)B 3aI1[I1'I'HbIX pCBKgIiII OpPaHN;iMa, - II 3TOM C-JIy~Iae I1MeIOli~NX 1[edI6H)
V;~aJIIITb ily}IZ(',pOj[Hble TKatllt. I~aI1 IIOI~a8aJi14 K.;[a('CI1~IeCISVie pa6OTGI MC9HIIKOBtl,
I[CpBOIIc9TIaJIbHOt[ 3a[T[I1TH0f[ peaISL~IICII, - MBXaNN391 IiUTOpOLI Ha IIbICIII6T% C"IyIIeHII~
pa3B1[TI1H NCIIIIOTHbI~ He~'C.TaHftO }'CJIO}ICHHCTCfl, - SIIIdIflCICA KTIeTO~IHhIf[ (~arO1[IiTO3,
3a~BaTLIRaiI1IC II O(r1e3BpC}IC11Iia11I1e ilyili('pO%~H61k 'ICn.
9IpK TOM TF11[C pealCgI1GI I1:~IMyH11TCTa, HOTOpblll OCVII[eC'CBJIfICI'CH I1pII IOMUTpaI1C-
llJIaHTaTa3~ Ile 6liL~o ;~OlCa3aH0 HaJIVI9t1O IjNpIC~'J7I1pyI0II~IIX I3 1CpOIiII aHTI1'CCJl II HL
~'JjaBaJIOGb OCR"II[CCPBNTb I7aCCIIBH}'IO IICpCr[aRy FIMIVIyHIITe'fa C GGIBOpOT[COII. ~~;lHBK~~
yT~a7IOCb yCTpaHIITb pea[CI[NIO I'p$HCIIJIilHTal[IIOHHOTO PIMMVHl4T0Ta IIyTCM 11MMVH0-
norl3~eclcoro c6~u,+rcllnx (PaIIIeIC 1953, 1954, Willingham, Breut, Medawar 1953,
1955 h CO3J~aTb IIaCC1IBHbIL1 LIMMyHn'CCT IIyTOM IICpeCaAICII JIIIM(~aTn9eCKOTO y3Jla
~M1CC}lISOII 1954. ~h('-I HC MeneO IIOj[pO6HOCTn MCXilIIn3Ma JjeCTpyligkill I'OMU'CpaHC-
IffiaHTBTOB J~O HBCTOHIL[CPO BpeYIOHII HL' BhIHCHeHbI.
W pa6OTas Il0 MIIKpOCICO11M9ecKOMy I43~'~IeHnIO z(eCrpy~cgiln POMOTpaHC1IJIaNTdTO13
OllkicbIBaeTCH V~IaCTIIe B HCIi JIOKaJIbHOn pealCljlln, XapaKTCpn3y1O11[el[CH ICJiCTO9Ii0Ii
IIH(~IIJIbTpal[IACIi N HapyIIIOtILICM ICpOBOCHa6`COHPIH TpaHCnJIaHTBTa ~L.Oe~ 993,
Medawar 1945, 1953, Dempster 1.951, Darcy 1952, Conway c corp. 1952, 1953x,
99536, Scotthorne 1953x; 19536, Mollroe 1953, Willingham c corp. 1954, 1955,
Woodrul 1955). LITO xacaeTCR x~eTOgnoi-l ntic~n~bTpaunu, sx>IMaHiIC IiccalenosaTe~ei~
cocpeRoTa~nBaeTCx IIa sonpoce po~Il ~InNt~ou[~TOS >7 n~a3MaTllueclcllx x~eTOh, Ilpn-
cyTCTBne xoTOpi~x Ilpn paapynlexilll roMOTpancn~all~raTOa c~IinTae~rc>I xapakTepm~I:~.
Ouxizi,I I33 o~eHb sepoxTllbla o6~hxcxexNli nx po~I1 xB~ueTCA rllnol~eaa, =ITO nocpe,~-
cTBOM aTrlx K~eTOx, cneun~nuecxll srlAon3Mellexxbla IIO,( ueFlcTSalenl anTllrelw>i n3
IcneTOir Tpaxcn~atlTaTa, anTnTe~a npllBO~HTCx a conpnlcocxosexlle c nepeca;ueHxoi~
T[C8HbI0.
Medawar-y (9.948) xe yAa~ocb ~,oxaaaTh Ilann~Ina un'roTOl.cnveclcoro z~ei-icrrII11II
JIIIM(~OI[IITOB Ha hOMOS[OPN~IHbIO IC7IeTICII 3IJI1~CpMbi B TIiaHOBbIX ICVJ[bTypa\ 113 1'I:aHCn
ILMMyHLI3IIpOBBHHbIX 51SnBOTIIbIX. Medawar IiOHCTBTnp}'CT j[aTIee~ 9T0 II IInTCHCl1ftHOCTG
IIOCIIaJInTe7IbHOII peaKl);RPI, II I~JICTO~IHaR IIH(~[4JIbTpaI~YIFt 6lilnael' HCO~[nHBKOIIa V' pa3-
~~iHT{HbIX 'tICIIBOTHbIX. YIxTellcnnxaR KpyrJIOIiJIOTOiIHaA IIH(~IiJIbTpaI~IlFi, cO11pOB0}H~[a-
fOII[aH pa3pyluenne POAIOTpaHCIIJIaHTaTOB y KpO.InICOB, IIO 0T0 MHCHnfO, MOiiie'I' 6b[T6
cepo~orn=Ieclcoii oco6enxocThx~ sTOro sHna (Medawar 1953). I~IccJle,~osannsl roMO-
~rpaxcalJlal~TaTOS ~? noMOnlhlo Texxlllcn ~Ir~I~~~~3sloxill>I~ I.aMeP (:llgire 19/13)
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NOAa:]aJIII, 9T0 MbIIIINHBx I'OMOJIOI'N11Hax '1'KiIHb BhI13CNBaeT, eCJIN B xaMepy H0 MOryT
HpoxNxaTb xneTxH xosxxxa (Algire c corp. 1954, PrehH c corp. 1954). PTO ycnoBNe
co6Hlo~aeTCx Tax, xTO cTexlcll zlaMepbl o6paay eT (~N7IbTp c NopaMN ullpeAesexHbix
pa3MepOB, j[eJIaIOIIjHN B03MO1IiHbIM Jjx(~(~y3NOHHOe IINTBHNe HJIeTOK B KBMepaX
IS B TO ?ll'e BpeMx OTj[e7IHIOIIINII NX OT K7IeTOK N TIfaHeH X03HHHa. IIpN IIOCJIejIHNX
HCCJIeJjOBaHNHX I'OMOTpaHCIIJI8HT8TOB C HOMOIIjbIO 3TON TCXHNI{II ~WeaVOP C COTp.
1955), - xorAa peluancH BOIIpoc, noTOMy-JIN K7IeTKH B ~Ilc~r~yaNOxxoH I:aMepe
BbIx:IIBa]oT, xTO (~I1JIbTp IlpeucTaBHaeT co6oi~ 6apbep j[JIH aH?rNTen, NJIN }Ke noTOMy,
tITO (]Ix~IbTp lIpeIIHTCTByeT COIIpIIIiOCHOBCHNIO Me?KZIy xJIe1'KaMN KVJIbTypbI N KJICT-
KBMII X03Hxxa, - 3TN aBTOpbI IIpNHI:III I# BbIBO~Iy, iITO KNMMyHN3NpOBaHHble> KJIeTKN~
BbI:3bIBaIOHINe CMepTb KJIeTOK B jlH(~(~y3NOHHON xaMepe, II B TO 1ICe BpeMH HOTNC~alOIllNe
CaMN, - 3T0 7INM(~OIINTbI.
P, HacT'oHHIeH pa6are, sIB~IxIOIge~~csl HaHINht HepBbIM BI:~IaAoNI B Realo N:3yvexNx
MOXc`iHN3MOB pa3pyIII0HHH TOMOTpaHCNJIaHTaTOB, MbI ITpNCTyHNdIN K peHICHIIIO 3TOT0
BOHpOCa Ha OCHOBe CpaBHIITeJIbHOTO TNCT07IOTNLIeCIiOTO I1:3y~I0HNH aBTO-, TOMO-
x reTepoTpaHCHHaHTaTOB y xpbic, MbliueK II ublHnxT, a B oco6exxocTN xapaxTepa
K7IeTOi3HOII HH(~NJIbTpaH,NN IIpIi OTHaj[eHHH rOMO- N TCTepOTpaHC1I7IaHT8TOB.
blantepuan u .acertt~t7ra
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B HQCKOnbKNX Cep nxX. B I CepNli 30 I{pbICBM B B03paCTe 3 MQCxIIeB nepeCa}KNBanaCb HO>Ka 2-MCCftY-
HbIX Kp bIC. BO II CepNli 20 3-McCniIHbIM K{~}bIC&M nepeCa?KliBanaCb KO}E{a 18-jjxeBHbIX KpbICITHbIX
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J~eJIaJI1ICb nOBTOp Hble rOMOTp aHCxJIaHTaIjiTN C 3IHTep SanOM B fi HeJl;enb nocne nepso# onepal;Nx.
B I` Cepnn y 10 KpbICSIT B B03paCTe ~ HCJ~enb npON3BOJ{NnNCb KOM~I1HNpOBaHHble aBTO- N TOMO-
TpaxCxnaHTaIInN, B V CepNI4 - B3aNMHble rOMOTpaHCNnaHTa.IINN y 20 J~ByXMQCxTiHbIX KpbIC,
B VI CepNN - B3aNMHbie rOMOTpaHCnnaHTaiINN y 14 J~ByXHeJ~enbxbTX I.~bInnxT. B VII CepNN npo-
NasoAnnxcb reTepoTpaxcnnaxTauNN, npNYeM peunniiexTaMN 3RAcb fibrno 20 Kpbic, a AoxopaMU -
5 TpP,XMeCx9HbIX MbInIe~,
IIpN BCOX NepeCaJ{KaX MbInIaM N KpbICaM np NM0H xnliCb OJ~HN ]i Te }Ke npneMbl, 3a ~exb J;0 OIIe-
paijNN IDepCTb Ha CxNHKe y J;OHOp OB N y pf.l);NnNeHTOB OCTOp O}KHO Cfp NBaJIaCb. IIepeTl nCpeCajli(0 ~1
ONCpaI[NOHHOe none Ae3NH(~NI);NFOBanOCb PNI~IeHOM N CNNpTOM A nOKpbIBanOCb TOHKNM CJI00M
KOJInO{"lnn C npNMECbIO KBCTOpOBOI'O Mama N KaM(~)Opbi (Cannon, Longmlre 1952), I-CorAa ox 3a-
CbIXaJI, MbI BbIpe3ann Anx nepecaAxN 70HKNMli, OCTpbIMN HO}KHNIIaMTI 90TbIpCXyrOnbHll4 Kli
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MbI Ha paHbI Ha neBOI~] CTOpOHe CNNHKII npiiKnaJ~WBanN aBTOTpaHCnnaHTaTbI, a xa npaBO# CTOpOHe -
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IiX I{0 ~Hy paHbI CTepNnbHbIM TBMNOHOM, a nOTOM nOKpbIBanN TOHKNM CJIOeM KOnnOJllix, KOrAa
OH 3aC blXan, OxepallNOHHOe nOnC nOKp blBanOCb npONNTaHHO~i Ba3enNHOM Mapnel"l, KOTOpan l~)NKCIi-
pOBanaCb nE~IKONnaCTbipeM ii HBCKOdTbKNN[ Oi)OpOTBMN PNNCOBO~I nOBn3K11 BITipIIHOI7L B 2-3,5 cM,
CMOTpiI x0 pa3MepaM }i{nBOTH0r0. IIpN KOM~NHNpOBaHHbIX aBTO- H rOMOTpaHCnJIaHT8T8X MbI nepe-
CaH{NBanN nOnOCKN KOx{N B O,4 1 CM, nOMenlax NJIN aBTOTpaHCxnaHTaT Me}KZ[y 2 rOMOTpaHCnnaH-
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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CTOHigaH HO hOJIbIIICIi i1aCTH H3 1'paHyJI0I1,HTOR, COXpaHHCTCH; O HaJIH~IIIH BaCK~'JIH-
pH3aI>;HH TpaHCHJIflHTaTa Ha 4-5-bIH j[eHb CBH,T[CTCJIbCTB}'IOT pa3pC3bI COC~'~OB Ha
IIpeIlapaTaX. MbI HC Ha6JII0j[aJIIt 3~[eCb MH'I'O3a H IiJICTIlaX 31lLIj[epMbi. ~~CreHCpa-
THBHble H3MCHCHHH 3IIHAepMbI HBCTyHa7IH B HaIDHX OIIbITBX OiICHb paHO, HanJ1I0-
jjaJIHCb yHCC Ha 4-rJ-bIYI J>;CAb H IipOHBJIHJIHCb, -Tax iliC, Iia7: H ]IpII rOMOTpaHCIiJ18H-
'faTBX, - y'TpaTOIi t)a3O(~HJIbHOCTIi I]HTOHJIa3MbI I:JIC7'ICaMH 311 GIj[CpMLI lI IiX RdIC`'OJIII-
3aH;HCH. C:pe~H ICJTCTOK 3HHZ[CpMbI Mb1 }'iliC Ha J-F-OIT j[CHb BCTi7CiI8JIH JICIiKOIjiiThl.
B HH(~HJIbTpaTe BO3paCTaCT KOJI1I9eCTB0 JIHM(~iOI);HTOB, IfJICTOIi HepexOj);HOl'O THlla
H H7Ta3M8THYCCICHx K7IeTOK. ~ia 6-7-OI3 ji,eHb OvIH1IpHbIC I'eMOppal'llH IIOIipbIBBNI'I'
scio HJrolua~b reTepoTpaxcHJlaHTaTa (pllc. 9). MHOrNe H3 HH(~IT7ibTpHpyIOlflHx xneT~uc
pacnaAax~TCH B Me~xyio sepHHCTOCTb. ~nH~epMa H OCTaJIblible TxaHII reTepoTpaxc-
HJ1aHTaTa HexpoTHaHpyioTCx. B J1ox,e TIOA reTepoTpaHCHaIaIITaTOM npoTeicaeT Tal:a;l
~ICe peaxuHSi pblxJloil coenHHHTeJlbxoii TxaHH, xai:aH 6bIJIa oHHCana ~' roMOTpanc-
HJI8HT8Ta. IIa g-1~-bIi3 J>;CHb HCI{pOTH3HpOB8HHbIII reTepOTpaHCHJIaHTBT BbITaJII:11-
BaeTCH B pC3yJIbTaTC 6~'pHOH pCaKIjHH TKaHH pCIjHHHCHTa, Ha CPO MCCTO CO jIH21
~aHbI Haj(BHI'aCTCH rpaHyJIHIZIIOHHBH TKaHb, (' xpaCB paHbI BOCCT8H8BJIHBaCTI'71
3HHJjCpMa pCIjHH1ICHTa, Haj[BIiTaIOIT~aACH IIOZj TH8Hb10 6bIBHIeI'O TCTCpOTpaHCHJiali-
TaTa (pNC. 10). Ha 9-10-bIi~ nexb cTpyn oTnaAaeT H Ha er0 MecTe ocTaeTCH p~~6eu.
IIOKpbITbIH BbTCOIC1IM, 3HatIHTCJibHO haRO(~HJibHbTM 3HHTe'iHCM.
~llCl#~~CCil.ft
1~bI OHHC3TIH XapaK'L'Cp IICpBl19HOT0 IIpH5ICIIBJICH4IH aB'fU-, CUMO- ll rCTCpOTpalll'-
1IJIaHTBTOB II MOp(~OJIO1'HiICCKVIO KapTHHy J[eCTp~'ICIjHH rONlO- H 1'C'ICpOTpaHCIIJTaHTa1'OB.
y rOMOTpaHCHJT8HT8TOB MbI IIpii HO~I,pO~HbIX MHKpUCKOILH9CCICHX HCCJIC~OBaHHHX
OTMC9a7IH BHa9aJi,e VMCpeHHyIO Kp~'rJIOK;ICTU9H~'IO HH(~HJibTpal[HIO, HpC;jCTaBJiCHHti'IO,
I'JIaBAbIM Ohpa3OM, JIHM(~IOI~HTaMH H (tTBHOBHITj}'IOCH B TCiiCHIIe j[a7ibIICIiHIO1'O pa3BHTIIH
BCC ~OJIee HbIp83H'1'CJIbHOH. ~~ MbIHICH, Kpb1C H Il,bIIIJIHT OHa OObINHO conpoBO~i~,~ae'rrsi
pa3p~'IIICHHCM rUMOTpaHCIIJI8HT8Ta. ~);[IIORpe~MCHHO C ~'CHJTCHNCM IipVrJIOICJICTOiIHO}i
HH(~HJIbTpaI[HH Mbl Ha~JiIOJ(aJIH H rOMUTpaHCHJI8H9'aTaX IiIIICpCMHiICCKNC H Jl,a}IC('
3aKVHOpCHHbIC COCA"JI,bI C MCJIKNMH T1JIH OFIIIHpHbI3i17 TO4O9HbiM11 l: p~)BOH3JIHHHHHMH,
NIOp(~O7IO1'N~iCCKH XapaKTCpH3yI0IIl,HC HpeKpail);eHHe ICpOBOOhpalllCHHH R rOMOTpaHC-
]IJI8HT8TC. 1~bI CiiIITaCM BaiICHbIM HOARJTCHHC H 9IlHt[CpMC ;jCI'CHCpaTHBHbIX lti1MCHCIiiI11
H CBH3H C ISp~'rJIOKJICTO~IAOIi IIH(~1HJ1bTpaI~HCIi H paCHaf( CBMNX I:JIC'fOH HH(~INJibTpaTa,
fla~7iI0~[aIOIi),HPICH B COCC~(CTBe C. ;(CPCHepHp}~IOTgHMIi ICJTCTICaM6T rOMOTpaFiCHJIaHTBTa.
UTCIOj[a MO1IfH0 CjjCTIaTb BbiBOy~ O CIIeIjH(~TI9CCI{OH pOJIN JIl1M(~IOL[NTOB B CM6I('JIC
rHHOTC3bI O HO~[BO3C aHTHTCJI 3TH1~TH IiJICTICBMH. 110 HaIDCM~' MHCHIIH), IIOCAOJiblfV'
BOO~)il1;e jl,Ollti'CTHMO TIpC~HOJIaraTb HaJIHiIHO CHCIjH(~H9eCdiOH pOJITi HH(~HJIbTpHpV'-
IOIi[I1X TiJIeTOIi, ('7IC;1,~'CT rOBOpHTb O IfJICTO9AOH HH(~HJihTpaljHH IIl t{)tO, IIMCH B BH~\
KpOMC JIHM(~)Ol[HTOB, HBHCOJICC MHOPO9HCJIeHHbIX B BTHX CJiyiiaHX, T8K}KC KJICTI:B
IICpCXOJjHOTO TH1Ia TI ]TJIa3MaTHtICC3SHC KJIeTIfH, HpeJl,(''IaB7IHI0ITjHe, BCpOHTHO, (~yHR-
I(HOHa7IbHbIC COC'IOHHIiH OJ[HOI'O H TOl'O )1~C THIIa ICJICTOI{. ~aP('~' ~19J2~ HCCJIC~OBaJl
KpyrJIOKJTCTO9H~'IO HH(~HJIbTpaIjHIO B rOMOTpaHCHJI8HT8TaX }' ]ipOJiHKOB H Ha3BaJl
IICpCXOZ[HbIC TI[IIbI KJICTOK ) IIJIaBMaTITYCCKHMII IHJICTICaMH, TIpH9C:~l
OOJIbTHyIO uaCTb HJIeTOK KpyrJIOIiJICTO9HOI'O HA(~HJTbTpaTa C MOp(~OJiOPHiICCI{OH TO~II(11
:IpeHHH MOiIiHO ~bIJIO HpOH3BOAHTb OT JIHM(~OI[HTOB, a MCHbIII~'IO 9aCPb -- OT peTHK}'-
:iHpHb1X KJICTOIi. NTax', MOiII'HO CJZCJIaTb BbIBOJj, LITO II7Ia3Ma1'iILICCKH@ IiJICTKH B rOMI)-
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
TpaxcnJraHTaTax 6bIB8IOT npeHMyH~ecTBeHHO JITIM~ouHTapxoro IIpollcso;r,~~eaHSI.
~eRTeJibHOCTb rpaxyJroui3TapHb1X JIeiIKOuHTOB, KoTOpble - 110 xalnnM Ha6J1IO1[e-
HHBM - HpnxHMaIOT ykacTr~e B peaKuHn TOJIbKO TIOaRHee, HanpaBJreHa aAecb, rnaBHb1M
06pa30M, Ha OT~eJIOHHe HOKpOTH~IeCKOn, pa3pyIHCHHOFI npGj[IIIeCTBOBaBIDHMH THIIBMId
KJIeTOK TKBHn. IIOCMOTpH Ha TO, LITO B HpenapaTaX Darcy ~19J2~ B rOMOTpaHCHe'Ialt-
TaTBX y KpOJIHKOB BCeI'Jja Ha~JIIOJjaJIaCb JIBHKOuILTapnaH HH(~IIJIbTpal(HH, 3TOT aBTOp
BbICTyIIaeT IIpOTTIB MHOHHH O CneuH(~ITileCKOH pOJIH JIHM(~OuHTOR, TO~IHee, - HX
peIIIaIOIi[eH pOJIH B HpOueCCe ~eCTpyKUHn rOMOTpaHCIIJIaHTBTOB. IIO er0 MHeHH10,
JIHDI(~OuHTbI CBOHMH 3H3HMdMII MOryT CHOCOGCTBOBaTb pa3pVI1IEHHIO IIpOTOHHOB TpaHC-
IITIaHTBTa. I~ICXOJ~FI H3 pa60T Z~rOWell-a (1952) O 9}~BGTBHTeJIbHOCTLI JIHM(~OuHTOB
H HeJ~OCTBTIty ItHCJIOpOJ~a, Darcy CLIIITaeT HaI160JIee HpOCTbIM OE'bFICHCHIteM IlpO-
HCXO1KAeHLIH pa3pyHI8HHbIX JIHM(~OUnTOB R rOMOTpaHCnJIaHTdTe KIICJIOpOJjHOe rOJIO-
j(aHlie TKaHn B pe3yJIbTBTe HpeKpalueHnH B HeII KpOBOO~paH[eHHH. LITO ItaCaCTCH
HJIa3M3THzIeCKnX KJI@TOK, Darcy OTpHuaeT HX 3HaiICHHO j~71H j[eCTpyKI~HH rOMO-
TpaHCHJI8HT8TOB en[e pell[HTeJIbHee, iIOM B CJIy~Iae JIHM(~OUHTOB, XOTH H HC rOBOpnT
IIpHMO, LITO IIJIa3M8TnLIeCICIIe I{JIOTKH HC MOry'T BbIjjeJIHTb R rOMOTpaHCITJIaHTBT
aHTHTCJIa: RPe30p61[HOHHaA T00pnFI (~)VHKI~HH IIJIa8M8THiICCKHX KJIeTOK JIy9IDe
OC'bHCHHOT nOJIy9eHHble pe3yJIbTBTbI, TieM TeOpHII BbiJl,eJfeHHH aHTIITCJI>, yTBep}1tJ],aeT
Darcy, ccblJiaacb xa pa6oTbl Dubois-Ferier (1951), hoTOpbl~i Ilou~epKHSaeT, vTo
rJlasxoH (~yHKI(IIeI3 nJlasMaTn~IecltllX KJIe'rort IIBJIHe'rcx peaop6uHH II Heii'rpaJlHaauHH
=Iy}Kepo~Hblx npoTennoB. OAHaxo Kidd (1950) H Ellis c c-oTp. (1952) uoxaaanH
HaJIIhIIiC uHTOTOKCHileCKOTO JjenCTBHfI, HHItyUIIpyH 3JIOKa~IeCTBEHHbie IiJICTKH C ItJIOT-
KBMDI JIIIM(~aTHiIOCKOI'O y8Jia MbIIIIH, upeuBapizTeJrbHO HMMyHH3HpOR8AHOlI TOIi ?KC
OIIyXOJIhIO. ~HM(~Oun1'hI HenMMyHn3npOBaHHbIX MbIHIen He O~JIaJjaJIH ~1'HM T~e1ICTBHCM.
HanpoT~B, Medawar (1948) Re HaxoRHJ1 unTOTOKCH~ecKnx aHTHTen npoTHS roMOno-
rH9Hb)X 1tJIeTOK 3n HJjel)MbI B JIHM(~aTnKeCKHX TKaHHX nMMyHn3npOB8HHbIX KpOJIHI{OA.
Bellingham H Sparrow (1954) HaIUJIn, =ITO TnnHVIIaR MecTHaH pealtunll, npoTelta-
IoluaH s uepMe 1)pH paapymeHHH roMOTpancnJraHTaTa, ocyntecTBJIHeTCx Taxxte
B Jjli(~(~epeHijHpyIOIuCnCH rpaHyJIHuHOHHOIi TKBHH peL[IIIIHOHTa, CCdIII ',[JIH nepCCaj[Kn
IIpnMeH}IOTCH 311H;[epMaJlbHbIH rOMOTpaHCnJI8HT8T, I[pH9CM LI 3j[eCb XapaKTCpHbI
KpVrJIOHJIOTOTIHBR pCBKunH H 3aC'IOH KpOBn B COCyZ[aX, C nOBCpXHOCTHbIMII 9p03HIIMH
Its aRuoTeJIHR. Mitchison-y (1954) yRaJracb Ilepe,ja~a MbIIUaM naccHSxoro nMMyan-
TeTa K J1HM~xx?apxoMe nyTeM nepecaAKII JiHM~aTHUecKHx yaJioR, no ne yp,aBaaracb
uepe;~atla c HoMOn~blo cblBOpoTKn HJIH nepeTOHeaJir,HOro ~Itccy,CaTa. Burnet (1949)
Ho~zaraeT, yTO MexaHnsM uecTpyltuHH roMO'rpaHCnJraHTaTOS no~,o6eH csepx~yBCTSn-
TOJIbHOCTH K TyFepKyJINHV? TIO er0 CJIOBBM, llpn COIIpHKOCHORCnHIi TpaHCIIJIaHTBTa
C KJIBTKaMH X03HHHa M05KeT npOI130HTn MCCTIIOC BbIjjeJICHHC 3TNX (~)apMaKOJIOTHiIOCKH
aKTHBHbIX B01ueCTB, BbI3bIBaIOIuHX H0Kp03 IIpH BIIOJIHe pa3BCpN}'T6IX Ty~CpKyJIH-
HOBbIX peaKl[ISHX. Blllingham (1954) R CB00M IICCJICjjORBHITn, IIOCBAIuCHHOM y'jOKa3a-
TOJIbCTBy HaJIn9NH unTOJ101'HiICCKOH aICTHBHOCTH B CbIBOpOTKe n pa3JIII9HbIX IIpena-
paTflX H3 TKaHen nMMyHHbIX }itnBOTHbIX, IIpHCOCj[HHHOTCH Ii0 B3rJIR~V, 9T0, KpOMe
areHTa xapaK?repa uHpxyJlHpyIOIuHx axTHTeJI, :Iuecb MoryT ue~TCTBOSaTb Ha KJreTKH
K BeIueCTBa B CBH3anHOM COCTOHHnH, - ~blTb MO>lieT, Cahn aHTnTCJia, KOHTaKT
ICOTOpbIX C aHTHI'CHOM Bb13bIBaeT Rblj[eJI6'HHe HCCIIeI~N(~H9eCISHX aISTNBHbIX c~apMa-
KOJIOrn9eCitliX BCH[CCTB, RBJIHIOLuHXCH IIpH9HHOn HeKp03a rOMOTpaHCIIJIaI1T8Ta.
IIO MHeHflIO ~ICI1Wal(I-a (1953) B03MO1fiH0 TBKiKe, 9T0 J1,JIH j[eCTpVKI[Itli rOMOTpaHC-
HdIBHTflTa neOCXOjjHMO HCCKOJIbKO TNHOB aHTHTeJI, KOTOpble MOryT j~CI1CTBOBaTb paa-
JIH9H0: OJ~BH IIOCpeJ[CTBOM BOCHaJIHTeJIbHOH peaICuHn IiJIH BBCKyJIFIpn3al~nH, upyrKe~-
r[enCTByH npHMO Ha ItJICTItn TpaACnJIaHTaTa. 11T0 KaCaeTCH pOJIH BBCKVJIFIpII3auHH,
Onb[TbI Medawar-a (1948) C BbI?ItHBaHHOM IIOBflCKyJIHpn3HpOB8HHbIX I'OMOTpaHCnJIaH-
TaTOB B nepeAHeH ItaMepe I'JIa3a CneuH(~niIOCItYi nMMyHH3npOR8HHbIX KpOJIffiCOR
rOBOPHT OOOJIbIIIOM 3HaYeHHII 3TOI'O (~a1tTOpa. ~: j(pyrOYl CTOpOHbI Merw)II K Illll
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
(1954) noxasanN, *1TO xesacltynflpNaNposaxxbie roMO'rpaxcnJlaxTaTbl B NoRlto}KxoH
TKaHN paspylHaloTCfl, eCnN OHN 6bInN Hepecax{exbI CneIjN(~N9eCItN NMMyHN3Np0-
BBHHOMy peIjNnNOHTy. B CBfl3N C BOHpOCOM MOXaHN3Ma JjeCTpyKIjNN rOMOTpaHCHJIaH-
'raTOB OCOCeHHO NHTepeCHbI NCCnej[OBBHNx rOMOTpaHCIInaHTaTOB B j[N(~(~y3NOHHbIX
KaMepax. Algire (1954) N Prehn (1954) npxsoRHT, ~ITO Bo3MOHtxo HoRRepxtNBaTb
}KN:3xb HOpManbxbIX N 3nOKa~IeCTBOHbIX TOMOJIOPN~IHbIX KneTOK C nOMOnjbIO aJj3KB8T-
HOI'O IINTBHNfl B ~pIOIIIHON nOJIOCTN MbINIeII, eCnN KBMepbI C nOpNCTON nneHKON
OTJjeJIHIOT NX OT KneTOK N TK8HeI3 XO3ISNHa. IibIJIO yCTBHOBJIOHO, LITO B 3TNX yCJIOBNHX
rOMOJIOrNYHble KJIeTKH MOPyT BbIHtNBaTb Ii B NMMyHN3NpOBaHHOM XO3HNHe, HO
HNKOrJ];a H0 CNOCOCbI CBMN BbI3BaTb NMMyHNTOT (Prehn 1954). LITO Kacae'rcfl axa*IeHNH
JINMC~oI[NTapxoil peaxljNN Rnx RecTpyKijNN roMO'rpaxcnnaxTaTOB, Aaxxble Weaver-a
(1955) CBNJjeTenbCTByIOT B nOnb3y 3TOT0 IIpeJj1IOJI0}I{eHlifl, K ileMy MO}KeM lIpNCOeJjN-
HIiTbCIi N MbI Ha OCHOBe IIOJIyLIeHHbIX HBMN pe3ynbTaTOB. B pa6OTe Weaver-a CHOBa
Fbino OTMei3eH0, LITO I'OMOTpaHCIInaHTBTbI (Kpy}KO9KII 3IINJjepMbl) BbI}KNBaIOT B J~N~ic~y-
3NOHHbIX ICaMepaX C HeHpOHNI[aeMbIMN jjJIfl KneTOK CTOHKBMN Rax{e B TeJIe IIpeRBapN-
'fenbHO YIMMyHn3NpOBaHHbIX 1'OMOJIOPNIIHbIX XO3fleB. ~j[HaKO rOMOTpaHCIInaHTaTbI
He BbI}I{NBBIOT B TOTepOI'OnN9HbIX XO3fleB8X, B OCO~eHHOCTN eCJIIi OHII fbinli NMMyHN-
:3NpOBaHbI, LITO NCCneAOBBTenN HpNBORxT B JjOKa3aTenbCTBO TOTO, LITO KdMepbI npo-
xNrjaeMbl ~jnfl axTNTeJI. IIanpoTNB, roMOTpaxcxnaHTaTbI B npoxliljaeMblx ~[nfl xJleTOit
1taMepax IIOTN~OaIOT B rOMOJIOTNIIHbIX XO3fleBaX ~Iepea 2 HeJjenli (a B 1IMMVHN3Np0-
BaHxbIX - paHbnIe 2 HeJjenb), npN flBneHNHX nNM(~)OIjNTapHOH NHBa3NN. Ecnli
B I{JIOTKOHenpOHNljaeMbIX Z[Ii(~(~y3NOHHbIX KaMepaX KynbTNBNpOBanNCb 113OJIOTIiLIHble
fl0 OTHOID0HNI0 K XO3FiNHy KJICTKN 31INj[epMbI (aBTOpbI IfOnb3OB8JniCb ~JIN3KOpOZj-
CTBOHHbIMN IiIT8MM8MN) COBM6CTH0 C KneTItaMN Cene3eHKN N3 MbIHIN, llpei[BapNTenbHO
6iMMyHN3NpOBaHHON HpOTI1B KneTOK TKaHEBOn ItynbTypbI, TO KneTItN 3nNjjepMbl
B KBMepe IIOl'N~OanN B TeLIeHNe HeJjenN. IIO MHOHNIO aBTOpOB, eCJIN nNM(~OIjNTbi npN-
xOJjflT B COHpNKOCHOBOHNe C KJIeTKaMN, IIpOTNB I{OTOpbIX OHN ~ObIJIN NMMyHN3Np0-
BaxHbl, To ocxo6o}KAaloTCfl BefuecTBa, N o6a TNna Kne?rox norN6aloT.
LITO KacaeTCfl HapymexNfl Kposoo6paN[exN>I B roMOTpaxcrinaxTaTe, KoTOpoe, no
'Taylor-y (1955), cneuyeT c~fIlTaTb xauanbHblM MoMexTOM ~ecTpyl{i[Nii roMOTpaxc-
IInaHTBTa, TO HOny~IeHHble HaMN pe3ynbTaTbI He xOJ[TBepllij[aIOT II pC;[IIOJIO}KeHNfl,
9T0 HapyIneHNe KpOBOCHaC}1{CHNfl MOPJIO 6bI Cny}I{I1Tb HelIOCpeT,[CTBOHHOIi HOCIIeIjN(~N-
9eCKON npnHnHOII pa3pyIIIeHI1H rOMOTpaHCnnaHTBTa. ~3 HaIIiCI'O OilfiCalllifl MOH{xO
BNj[eTb, ilTO JjereHepaTNBHble I1:3MexeHNfl B 3nN~epMe HaLINHaA)TCfl B CBfl3Ii C nHM(~O-
I[NTapHOII nx(~NnbTpaI[NeN nnN paHbine, Nnx ?OJjHOBpeMOHHO C IIOHBJICH1iCM B TpaHC-
nnaHTaTe TOilei3xblX KpOBONi3nNHHNN N O~Iexb BbIpa3NTenbHO npOHBnflH)1'Cfl Ha Cne-
lrylou[Iiii ReHb Hoene xapymexNfl IjNpICynfll[NN. Scotthorne (1953) Ha6nlop~an i[erexe-
paljNlo 3nN~jepMbl ilepea 24 naca nocne xapylnexNfl I{posoo6pax[exNx N cxpalleunxso
paCCy}ICJjaeT, 9T0 H0T 1IpNtINHbI, nOLIeMy bbl rOMOTpaHCllnaHTaT N F83 1[NpKVJIflI[NIi
He MOT B TeTieHne N3B0CTHOTO BpeMOHn IIOnyT3aTb IiNTaHIiO NyTOM RN(~ic~y3NN IIOJjOhHO
'folly, xax Ro BacxynflpxaauNN (IiepBble 3 Axfl nocne nepecauKn). IIpN csoxx rxc'ro--
xNMNUecKNx NccneRosaHNflx' Scotthorne (1953) xaiuen, nTO_ B AerexepnpyioluNx
1tneTKax 3HNAepMbi Nc~eaaeT pN6oxyKneNxosafl KNCnoTa, xo Bce elue IlpNCyTCTByeT
l'JIHKOTCFI .
MHOHNe ~.OI1Way-II (1952), ilTO COTb COCyJjOB rOMOTpaxCnnaHTaTa HejjOCTBTOiIHa,
MOH\HO, NCXOy~fl N:3 HaOJIIOj[eHNN MHOPOiiNCneHHblx pa3pe3OB COCyJjOB B npenapaTax,
TaKme oTBeprxyTb. Scotthorne (1953) NccneRosan BacxynflpxaauNlo aBTO- N roMO-
'fpaHCnnaHTaTOB MBKpOCI{OnNTIeCKN, 1[pN M@CTHOM HaHOJIH0Hn1I COCyZ[OB CpOM(~eHO-
JiOBbIM CNHNM, N MnKpOCKOHNLIeCKN, Ha IIpelIapaTBX N3 }KNBOTHbIX, ItpoBflxoe pycJIO
I{OTOpbIX HanOJIHflnOCb paC1'BOpOM TyIIIN, li He HaXOJjlin pa3HNIjbI B 6bICTpOTe N paa-
MCpaX BaCKynflpN3aljNx Me)I{zjy aBTO- Ii rOMOTpaHCnnaHTaTaMN y ItpOnNKOB. I~ICCJIejjO-
BflHNII BBCIt}'nflpn3aljxn rOMOTpaHCllnaHTaTOB lIl V1V0 B npO3paiIHbIX ItaMepaX
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
((:on~i~a}~ c corp. 1951, 1952, 1953a, 19536) nyahxo npnHnMaTb c ocTOpo,~;rlocThx>,
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
caRx~i, 6bicTpo xacTynaioiur3e uerexepaTHSxbie xaMexex~ix anKAepMbt x B~1Ta~ixx-
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nHexTa.
(Ta6n. XXXIII, XXXIV, XXXV, XXXVI)
P a xr e x, bf.: IIapa6noa nTni; so speMx ani6pxoxanaxoro paasxTnx. LIcn. Bnonornx 2 : 29,
?1953.
P a ni e K, M.: IIpotisstexxrt BereTaTnsxoro c6nnacexnsr s aAanTauHii sbicmnx ~xxsoTxbix xa vyx:c-
poAxi~ie axTnrexii. LIc.i. Snonornn 3:344, 1954.
JI o n a m o B, B. I'., C T p o e s a, O. I'.: PaasnTne nMniyxonorn=iecxxx peaKilnlt n npo6.neMa
xecosMecTxniocTn Txaxeil npn nepeca~Kax. Ycn, corp. 6xon. 30:234, 1950.
M e Y H ii K 0 B, ~, II,: BOnpOCbI nMMyHATCTa. MocKBa 1951.
l: o if o .n o s, H. B.: HepecaAKa opraxoB s cBxax c peaxuneii iininiyxxTeTa. Iiaaax. Meu.:Kypx.
19:3, 1923.
C o x o ~ o B, H. B.: HepecauKa opraxos c Tovx~i apexnx xl~Myxo~torxri. Tpyn~>i XVI c, pycc.
xnp. 196, 1924.
X y z x a x, H.: 3axcxs~iexxe axenepxMexTanaxbis pax. 2. Tpaxec~opMagHx K.neTOx npx aaxcns-
sexxx paxbi. LIcn. BnOJlOrnx 3:168, 1954.
A 1 g i r e, G. H.: An Adaptation of the Transparent Chamber Technique to the Dlice. J. Nat.
Cancer Inst. 4 : 1, 1943.
A 1 g i r e, G. H.: Tissue Transplantation Conference. J. Nat. Cancer Inst. 14:687, 1953.
A 1 g i r e, G. H., Weaver, J. M., P r e h n, R. T.: Growth of Cells in vivo in Diffusion
Chambers. I. Survival of Homografts in Imunised Mice. J. Nat. Cancer Inst. 15:493, 1954.
B i 1 1 i n g h a m, R. E., Brent, L., Medawar, P. B.: Actively Acquired Tolerance
of Foreign Cells. Nature 172:603, 1953.
B i 1 1 i n g h a m, R. E., Sparrow, E. M.: Studies in the Nature of Immunity to Homolog-
ous Grafted Skin, with Special Reference to the Use of Pure Epidermal Graft. Nat, J. Exp.
Biol. 31 : 16, 1954.
B i 1 1 i n g h a m, R. E., Sparrow, E. M.: The Effect of Priorintravenous Injection of
Dissociated Epidermal Cells and Blood on the Survival of Skin Homografts in Rabbits.
J. Embr. Exp. Morph. 3 : 265, 1955.
Burnet, F. M., Fenner, F.: The Production of Antibodies, Melbourne 1949.
Cannon, J., L o n g m i r e, W.: Studies of Successfull Skin Homografts in the Chicken.
Ann. Surg. 135:60, 1952,
Conway, H., Jos 1 i n, D., Stark, R.: Observation on the Development of Circulation
in Skin Grafts. I. Technique of Adaptation of the Transparent Chamber Technique to Study
of the Circulation in Skin Graft. Plastic Rec. Surg. 8 : 194, 1951.
Conway, H., Jos 1 i n, D., Stark, R.: Observation of Circulation on Skin Grafts.
III. Morphologic Changes Observed in Homologous Skin Grafts. Plastic Rec. Surg. 9 : 557,
?1952.
Conway, H., Stark, R., Jos 1 i n, D.: Observation on the Development of Circulation
in Skin Grafts. Plastic Rec. Surg. 11 : 7Fi, 1953a.
Conway, H., Stark, R., Jos 1 i n, D.: Observation on the Development of Circulation
on Skin Grafts. VI. Effect of Hyaluronic Acid and Homologous Skin Filtrate on Homologous
Skin Grafts. Plastic Rec. Surg. 12:1, 1953b.
Darcy, D. A.: A Study of the Plasma Cell and Lymphocyte Reaction in Rabbit Tissue Homo-
grafts. Phil. Trans. Royal. Soc., London 236:463, 1952.
Dempster, W. J.: Problems Involved in the Homotransplantation of Tissues, with Par-
ticular Reference to Skin. Brit. Med. J. 1041, 1951.
Dubois - F e r r i e r e, H.: Actualites hematologiques 1:43, 1951. (Cit. Darcy.)
E i c h w a 1 d, E. J.: Acquired Immunity to the Graft. J. Nat. Cancer Inst. 14:705, 1953.
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Lymph Nodes and Spleen from Immune Hosts. Cancer Research 12:259, 1952.
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77 :229, 1943.
H as a k, M.: Parabiosa ptaku v embryonalnim vyvoji, t~s. biologie 2:25, 1953.
H as a k, b1.: Projevy vegetativniho sbliiovani v adaptaci vyss"iho zivoLicha na cizorode anti-
geny, Cs, biologie 3:327, 1954.
C h u t n a, J.: Hojeni experimentalnich ran. II. Transformace bunk pi?i hojeni ran. ~s. bio-
logie 3:158, 1954.
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Kidd, J. G., 'p o 0 1 a n, H. W.: The Association of Lymphocyte s with Cancer Cells Under
going Distinctive Necrobiosis in Resistant and Immune Hosts. Am. J. Path. 26:672, 1950?
Loeb, L.: Transpplantation and Individuality. Physiol. Rev. 10:547, 1930.
Medawar, P, B.: Notes on the Problem of Skin Homografts. Bull. War. Med. 4 : 1, 19/i3.
Medawar, P. B.: A Second Study of the Behaviour and Fate of Skin Homografts in Rabbits.
J. Anat. London 79:157, 1945.
Medawar, P. B.: Immunity to Homologous Drafted Skin. III. The Fate of Skin Iomografts
Transplanted to the Brain, to Subcutaneous 'tissue and to the Anterior C:hambc+r of the Eye.
Brit. J. F.xp. Fath, 29:58, 1948a.
Medawar, P. B.: Tests by Tissue Culture Mothods on the. Nature of Immunity to Trans-
planted Skin. Quart. J. Mier. Sci. 89:239, 1948b.
Medawar, P. B.: Tissue Transplantation Conference. J. Nat. Cancer Inst. 14:717, 1953.
M e r w i n, R. M., H i 1 1, E. L.: The Role of Vascularisation inthe Survival of Subcutaneous
Homografts in Mice. Cancer Res. 12:282, 1952.
M e r w i n, R. M., H i 1 1, 1 L.: P'atc of Vascularised and Non Vasculariscd Subcutaneous
Homografts in Mice. J. Nat. Cancer Inst. 14:819, 1954.
1VI i t c h i s o n, N. I.: Passive Transfer of Transplantation Immunity. Proc. Royal Soc.,
set. B 142:72, 1954.
Monroe, L. W., A n d e r s s o n, I., Hass, I.: A Study of the Problem of Ilomogafting
by Means of Parabiosis in Rabbits. Plast. Rec. Surg. 1i : 15, 1953.
P r e h n, R. T., Weaver, J. M., A 1 g i r e, G. H.: Tho Diffusion Chamber Technique
Applied to a Study of the Nature of Homograft Resistance. J. Nat. Cancer Inst. 15:509,
1954.
S c o t t h o r n e, R. J., McGregor, V. A.: 'Phe. Vascularisation of Autografts and Homo-
grafts of Rabbit Skin. J. Anat. 4 : 379, 1953x.
S c o t t h o r n e, R. J.: Histochemical Studies of Autografts and Homografts of Human Skin.
J. Anat. 87 :22, 9.953b.
'I' a y 1 o r, C. V., L e h r f c 1 d, J.: Definition of Survival 'Pissuc of Homografts. A~. Y. Acad.
Sci. 59 :227, 1955.
T r o w e 1, C. A.: The Culture of Lvmph. Nodt~s in vitro. I~.xp. Cell. Res. 3 : 79, 1952.
Weaver, J. W., A I g i r e, G. H., P r e h n, R. S.: 'the Growth of Cell in vivo in
Diffusion Chambers. III. The Role of Cell in the Destruction of Homografts in Mice. J. Nat_
Cancer Inst. 15:1737, 1955,
W o o d r u f, M. E., Simpson, L. O.: Induction of Tolerance to Skin Homografts in Rats
by Injection of Cells from the Prospective Donor after Birth. Brit. J. Exp. Path. 36: 494,
1955.
On Questions of the Mechanism of Destruction of Homotransplants
Comparative histological studies of auto-, homo- acid heterotransplants
J. CHIITNt~
Summary
A histological study of auto-, homo- and heterotransplants in mice, rats and
chickens was undertaken with the aim of determining the characteristics of cellular
infiltration during the healing of homo- and heterotransplants. In homotransplants,
first of all slight round cell infiltration represented mainly by lymphocytes was
observed, which subsequently increases in intensity and becomes very marked.
This round-cell infiltration regularly accompanies the destruction of homotransplants
in mice, rats and chickens. Concomittantly with the development of the round-cell
infiltration thromboscd blood-vessels were observed in homotransplants together
with minute as well as more extensive haemorrhages. The appearance of degenerative
changes in the epidermis in connection with round-cell infiltration and the disinte-
gration of the infiltrating cells themselves may be considered as important, since
from this the specific role of the round-cell infiltration and primarily that of the
lymphocytes can be assumed in accordance with the hypothesis on the transport of
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antibodies by these cells. Granular leucocytes, which do not participate until later,
according to our observations, in local reactions during the healing of homotrans-
plants, are concentrated primarily on desquamating necrotic tissue. In combined
transplants, where skin grafts were transplanted in such a way, that the autotransplant
is placed between two homotransplants or vice versa, the lymphocyte infiltration
and circulatory disturbance were localised to the region of the homotransplant. In
the border region capillary branches transgress from auto- to homotransplants and
vice versa. The heterotransplant reaction to a foreign tissue is also morphologically
expressed much sooner (already 24 hrs after transplantation) and is characterised
by marked exudation and cellular infiltration with a preponderance of granulocytes
which is of different intensity according to the species studied. Degenerative changes
in the epidermis of heterotransplants were already observed 4-5 days after trans-
plantation. Cellular infiltration in heterotransplants becomes qualitatively still
more polymorphocellular - in addition to granulocytes there is an increase in
lymphocytes and the heterotransplant which is already well vascularised on the
3rd-4th day according to observations, contains extensive haemorrhages by the
6th- 8th day and as necrotic tissue it is replaced by surrounding tissue of the host
in the presence of an intensive reaction. Questions of the mechanism of destruction
of homo- and heterotransplants are discussed.
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FOLIA BIOLOGICA
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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cFia~Kaxel~He npoRB~Aazocb, Bo-nepsblx, B ToM, vTO MbIIUKHax ollyxo~h Crocker-a,
Ilepeca~ICexxax c6~tlxcasmi3MCR >xASOTxblivt, AocTllra~a 6o~ree axaxll~~e~bHblx paa-
MCpOB, t3OM B KOATpOJIbHOM M8Tf3pId8JI0, 8 RO-BTOPbTI, B OCJI86JICHLIYI CIIOCOFHOCTl7
K OCp83OB8HHI0 IIMM}~HAbIX BTPJIfOTIIHHHOB IIpOTIIB M61ILi13HbIX 3pHTpOI[LITOB.
B oTa~NUKe oz peay~bTaTOS BxyTpHaapo~hllnesoro c6nH>teHHx y xpbic, xoTOpble
npIIBOR>2T Bolag (1955), MbI xe xa6nx>Aa~x cTO~[b 3xaullTenbxoil paaxHubl s pocTc
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IIINHbIM BHTIII'CHaM MO~CFIO V KpbIC ;I,OOIITbCfI IIE? TOJIbKO B TE9CIILI(? 3MC)pY1OPCHC88,
HO N B pBHHNLI llCpIIOj[ IIOCT~MC~pIIOPOI[O88. 0,[HBIio B OCOH~ CJIy98FIX JjOCTIIP87[OCb
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I[E'pf'CflT,[ICII N ~% C~JIII?ICaBIIIII%CH 1KHBOTHbIX HaCT~'IIaTIa pePpCCCIIH OIiyXOJIH~ II B TOM,
9T0 CllOCO~AOCTb If Ohpa3OB8HHI0 IIMbIyHHbIX aPPJIIOTYIHIIAOB OIS83bIB8JI8Cb TO7IbKO
OCSIB~JIEHHON~ HO Hit I3 O~HO'11 CJIV~IBf', H0 TCpHJIaCb.
Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
JIxTepaTypa
I a ur a x, M.: BQreTaTHBHaH rHOpHJ~x3ai~iiH HfHBOTHbIX HyTeM CO@j(HHOHHx KpOB006paH~eHHH
B Teuexxe aM6pxanbxoro paaBnTxx. LIcn, bAOJIOrHfI 2:267, 1953.
I' a m e x, M.: I7poxB.nexH>; BereTaTxxxoro c6.nxHCexHx B aRaHTagnx Bi>icmxx xcxsoTxbix xa
vyxcepoAxbie axTnrexbi. LIcs. SxOJIOPxx 3:344, 1954.
B i 1 I i n g h a m, R. E., Brent, L., Medawar, P. B.: Actively Acquired Tolerance
of Foreign Cells. Nature 172:603, 1953.
B o I a g, W.: Heterologe Transplantation von Tumoren bei Vorbehandlung der Empfangerticr~
mit Gewebe der Spendertiere wahrend der Embryonalzeit. Experientia 11:227, 1955.
C i n a d e r, B., D u b e r t, J. M.: Acquired Immune Tolerance to Human Albumin and the
Response to Subsequent Injections of Diazo Human Albumin. Brit. J. Exp. Pathol. 36:515,
1955.
H as a k, M.: Vegetativni hybridisace iivoLichu spojenim jejich krevnich ob~hu v embryo-
nalnim v~voji. ~s, biologie 2 :265, 1953.
H as a k, M.: Projevy vegetativniho sbliiovanf v adaptaci vyssiho iivoLicha na cizorod~ anti-
geny, ~s. biologie 3:327, 1954.
Has" a k, M.: Problem p~ekonani nesluLivosti tkani pri homoplastick~ch p~enosech. has. lek.
Les. 94 : ri1, 1955.
H as a k, M.: Vliv intraembryonalnich injekci cizodruhove krve na tvorbu protilatek. I I. Sledo-
vani reaktivity u kachen, hus a perliLek. ~`s, biologie 5 : 5, 1956.
H as a k, M.: The Influence of Intra-embryonal Injections of Foreign Blood on the Formation
of Antibodies. II. Fol, biol. (Praha) 2:48, 1956.
H r a b a, T.: Imunologicke chovani embryonalnich parabiontu mezi krtiitou a slepici. I. ~s. bio-
logie 5 :91, 1956.
H r a b a, T.: Immunological Behaviour of Embryonal Parabionts between Turkey and Hen,
Fol. biol. (Praha) 2:165, 1956.
K o p r o w s k i, H.: Actively Acquired Tolerance to a Mouse Tumor. Nature 175:1087, 1955.
S i m m o n s e n, M.: Artificial Production of Immunological Tolerance. Nature 175:763,
1955,
Woodruff, bf. F., Simpson, L. O.: Induction of Tolerance to Skin Homografts in
Rats by Injection of Cells from the Prospective Donor Soon After Birth. Brit. J. Exp. Pathol.
36 :494, 1955.
Immunological Tolerance of Rats against Crocker's Tumour during
Embryogenesi~s and Postembryogenesis
J. GROZDANOVIL~
Summary
Immunological tolerance of rats against heterogenous cellular antigens was
attained by administering homogenates of mice liver, spleen and kidney during
embryogenesis as well as in newborn rats. White rats and white mice of our own
breed and Crocker's tumour passaged on white mice were used. Subcutaneous
injection of tissue homogenates into rat embryos 4-1 days before birth and into
newborn rats, resulted in immunological tolerance, which was manifested by the
larger size of mice Crocker's tumour in tolerant animals after transplantation as
compared with control material and by a decrease in the ability to produce immune
agglutinins against mouse erythrocytes. (Immunological tolerance was evaluated
at a time, when rats reached 50- 60 g. weight. )
In comparison with intra-embryonal tolerance in rats described by Bolag (1955)
we did not observe such significant differences in the growth of tumours in tolerant
and control animals. It is possible to attain immunological tolerance in rats against
heterogenous mouse cellular antigens not only during embryogenesis, but also during
early postembryogenesis. In both cases, however only incomplete tolerance developed
which manifested itself by a regression of the tumours 10 days after transplantation
even in tolerant animals as well as by the fact, that the ability to produce immune
agglutinins was only reduced, but never completely abolished.
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FOLIA BIOLOGICA
I~ICCJIeJ.[OBaHI~Ift peal{TYIBHOCTYI I(pbICbI IIOCd'Ie BH~'TpYI3apOJ~bILLieBbIX
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Ilocnzynu.tio e peaa>i>~uro 19 Y'I 1956
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Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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ham c corp. (1953).
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~osaJ11I HyI'eM peHMMyHHaauxn c6JIHH{asHlHxcR Kpblc o6eHx cept~il. I{pblcbl cepI3I3 A
peI1MMyHHaxpoBaJlHCb Hpn Bece 6oJIbHIe 150 r, T. e. HocJle Toro, Kax oHx RocTl~trnx
HoJlosoi3 apeJlocTH, a B CepHH B - HpH Bece oxono 150 r, T. e. B HepHOR noJlosoro
coapesaxHR. B cepHt~ A HaM He yRasaJlocb npH cpasxexHH cpeAHHx THTpoB y onblTHOiI
H xoHTpoJlbxoK rpynH Ha6JIIORaTb cTaTHCTH*lecKH axayHMylo paaxHljy (P > 0,5,
T. e. HOB03M0?KHO 6bIJi0 yx{e OTMBTHTb COCTORHHe HMMyHOJIOPH9eCKOTO C67IH?I{eHHR).
B CepHH B MbI yCTflHOBHJIH, iITO COCTORHHe I3MMyHOJIOPI3LI0CI{OPO CCJII3IKOHLIR 0Hj@
OTLIaCTH COXpaHROTCR, XOTR THTp 6bIBaJI BbIHIe, LIeM IIpH HepBOI3 HMMyHH:3auHH, T8K
KaK HpH CpaBHOHHH THTpOB arrJIIOTHHHHOB HOCJIe peHMMyHH3aIjHH MbI eHje HBXOZ[HJIH
CTBTHCTHLIeCKH 3HaLIHMyIO pa3HHIjy: P ~ 0,001.
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
TaC~. 1. TliTp aPPTIOTIIHftHOB ~ KpbIC C N3b1eHeHHOLI pPBHTflBHOCTbtO, I3MntyHli3ftpOB1HHbIX -kPOBHHbIMft T~JIbL~aMI3 FLpO~LIKfl.
a
i s F
s - .~
F ~ i x
a4 s M
F ~ '~ ro
F ~ ~i co a
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
t~uc~yccuR
IIOJIy~ICkiHbIC 3IaMH pe3yJIbTaTbI OTBeLIaIOT j[aHHbIM 1'aIHKa (1955), I{oTOpbIH, -
I{aki n MbI, - ~ McSKBnj[OBbIX napaCHOHTOB (yTKa - KypHl[a) HanIeJI 3HaLIHTeJIbHOe
HapyHICHHe CIIOCOOHOCTn K O~pa30BaHLIIO arrJIIOTHHnHOB. N1bI nOj[TBepH{j[aeM TaKH{e
flpaB3IJIbHOCTb HarOJIIOj[eHHH (I'ameK H I'pa6a 1955), uTO yrxeTexxe o6paaosaxHx
nMMyHHbIX al'1'JIIOTnHI1HOB B yCJIOBnHX Me?KBnj[OBOPO C6JII31KeHHx HBCTynaeT HC TOJIbKO
nOCJ[e HMMVHn:3aI[HH KpOBHHbIMH TeJIbI[aMH TOPO )1{C j[OHOpa (MeH{jty HpOzIHM, HapTHepa
n3 napa~OH0:3a), HO Li IIOCJIe xMMyHH3aI[HH TeJIbI[aMH j[pyrHX 0006eH, npnHaj[JIe-
iKaH[HX K TOMy iI{e EnOJI01'HLICCKOMy BHj[y, KaK N j[OHOp, KpOBHHble TenbL[a KOTOpOTO
HCHOJIb30BaJInCb j[JIx BHyTpn3apoj[bIIIIeBbIX I3H'beKIjHH.
L~HaJIOTHikHble pe3~'JIbTBTbI nOJIyLIHJII3 HOCJIe BHyTpI33apOj[bIIIICBbIX BHpbICKIIB8HI3H
KpoBLt j[pyroro Bnj[a (KypHI[a - Ilxj[ei3Ka) Simonsen (1955) H I'a>IIex (1956a).
[lanpoTHB, Simonsen-y (1955) H I'pa6a c corp. (1956), npH ToH aKe McTOj[nxe, xo,
1{oxeuxo, HpH ,[pyroii KoM6HHauNN (Hanp., y Simonsen-a KypHI[a - rycb), xe
y;[asaJlocb sbiasaTb c6Jlnx{exNH. Oj[xaxo I'pa6a (1956) j[o6HJICx y xyp-Hapa6HOxTOB
c nxj[e~ixaMn noJiHOro Hoj[asJlexHH peaKTLlBxocTH. PTO oTKpbITLIe - ej[Hxc'rBexxblu
csoero poAa cJlyikai3 B o6JlacTn re'repocepoJlorHUecKIIx oTHOInexHti, Korj[a yRanocb
IIOTIHOCTbIO nO~aBHTb peaKTHBHOCTb. 113 npxBej[eHHbIX (~aKTOB OLIeBHj[HO, iLTO Cykue-
cTByIOT BLij[OBble pa:3JInLInH B 3(~(~eHTHBHOCTH I4MMyHOJIOPI3LieCKOTO CCJILIHCCHIIx.
WOOdtUSI H S1mpSOn (1955) HaHIJIH aHaJlOrx~lHble H3MCHCHI3H peaKTHBHOCTI3
y KpbicHT B paxxlix cTaj[liHx HocTaM6pLlorexeaa nocJie snpbicxLlBaxHH BaBecN KJIeTOK
11:3 rOMOI'eHH3HpOB8HHbIX OpraHOB. 1~1M Vj[aJIOCb I[aCTOJIbKO C~JIx3HTb j[Ba IIJICMCHI-i
Kl).bIC, iITO I{O}I{Hble rOMOTpaHCHJIaHTBTbI, IIepeCaH{eHH~,Ie B aj[aHTaL[I30HHbII3 Hepl3oj[,
npNaKNBaJIn HopMaJlbxo.
Bolag (1955) c6JlnaKaJl I{pblc c MbIIIIaMH npH noMOluN BHyTpHaapoj[bIlIIesblx
B(IpbICI{HBaHffiI KpbICaM rOMOPCHH3HpOBaHHbIX OpraHOB MbIIIIeII. ~i' CJIH B TBileHI3e
IIOCT3M~pI30I'eHe3a OH IlepeCa>I{HBaJI 3THM KpbICBM MbIIIIHHVIO CapKOMy Crocker-a,
To oxa pocJia ropaaj[a aKCnaxc.HSxee, ueM B KoxTpoJle, xoTx BpeMH BbIaKHBaH1Ix
OIIyXOJIn (pe~lb n~BT O Me53{Bnj[OBOH I{OMCHHaI[HH MbIIIIb - KpbICa) OCTBBaJIOCb
HCH3MCHHbIM. IjOBnj[nMOMy, 3j[eCb nMeJIO MCCTO LIaCTI'IL1HOe IIOj[aBJICHHe peaKTHBHOCTH.
flaC HHTCpeCOBaJIa IIp06JICMa IIMMyHOJIOrYILIeCKOPO C~OJIH>1{CHHx MJIeKOHLLTaIOII[LIX
13 paMIfaX 1'CTepOCepOJIOTH'LeCKHX OTHOHICHHFi. KpbICa IIpej[CTBBJIHJIBCb H8M yj[OOHbIM
o~?beKTOM ~JiR onblTOB, Bo-nepsblX, BBxj[y ee cpaBHHTeJ~bxo Bblcoxol~ ycTOH~xsocTH
110 OTHOHICHnlO K HH(~)eKI[nLI n HCI[pOj[OJI}I{HTeJIbHOCTH CC IIepI30j[a CepeMCHHOCTH (3Tn
IipeHMyLI[eCTBa 1{pbICbI KaK JIa~OpaTOpHOPO H{HBOTHOPO OTMeiIaeT n Nicholas -
1925), a Bo BTOpblx, 11 Ho'ro:~iy, uTO xBJlexne HMMyxoJlorHUecxoro c6JIHx{exHx j[o cNx
IIOp HC nCCJICj[OBaJIOCb B TOIi KOM6xHaL[HH, KOTOpOH IIOJIb30BaJIILCb b1bI: KpbICa-
I{pOJILLK. KpOMe TOrO nMMyHOJIOTH~IeCKOe C6JIII7I{eHHe y biJICKOnHTaIOII[LIX HC HCCJIej[O-
13aJIOCb RO CHx nop C IIUMOII[bI0 CepOJIOTHHeCKHX TCCTOB.
-lOJIyiICHI1bI8 HBMn 1[pn peI1MMyHn3aL[nn C6JIY1?KaBHInxCII KpbIC pC3yJIbTaTbI nOKa3bI-
BaIOT, 9T0 COCTOHHiie n:3MCHHBIDeHCx peaKTIIBHOCTH (nMMy'HOJIOrHLIeCKOI'O COJILIH{eH13H)
coxpaxxen;x, - s yCJIOBIIHx xalHero onblTa, - BnJIOTb j[o nepnoRa noJlosoro coape-
BaHHx (T. e. ;u) 150 r seca).
MbI HCCJICj[OBaJIri B03MOi1{HOCTb C03j[aTb }~ KpbIC nMMyHOJIOrii~leCKOe C6JIH?I{CHYIC
110 OTHOIIIeHHIO 1{ KpOBAHbIDi TeJIbI[aM KpOJInKa. ~. IIOMOIL[bI0 MCTOj[a BHyTpH3apOj[bI-
[HCBbIX BnpbICI{I1B8HNIi HaM yj[aBaJIOCb yMepxTb peal{TIIBHOCTb KpbICbI B nepLloj[
nocTaM6pnorexe3a - B cMblcJle noHH;KexHx. cnoco6xocTH K o6paaosaxHlo arrJlloTn-
HHHOB npOTHB KpOJLIt~ibnX KpOBHIIbIX TeJIeI[. THTp y C6JIH5KaBIHI3XCx KpbIC 6btsaeT
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
HNi3ie B Cp$BHOHNLI C KOH1'pOJIE'~M, Ilpi~hlOM p83I~NLja OK83bIBaCTCF1 ('TBTNCTN90CICN
3HayNMON. ~CT0CTB0HHbI0 8I'PJIIOTNHNHbI IIpOTNB ICpOJINtibNX HpORRHI>IX 'f0JI0I( I[~Il
ABIIINX OIIhITBX y KpbIC HaNJjOHbI HO 6bIJIN. BbI3bIB8BIiI08CH HaMN NMbIVNOJIOI'N>IECKOe
CGJIN?ICCHNO y ICpbIC~ IIpH OHNCBHHbIX HBMN MOTOj[IhIOCitNX NprICMBX, COXpaHflETCFI j(U
nepNOAa Ho~osoro coapesaHNR.
P a m e r,, M.: Ilapa6no ~ n'rnil no npenru amu"pnona.nenoro paanrrTnx. ~Icn. Grro~~oa~I~n 2:29,
1953x.
P a m e K, M.: BereTaTrannax rra6pnunaagnn .xnnoTRr>>x nyTeM coe;~nRenr~n f:ponoofipautcrrnsr
B Te9l'HLIe 8M6pnORaJIbHOPO paBBnTIdH. ~CJr, ~noJlOrnH 2 :267, 1953F,
B i 1 1 i n g h a m, R. E., Brent, L., Medawar, P. B.: Actively Acquired Tolerance
of Foreign Cells. Nature 172:603, 1953.
B o 1 a g, W.: Heterologe Transllant~.tion von Tumoren bei Vorbehandluug der Empfangerticrr?
mit Gewebe der Spendertiere wahrend der Embryonalzeit. Experientia 11:227, 1955.
F r e n z 1, B., H as e k, M., H a s k o v a, V., Hraba, T.: Irnunologicke vztahy
u embryonalnich parabios mezi kachnou a slepici. I. (~s. biologic 4 : 1, 1955.
H as e k, M.: Parabiosa ptaku v embryonalnim vyvoji. ~s. b.ologie 2:25, 1953x.
H as e k, M.: Vegc tativni hybridisace zivo~ichu spojenim jejich krevnich obehu v embryonalnim
vyvoji. Cs. biologic 2:265, 1953b.
H a s e k, M.: Vegetativni hybridisace u iivo~ichu. Praha 1954.
Hasek, M., Hraba, '1'., Benes""ova, H., Hlava~kova, 1I.: Irnunologicke
vztahy a embryonalnich parabiontu mezi kachnou a slepici. II. ~s. biologic 4:135, 195~i.
H as e k, M., H r a b a, T.: Immunological Effects of Experimental Embryonal Yarabiosis.
Nature 175:763, 1955.
Has" e k, M.: Vliv intraembryonalnich injekci cizodruhove krve na tvorbu lrotilatek. II. Sledo-
vani reaktivity u kachen, hus a perli~ek. G`s, biologic 5 : 5, 1956x.
H as e k, M.: The Influence of Intra-embryonal Injections of I~'oreign Blood on the Formation
of Ant; bodies. II. Fol. biol. (Praha) 2:48, 1956x.
Has" e k, M.: Otazky imunologickeho sblizeni. PLC 95:505, 1956b.
Hraba, T., IIaskova, V., Lengerova, A., Vojtiskova, M.: Vlivintra-
embryonalnich injekcf cizodruhove krve na tvorbu protilatek. I. Sledovani reaktivity u slepic.
~s, b~ologie 5 : 1, 1956.
Ilraba, T., Haskova, V., Lengerova, A., Vojtiskova, M.: The Influence
of Intraembryonal Injections of Foreign Blood on the Formation of Ant~bodic s. I. Fol. biol.
(Praha) 2:43, 1956.
Hraba, T.: Imunologicke chovani embryonalnich parabiontu mezi krutou a slepici. I. (s. bio-
logic 5:91, 1956.
Hraba, T.: Immunological Behaviour of Embryonal Parabionts between Turkey and Hen.
Fol. biol. (Praha) 2:165, 1956.
N i c h o 1 a s, J. S.: Notes on the Application of Experimental Methods upon Mammalian
Embryos. Anat. Rec. 31:385, 1925.
Simonsen, M.: Artificial Production of Immunological Tolerance. Nature 175:763, 1955.
Woodruff, M. F., Simpson, L. O.: Induction of Tolerance to Skin Homografts in
Rats by Injection of Cells from the Prospective Donor Soon after Birth. Brit. J. Exp. Pathol.
36:494, 1955.
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The Reactivity of Rats after Intra-embryonal Injection
of Foreign Blood Cells
Changed reactivity in the sense of a disturbance of the ability to produce antibodies
has been described after experimental embryonal parabioses and intra-embryonal
injection of foreign blood during postembryogenesis in experimental animals. The
possibility of evoking a similar change in the reactivity (immunological tolerance) of
rats against rabbit blood cells was investigated. Amounts of 0.15 - 0.2 ml of 40?~0
suspension of rabbit blood cells were injected into rat embryos 1- 5 days before birth.
During postembryogenesis, the presence of natural heteroagglutinins in the serum of
young rats previously injected intra-embryonally was investigated on reaching body
weight 40-100 gm. These animals were then immunised and the titre of immune
heteroagglutinins was determined. Natural agglutinins in rats against rabbit erythro-
cytes were not found in our experiments. In young rats intra-embryonally injected
a change of reactivity was found during postembryogenesis. The titre of immune
agglutinins in rats with changed reactivity is lower in comparison with the controls.
This difference is statistically significant.
A relatively high titre was observed in four of the experimental rats where it was
assumed that an incomplete intra-embryonal injection of rabbit blood cells had been
performed, which led to such an insignificant change in reactivity during postem-
bryogenesis, that it was not possible, under our experimental conditions, to prove its
existence.
Our results corroborate the findings of Hasek and other authors about the possibil-
ity of evoking changes in the reactibility-immunological tolerance-by means
of intra-embryonal administration of a foreign cell antigen.
It was found that the immunological tolerance acquired under our experimental
conditions lasts to sexual maturity.
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The Influence of Protein Deficiency and Excess in the Diet
on Immunity Response
7.. TIt\'fiA
Institute of Biology of the Czechoslovak Academy of Science, Department of Microbiology, Praha
Because of its practical and theoretical importance the influence of the composition
and amount of food received on defence mechanisms of the organism is often discussed.
It has been clearly demonstrated in a number of experimental works that a diet
deficient in calories and vitamins lowers the ability of the organism to withstand
bacterial infections. After the demonstration of the protein character of antibodies.
the importance of protein metabolism for the defence of the organism became evident.
A number of studies analysed the effect of the amount, composition and quality of
proteins in food both on antibody formation itself and also on other defence mechan-
ism. The majority of authors studying this problem demonstrated a significant
decrease in antibody formation and a general decrease in natural and acquired
resistance to infections and intoxication in experimental animals fed on a low protein
diet (e. g. Cannon, Chase and Wissler 1943, Cannon 1945, Berry-, Davis and Spies
1945, Wissler, Woolridge and Steffee 1946, Forni 1952, Vershilova 1954, Klimentova
1954 and others). Other authors, however, especially in earlier work (e. g. Zilva 1919,
Lange and Simmons 1923) or in work on clinical material difficult to analyse (e. g.
Bieler, Echer, and Spies 1947) could not demonstrate a significant fall in antibody
formation or general resistance to infection in organisms deficient in proteins.
Guggenhaim and Buechler (1946 and 1948) conclude from their experiments that
humoral defence mechanisms are more sensitive to protein deficiency than cellular
mechanisms. Robertson and Doyle (1936-1937) found that rats fed on a diet with
animal proteins were considerably more resistant to bacterial infections than rats
fed with plant proteins.
It can be concluded from the above that long-term feeding with low protein diets
causes decreased antibody formation. The few clinical experiments carried out on
cachecticpatients with various diseases (Bieler, Echer and Spies 1947, Balch 1950)
indicate, on the contrary, normal serological characteristics and even increased
antibody reactions to antigenic stimuli.
Hitherto, however only the effect of protein deficiency has been studied. The
influence of high, excessive protein diets has been completely neglected. In this cowr-
try Poupa and his team is studying the influence of low protein, and high protein
diets on various physiological functions. He demonstrated (Poupa 1954) that rats.
especially during the phase of most rapid growth, grow best when fed on a diet con-
taining amedium amount of protein. Lat and Faltova (1954) showed that regulation
of protein intake is relatively fine as far as quantity is concerned and corresponds to
the so-called protein optimum in agreement with the optimum protein concen-
tration for growth as found by Poupa. Faltova, Poupa and Servit (1955) ascertained
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Per
1.000 g
.
% of
total v
olume
i
Diet
~
t
"
m
~
~
m
ti
I
b
c
.~ i
~
?~,
~
O
?~
o
a
A
a
o
~
v
Z
A
a
.
o
~.,
L15
240.0
500.0
60.0
3.0
30.0
7.0
88.0
16.5
5.5
50.0
23.2
48.1
8.8
L18
490.0
250.0
60.0
3.0
30.0
7.0
88.0
16.5
5.5
50.0
42.9
27.1
8.9
Llg
35.0
705.0
60.0
3.0
30.0
7.0
88.0
16.5
5.5
50.0
6.7
65.3
8.7
that both excess and deficient dietary protein increases seizure susceptibility to
electrical and sound stimuli in mice in comparison with animals fed on a diet contain-
ing medium amounts of proteins, optimal for growth. Lat and Faltova (1955) found
the same optimal protein concentration for the power of differentiation of the CNS.
A high protein diet causes an increase in inhibition, a low protein diet an increase
in excitation.
In this paper changes in some immunological reactions of rats are studied when
the latter are fed on short-term or long-term diets containing a low, optimal for
growth and high concentration of proteins.
Experiments were carried out on two groups of 90 growing male Wiatar rats (bred at the farm of the
Czechoslovak Academy of Science) aged three months and weighing on the average 240-250 g. From
the time of weaning up to the beginning of the experiment the animals were given a standard Larsen diet.
The rats were divided into three equal groups and kept six in one cage. Individual groups were fed on
three different, practically isocaloric, diets of constant composition and differing only in the proportion
of proteins (casein) and carbohydrates (wheat starch). Thus the final percentage of proteins in the three
diets was 6.7, 23.2 and 42.9 respectively. (Diets described by Poupa were used v. table 1.) Animals had
free access to food and water. Food and water were changed regularly at the same time every day in
order to disturb the animals as little as possible. Throughout the experimental period food consumption
Fig. 1. Short-Term Administration of 20
:Diets. Intake in the various groups.
y: Average intake in g. per rat. x: time
in weeks.
L15 (23.2 ?~o proteins) full line,
L18 (42.9 ?~~ proteins) interrupted lino, ~ 5
Lis (6.7 ?:~ proteins) dotted line.
5 !0 15
was measured daily (figs. 1 and 2). Intako was approximately the same in all groups so that caloric
Intako may be considered equal in individual rats of all groups. It follows that inequalities in growth and
other differences are due to the different compositions of the diets. Rats were weighed regularly once
a week (fig. 3 and 4).
One month (in short-term) and 4 months (in long-term experiments) after the beginning of
the experiment, blood was taken from all rats from the tail vein, after cutting off the end of the
tail, for the determination of complement levels and for carrying out control agglutinations
before immunisation. All control agglutinations were negative in all dilutions. In addition, total
proteins were determined in the same blood using the refractometric method. Average values
for serum proteins in short-term experiments were 7.00% for the medium protein group, 5.98
for high protein group and 5.59 % for the low protein group. The decrease in total serum proteins in rats
fed on the low protoin diet is in agreement with the findings in the literature (Krebs 1946, Bieler,
Echer and Spies 1947, Metcoff, Favour and Stare 1945 and others). Average values for total serum
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proteins in long-term (8 months) experiments were 5.85?~o for rats on the low protein diet, i. e. a. value
in agreement with the reports in the literature and our own experiments. For the high protein group the
value was 6.91% for the medium protein group 7.04%, i. e. practically the carne for both groups. One
month after the beginning of the experiments half the number of rats fed on the different, diets was
immunised i.p, at intervals of two days with 6 doses of Salmonella paratyphi B inactivated by heat
Fig. 2. Long-term Administration of Diets. Daily intake of diets in g. (y) pe,r weol: per rat.
x: weeks of the experiment.. Lis, Lrs and Lrs (as in fig. I ).
(5 X lOs microorganisms per immunising dose). After the end of immunisation blood was t;rken frour the
tail vein on tho 4th. 7th, 10th, 14th, 2lst, 28th and 35th day and agglutinating :mtibodiee were
determined. On the 4th month after the beginning of the experiment, rats wore infocted in 9 groups and
bacteraemia and the survival rate were determined.
In the long-term experiment, at the end of the ith month, half the number of rats was immunised in
the same way as before and on the 5th, 7th, 10th, 14th, 21st, 28th, 36th, 42nd and 49th day after immu-
nisation agglutinating antibodies were again determined. After that infection experiments wero msrde
in 12 groups and bacteraemia and the survival rate were determined.
Titration of complement was caried out in the usual way using commercial haemolytic amboceptor.
Only for greater precision, dilution of the complement was in decreasing series per 0,03 ml. of the serum
under investigation which was diluted 1:10. Intensity of haemolysis was determined in the supernatant
fluid after centrifugation using a colorimeter and a green filter of wave length 530m?. Results were
expressed as a precentage of haemolysis using a curve obtained from a ?~ diluted haemolytic series of
the haemolytic system used in a given experiment.
Agglutinating antibodies were determined using the cold agglutination test in an refrigerator
( ~- 2 to 4? C). Readings were taken after 2,4 and 6 days.
Salm. paratyphi B suspended in 0.2 ~~ agar was used for infection. The DL 100 was determined
Fig. 3. Short-Term Administration of
Diets. Growth curves. y: average weights
in g., x: days after the beginning of the
experiment. Statistical evaluation on the
99th day (Student's t-test shows differ-
ences between Lrs and Lrs and Lrs arc sig-
nificant (P < 1s,!ss) but between Lrs and
Lre insignifcant (P < 10 jr,). Lrs, Lrs, Lrs
(as in fig. 1).
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per 100 g. normal rat (5 x 108 microorganisms per 100 g.). Administration was intraperitoneal. Experi-
mental immunised and non-immunised rats were used in groups in which infecting doses were changed
as necessary. Bacteraemia, indicating transfer of bacteria from the peritoneal cavity into the blood was
determined together with the rate at which blood was cleansed. Blood in amounts of 0.4 ml. was taken
from the tail vein 1, 3 and 6 hours after infection into 0.1 ml. 5% natrium citrate. Dilutions were 1:50,
Fig. 4. Long-term Administration of Diets. Growth curves. y: average weights in g. x: weeks after
the beginning of the experiment. Differences between all three groups (Student's t-test) significant
to P < 18/x, Llb, L18, I.~s (as in fig. 1).
1:500 and I :5000. Culturing was carried out on End's medium. The number of microorganisms was
determined from the average of 4 cultures. Numbers of microorganisms given in the table are calculated
for 1 ml. blood. Survival of rata was observed for 7 days.
Spontaneous deaths of rats during the short-term diet experiments were insignificant. Only 1 rat in
each group died. During the long-term experiments a large number of deaths was registered in the low
protein group. On the 2nd and 4th month one rat died in this group in the fifth and sixth months two
rata died and in the seventh and eighth months three rata died, so that altogether only 18 rata out
of 30 survived. The cause of death was spontaneous infections, mostly of the upper respiratory tract.
On the other hand no rats died in the medium and high protein diet groups.
As is evident from fig. 5, the largest amount of complement was present after one
month on the experimental diets in rats fed on the medium protein diet, the amount
was less in animals on the high protein diet and least on the low protein diet. Using
50% haemolysis, the difference between the medium and low protein groups is
slightly significant. Significance is high on 80% haemolysis. The difference between
both these groups and the high protein group is not significant.
After four months on the experimental diets the level of complement was very
low in the low protein groups (fig. 6). Differences between this group and the medium
and high protein group are highly significant on 50% and 80% haemolysis. Comple-
ment levels were nearly identical in the medium and high protein groups. Differences
are on the border-line of significance with 50%haemolysis and are not significant with
30%haemolysis.
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The level of agglutinating antibodies in the short-term experiment (fig. 7) shows
that immunisation gives rise to titres significantly higher in the medium protein
group than in both the other groups. The difference between the low and high
protein groups is not significant.
Q0401
0,030
0,020
0,010
50?6
'i
80%
~.,,, ,,,, BxEE
0,040
8030
Q020
D 010
i
80
Fig. 5. Fig. 6.
Fig. 5. Short-term Administration of Diets. Amount of complement (average from 3f1 rats) in absolute
amounts of serum necessary for 50% and 80% haemolysis. Circles indicate number of cases in which
oven the highest amount of serum used (0.045 ml.) did not cause the tested %haemolysis. For the
figure in such cases the next highest amount of serum was taken (0.05 ml.). Wilcoxon's /3 test was used
for statistical evaluation.
50% haemolysis: Li9 white columns 0.029; Lr5 perpendicularly shaded columns 0.021; LIB horizontally
shaded columns 0.027. 80% haemolysis: LI8 0.038; L15 0.026; LIB 0.034.
Fig. 6. Long-terrn Administration of Diets. Amount of complement (average from 30 rats) in absolute
amounts of serum necessary for 50% and 80% haemolysis. Circles indicate number of cases in which
even the highest amount of serum used (0.045 ml.) did not cause the tested % haemolysis. For thc?
figure in such cases the next highest amount of serum was taken (0.05 ml.). Statistical evaluation by the
Cochran-Cox approximation of the Student t-test for the difference of the two averages.
50% haemolysis: LI9 (white columns) 0.018; L15 (perpendicularly shaded columns) 0.010; L18 (horizon-
tally shaded columns) 0.014. 80% haemolysis: LIB 0.046; L15 0.026; LIB 0,026.
?56
f28
6S
32
16
8
4
J: ?
~ ~ ~o r4 2r 2s 3s
Fig. 7. Short-term Administration of Diets. Agglutinating antibody formation. y: Average titres
of agglutinating antibodies of individual groups. x: days of blood collection. after completion ol~
immunisation. Statistical evaluation by Wicoxon's ~-test. Up to the 21st day differences between L15 and
LIB are not significant, and up to the 28th day the same holds good for LIB and LI;. Differences betweon
LIB and L19 are insignificant throughout. Numbers indicate numerical values of titre averages.
LIB (white columns):
L15 (perp. shaded columns):
LIB (horizon. shaded columns):
9.3
- 24.5
- 48.0
- 6.1
13.13
-- 21.2
- 24.5
40.0
- 61.7
- 116.8
- 125.7
- 24.0
- 49.9
- 32.0
11.4
- 24.5
- 43.0
- :59.7
- 17.8
- 2L1
- 30,8
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't'able 2. Survival of Tnfection. Rows indicate suacessive groups taken into experiment. Statistical
evaluation: Wilcoxon's ~-test
Short-term Administration of Diets
Grou
No. of
Dose
Deaths in hours after infection
( No. of
p
rats
6 124 48 72
96 1128
114411.68
survivors
_I
Llb
3
7DL 100
1
1
1
--
0
(23.2% protein)
3
7 DL 100
1
1
1
immunised
4
7DL 100
2
2
4
7DL 100
4
Lre
3
7DL 100
2
1
(42.9% protein)
3
7DL 100
1
1
1
immunised
4
7 DL 100
4
4
7DL 100
4
L39
3
7DL 100
3
0
(6.7% protein)
3
7DL 100
3
0
immunised
4
7 DL 100
1
3
0
4
7 llL 100
1
2
1
Lls
3
1 DL 100
3
0
(23.2% protein)
3
'/4 DL 100
2
I
0
non-immunised
3
2/a DL 100
1
2
2
z/3 DL 100
2
3
2/3 DL 100
1
2
L18
3
1 DL 100
1
2
0
(42.9% protein)
3
3/4 DL 100
2
1
non-immunised
3
2/3 DL 100
1
2
2
z/3 DL 100
1
1
4
2/3 DL 100
2
1
1
LAB
3
1 DL 100
1
2
0
(6.7% protein)
3
3/4 DL 100
3
0
non-immunised
3
2/3 DL 100
3
0
2
a/3 DL ] 00
1
1
3
~/3 DL 100
3
~
0
S12
256
12B
64
32
16
B
4
12
Fig. 8. Long-term Administration of Diets. Agglutinating antibody formation. x: days after
immunisation when blood was taken. Crosses indicate titres of individual rats. Wiccxons ~-test used.
Numbers give exact values of individual averages.
L19 (white columns):
46.1
- 28.0
- 10.4
- 33.6
- 156.4
- 49.7
- 45.3
- 30.2
- 15.4
Lrb (porp. shaded columns)
17.6
- 12.0
- 8.8
- 41.6
- 192.0
- 40.0
- 38.6
- 58.1
- 61.8
L18 (horizon. shaded columns) 21.8
- 9.6
- 8.0
- 40.5
- 100.5
- 48.5
- 104.0
- 79.4
- 46.4
311
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In the long-term experiment the levels of agglutinating antibodies show nostrik-
ing difference in the individual groups (fig. 8). The non-significance of the difference
is confirmed by statistical analysis. Differences are significant at the Y < 5% level
only between the low and medium protein group on the 5th day and between the
medium and high protein group on the 21st and 35th day. The survival rates (tab. 2)
show that animals fed on a low protein diet for short periods had a decreased
resistance to infection. This decrease, as manifested by a greater and more rapid
death rate, is highly significant in immunised rats (Wilcoxon ~-test) while it is only
on the border-line of significance in non-immunised rats. There was no difference ill
the resistance of the medium and high protein groups. In the long term experiments
(table 3) there were no differences between the three groups. There was, however,
a significant difference between immunised and non-immunised rats in both experi-
ments.
Table 3. Survival of Infection. Rows indicate successive groups taken into experiment. Statistical
evaluation: Wilcoxon's ~-test.
Long-term Administration of Diets
No. of ~
Group
rats
-
Dose
Deaths in hours after infection
_ ___ - - _ _ -
3 6 9 1 12 i 15 18 21 24 48 I i 2
No. of
survi-
vors
Lls
~
2
1 DL 100
-
~
~
--
~
'l
(23.2?o prot.)
2
3 DL 100
I
1
~i I
immunised
3
4 DL 100
:
i
3
2
10 DL 100
~
~
.~, ~
I
0
'~
3
10 DL 100
; '
I
;
1
1
i 1 I
I 0
3
8 DL 100
it
~
~
i
1.
1
1 I
0
L1e ~
2
1 DL 100
~ .,
(42.9% prot.)
2
3 DL 100
'
~ 2
immunised
~ 2
4 DL 100
~ ~
~
I 2
3
10 DL 100
i i
~
i
l
~ ~
2
3 i
lODL 100
,
i
1
1
i t
0
I
2
8 DL 100
~
~
I
I
1; I
' 0
2
1 DL 100
~
,
~
~ ~I
1
1
j
2
2 DL 100
~
i
2
2
3 DL 100
~
2
2
10 DL 100
1
1
0
L15
?2
I llL 100 ~
1
1
0
(23.2% prot.)
2 ~
~/z DT. 100
~
2
non-immunised
3
3/4 DL 100
3
2
1 DL 100
1
1
3
1 DL 100
I
1
I
1
I
3
1 DL 100
2
I
0
I
Lle
2
1 DL 100
1
1
i 0
(42.9% prot..)
2
i/2 DL 100
1
I 1
non-immunised ~~
2
3/a DL 100
i
2
'~
3
1 DL 100
~
2
~ l
0
3
1 DL 100
_~
~
1
2
~,
3
1 DL 100
I
'
~ ~
~ I
1 '~
~
~~ l
L18 ~
S I
1 DL 100
i
1 '
i
~ l
~
0
(6.7?/o prot.) I
2 ~
~
i/z DL 100
I
~
2
non-immunised I
2
3~a DL 100
~
~ 2
2
1 DL 100
~ ~
~
~ 1
i
~ l
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7'ablo 4. 13acteraemia 1, 3 and 6 hours after infection in immunised and non-immunised rate of different
dietary groups. Figures give the average number of microorganismu per 1 ml. of blood. Statistical
evaluation: Wilcoxon's ~-test.
Short-term Administration of Diets
?~~~ Protein ~ 1 hour
~
~
3 hours
6 hours
-
115
(23.2% prot.) 3,053
53
912
L '
~
(42.9% prof.) 2,471
147
80
~
Leg ~
~"
(Fi.7% prot.) 14,192
31,512
162
~ \
1
1.15
'~
(23.2% prot.) 247,719
419,678
88,988
7
I'18
~
(42.9?% prot.) 234,660
719,517
75,961
0
6 7?,~ prot.) 545,342
202,812
65,729
T
I
Table 5. Bactex~aomia 1, 3 and 6 hours after infection in immunised and non-immunised rats of different
dietary groups. Figures give the number of microorganisms per 1 ml. of blood. Statistical evaluation:
Wilcoxon'a ~-test.
Long-term Administration of Diet
j~ Protein 1 hour 3 hours 6 hours
--- -
- -
I
Lls
i
,~
~
(`23.2% prot.)
12,546
734
107
I.
~
(42.9% prot.)
2,971
1,220
1,500
~
L
I
((i.7% prof.)
2,009
1,025
4S7
I'15
(23.2% prot.)
i 157,995
117,970
92,490
L18
~
(42.9% prot.)
201,880
138,835
100,633 i
Lls
(6.7?,/? prof.)
132,208
132,575
21,2:10
Table 4 gives differences in the number of bacteria in the blood 1, 3 and 6 hours
after infection in the short-term experiment. In agreement with ~terzl (1954) who
demonstrated that transfer of bacteria from the peritoneal cavity into the blood
stream and disappearance of bacteria from blood differs considerably in immunised
and non-immunised rats, the present results show the same picture. Differences
are statistically significant using Wilcoxon's ~-test. Differences between the three
dietary groups in both short-term and long-term experiments (tab. 5) are not
significant.
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It has been possible to demonstrate in agreement with the majority of the
reports in the literature that complement levels, antibody formation and natural
and acquired resistance to Salmonella paratyphi B infection are all decreased in
protein deficient rats. When evaluating results in protein deficient animals it is
always necessary to take into consideration the total amount of protein in the diet
and the species of animal used. In the present experiments the author tried to
preserve the necessary minimum of proteins in order not to kill the animals by
a simple protein deficiency. A protein content of 6 - 7 % was chosen, as one of 9 %,
according to Guggenhaim and Buechler (1948), already prevents the appearance
of considerable differences in bacteriocidal and phagocyte activity in comparison
with normally fed rats (18 % protein). It is therefore evident that in comparison
with experiments using very low protein diets (Guggenhaimer and Buechler 1948,
3%, Cannon, Chase and Wissler 1943, 1%, Cannon, Wissler, V4'oolridge and Bendit
1944, 2 %, Wissler, Woolridge, Steffee, Cannon 1946, 0.9 % and 1.9 %) the diet
used here did not cause such extensive decreases in antibody formation and
resistance. The animals in the experiments quoted were on the border-line of exi-
stence. It is a drawback of most work in this field concerning the effect of the diet on
the organism that usually neither growth nor weight curves are given and in most
cases it is not stated how far animals died spontaneously. This would indicate whether
animals were affected as a whole by the diet, which, in our opinion, is very important
for comparison of results from different work. Another disadvantage of some work
is the use of diets that differ only little from each other (Schneider, Webster 1945,
Forni 1952, Berry, Davis and Spies 1945) so that results depending on a large
number of factors can hardly elucidate the basic effect of individual components
of the diet and again make a comparison of different work impossible. The time for
?~~ _~~ /I
Fig. 9. Short-term Administration of Diets.
Relation between specific antibody formation
and growth rate. Average growth curve of
the medium protein group (full line). Aver-
ages from the 5 heaviest rats from the lo++~
protein group (dotted line) and from the
high protein group (interrupted line): y:
weight in g. x: days From the beginning of the
experiment.
which a diet is given is also discussed insufficiently. In the majority of experiments
diets were administered for 1, 2 and 3 months, rarely for longer periods. The experi-
ments of Metcoff, Darling, Scanlon and Stare (1948) showed that ashort-term
protein deficiency (10 days) and further continuation of this diet did not cause
suspension of antibody formation although there was a total decrease in serum
proteins and therefore also in y-globulin. This work and the work of Bieler, Echer
and Spies (1947) demonstrate that the level of specific antibodies is not directly
dependent on the total amount of serum proteins present.
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The results in rats fed on the high protein diet for a short period are interesting.
In those rats antibody formation is significantly decreased but resistance to infection
is the same as in the medium protein group. In contrast, survival is low in the low
protein group. Optimal production of specific antibodies occurs, in agreement with
Poupa, on the so-called protein optimum in the diet. This tendency is also evident
in the complement levels, although it is not statistically significant. The total
amount of proteins in the blood serum is probably of importance in this case. The
protein optimum is most obvious in its effect on growth. That is why it was attempted
to correlate optimum growth and specific antibody formation in the short term
experiments. In the first place, average growth curves of rats on the medium protein
diet were compared with curves of the five heaviest rats of the low and high protein
groups (fig. 9). No differences were evident between these artificially formed groups.
It appears that there are no considerable differences within individual groups when
average agglutinating titres of all groups are compared with averages of those titres
in the five heaviest rats of each group (fig. 10). This indicates that immunological
characteristics of individual groups are not due to growth rates.
How can decreased antibody formation be explained in the high and Iow
4 - P f0 14 21 28 33
Fig. 10. Short-term Administration of Diets. Average agglutinating titres compared with agglutinat-
ing titres of the 5 heaviest rats in each group (y). x: days when blood was taken after the end of
immunisation.
Curves: 1-L15 (23.2% proteins) average from the 5 heaviest rats
2-Llb
(23.2% proteins) average from 30 rats
3-L18
)42.9?o proteins) average from the 5 heaviest rats
4-L18
(42.9% proteins) average from 30 rats
5-L19
(6.7% proteins) average from the
5 heaviest rats
F-L19
( 6.7% proteins) average from 30
rats
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protein short-term groups ? The experiments of Wissler, Wooldridge and Steffee
(1946) and Wissler, Woolridge, Steffee and Cannon (1946) demonstrate that short-
term feeding of rats with a high protein diet or a diet containing large amounts of
amino-acids several days before immunisation causes considerable increase in anti-
body formation in rats previously fed on a low protein diet. This indicates that th.e
mechanism of antibody formation is not affected, and leads to the conclusion that
the decreased formation of antibodies is due to exhaustion of protein reserves or to
insufficient supply of amino acids in the diet. This is the most usual explanation of
this phenomenon. The fact, however, ascertained from our experiments, that
a high protein diet also causes a decrease in antibody formation, rules out such an
explanation. Rats on a high protein diet evidently become adapted very rapidly to
the diet given as can be seen from the complement levels and all other reactions.
At the end of the long-term experiment there was no difference, excepting only
weight, from the medium protein group. Changed reactivity after short-term admin-
istration of the diet may be explained by the animal adapting itself to the stress
of the unusual composition of the diet.This is evidently connected with ready usable
protein reserves depending on an optimal protein concentration in the diet. Similar
results were obtained by Hruza (1955) who studied the breakdown of liver proteins
after the short and long-term administration of diets containing high or low con-
centrations of proteins and also Lat (1955) who studied higher nervous activity in
rats fed a high protein diet for long periods.
During the long-term experiment the became differentiated. Animals on the high and
medium protein diets remained normal in appearance; this was not the case with
animals on the low protein diet. Their fur become sparse and in places was completely
absent. They rapidly succumbed to spontaneous infections.We are probably justified
in assuming (as more than one third of the animals died) that those that survived
were more resistant and became better adapted to dietary conditions. These
individuals, although the level of their total serum proteins was considerably decreased,
reacted in the same way to infection as animals from the other two groups. Normal
specific antibody formation in rats fed on a low protein diet for long periods may be
compared with the results of Bieler, Fcher and Spies (1947) and Balch (1950).
In conclusion it is necessary to point out that differences in resistance between the
three groups were not large and that often statistical evaluation is necessary to
demonstrate their significance. On the other hand differences between immunised and
non-immunised rats were immense both as far as bacteraemia and lethal doses are
concerned. This difference cannot be bridged by dietary means.
Summary
1'he short-term administration of a high medium and low protein diet gave rise
only to immunological differences within the two basic groups of immunised and
non-immunised animals.
After 8 months on those diets no differences in specific antibody formation, and
natural and acquired resistance to Salm. paraty phi B could be observed. llifferences
obtained in short-terra experiments disappeared in the long-term experiment. The
diets remained w~ithoat effect on the basic differences between immunised and non-
immunised rats in both experiments.
In the short-term experiment rats fed a low protein diet had a significantly decreased
complement level, agglutinating antibody titre and decreased acquired and natural
resistance to Sahn. paratyphi B infection in comparison with rats on an optimum,
medium protein diet.
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After 4 months on the low protein diet the amount of complement was decreased
in comparison with the medium and high protein diet groups.
In the short-term experiment when rats fed on a high protein diet are compared
with rats on the medium protein diet the titre of agglutinating antibodies of the form-
er after immunisation is significantly decreased but natural and acquired resistance
to infection is not changed.
Specific agglutinin formation is optimal on the medium protein diet which is also
optimal for growth and corresponds to the so-called protein optimum.
In the low protein group there was decreased survival due to spontaneous infections
so that there was a natural selection of more resistant individuals.
Statistical evaluation was carried out by F. Zitek, Mathematical Inst. of the Czechoslovak Academy
of Sciences. With the technical assistance of B. Hofmanov~ and D. Johanovska.
B a 1 c h, H. H.: Relation of Nutritional Deficiency in Man to AntibodyI'roduction. J. Immunol.
64 :397, 1950.
Berry, L. J., Davis, J., Spies, T. D.: The Relationship between Diet and the
Mechanism for Defense against Bacterial Infections in Rats. J. Lab. Clin. bled. 30:684,
1945.
B i e 1 e r, M. M., E c h e r, E. E., Spies, T. D.: Serum Proteins in Hypoproteinemia
Due to Nutritional Deficiency. J. Lab. Clin. Med. 32:130, 1947.
Cannon, P. R.: Antibodies and the Protein Reserves. J. Immunol. 44:107, 1942.
Cannon, P. R., Chase, W. E., W i s s 1 e r, R. W.: The Rel?~tionship of the Protein
Reserves to Antibody Production. I. The Effects of a Low Protein Diet and of Plasmaphoresis
Upon the Formation of Agglutinins. I. Immunol. 47:133, 1943.
Cannon, P. R., Wissler, R. W., Woolridge, R. L., Bendit, E. P.: 'Pt-e
Relationship of Protein Deficiency to Surgical Infection. Am. Surg. 120:514, 1944.
Cannon, P. R.: The Relationship of Protein Metabolism to Antibody Production and
Resistance to Infection. Advances in Protein Chemistry, New York 2, 1945.
F a l t o v a, E., P o u p a, O., S e r v f t, Z.: Vliv vzajemneho pom~ru glycidu a bilkovin
v potrave na ki?ebovou pohotovost u mysf. Fysiol. Ls. 4 : 10, 1955.
F o r n i, P. V.: Azoto protidico, accrescimento a resistenza antiinfettiva a antitossi difterica.
Medicina Sperimentale 23, 1952.
Guggenheim, K., B u e c h 1 e r, E.: Nutrition and Resistance to Infection. Bactericidal
Properties and Phagocytic Activity of Peritoneal Fluid of Rats in Various States of Nutritional
Deficiency. J. Immunol. 54 :349, 1946.
Guggenheim, K., B u e c h 1 e r, E.: The Effect of Quantitative and Qualitative Protein
on the Bactericidal Properties and Phagocytic Activity of the Peritoneal Fluid Rats. J. Immunol.
58:133, 1948.
H r ~ z a, Z.: O zasobach bilkovin v organismu. DisertaLni kandidatska prate, Praha 1955.
Krebs, E. G.: Depression of Gama Globulin in Hypoproteinemia Due to Malnutrition.
J. Lab. Clin. Med. 31:85, 1946.
L a t, J., F a 1 t o v a, E.: O ~innosti potravoveho centra. I. Regulate pi?ijimani vody a pevn~
fotravy. II. Regulate ppi;ijimani bilkovin, elektrolytu a vody. Fysiol. ~s. 3 : 132, 1954.
L a t, J., F a 1 t o v a, E.: Vliv vyiivy na vys""sf nervovou Linnost. I. Vliv ruzneho podilu
~ivoLisn$~ch bilkovin na vyssi nervovou Linnost krys. Fysiol. Ls. 4 : 171, 1955.
M e t c o f f, J., Favour, C. B., Stare, F. J.: Plasma Protein and Hemoglobin in
the Protein Deficient Rat. J. Clin. Investigation 24:82, 1945.
Metcoff, J., Darling, D. B., Scanlon, M. H., Stare, J. F.: Nutritional
Status and Infection Response. I. Electroforetic, Circulating Plasma Protein, Hematologic,
Hematopoetic and Immunologic Response to Salm. typhi murium. Infection in the Protein
Deficient Rat. J. Lab. Clin. Med. 33:1, 1948, 47-67.
P o u p a, O.: O nekterych u~incfch Fotravy nad jejich fysiologick$~m optimem. Referat na plx>-
narnim zasedani ~SAV, Praha, duben 1954.
Robertson, E. C., D o y 1 e, M. E.: Higher Resistance of Rats Fed Casein than Those
Fed Vegetable Protein. Prot. Soc. Exp. Biol. Med. 35:374, 1936--37.
Schneider, A. A.: Nutrition and Resistance to Infection. The Strategic Situation. Vitamin
and Hormones 4:35, 1936.
Schneider, H. A., Webster, L. T.: Nutrition of the Host and Natural Resistance
to Infection. II. The Effect of Diet on the Response of Several Genotypes of Mus musculus to
Sal. enteritidis Infection. J. Exp. Med. 81 :359, 1945.
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S t e r z 1, J.: Imunitni zmeny u dlouhodobe imunisovanj'ch zvi~at. Referat nu pracovni imuno-
logicke konferenci v Liblicich 1954.
t e r z 1, J.: Prukaz a biologick~ vlastnosti tkanovE~ho prekursoru serovvch protilatek. ~s. biu-
logic 4 :321, 1955.
S t e r z 1, J.: The Demonstration and Biological Properties of the Tissue Precursor of Serum
Antibodies, Fol, biol. (Praha) 1:193, 1955.
Wissler, R. W., Wollridge, H. L., Steffee, C. H., Cannon, P. R.:
The Relationship of the Protein Reserve of Protein Repletion Upon the Production of Antibody
in Hypoproteinemia Adult White Rats. J. Immunol. 1952, 267, 1946.
Wissler, R. W., W o o l r i d g e, R. L., S t e f f e e, C. H.: Influence of Amino Acid
Feeding Upon Antibody Production in Protein Depleted Rats. Proc. Soc. Exp. Biol. Med.
62:199, 1946.
Wissler, R. W., Woolridge, R. L., Steffee, C. H., Cannon, P. R.:
The Relationship of the Protein Reserves to Antibody Production. II. The Influence of Protein
Repletion Upon the Production of Antibody in Hypoproteinemic Adult White Rats. J. Immunol.
52 :267, 1946.
Watson, M.: Studies on the Influence of Diet on the Resistance to Infections. II. The Effect
of Various Diets on the Resistance of Mice to Bacterial Infection. J. Hyg. 37:420, 1937.
B e p Iu 1I JI o B a, H. A.: BJlnxxxe 6eJixoxo%I xeAocTaTO~IxocTH B nnulenoM pe.xlinle xa 6pygeJl-
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H HMMyxo.norllLl. MOCKBa 1954.
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 Approved For Release 2008/04/10 :CIA-RDP80T00246A002900500018-6
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FOLIA BIOLOGICA
Effect of Chlortetracycline on the Activity of u-an111ase.
M. BLRGER, J. ROKOS and Y. PROCHAJ.KA
Institute of Biology of the Czechoslovak Academy of Science, Department of Dlierobiology, Prah:~
On fermentation of chlortetracycline by Actinolnyces aureofaciens the fer-
mentation medium usually contains a source of starch (Van Dyck, De Sommer
1952) which splits up into lower derivatives. The extent of starch hydrolysis and the
possibility of using the sugars produced depend on the activity of amylolytic
enzymes.
It might be expected that with the accumulatioil of chlortetracycline in the fermen-
tation medium, particularly at higher concentrations of this antibiotic, the activit~?
of enzymes hydrolysing starch would be altered (Arora and Krishna Murti 1952).
Even though starchy raw materials (soya bean meal etc. ), contained in the fermen-
tation medium, probably have more functions than being the mere source of carboll.
the process must be conducted, for economic reasons, so as to make the best use of
the starch itself.
In order to study the effect of chlortetracycline on amylolytic enzymes, an enzyme
preparation was used from the mould Aspergillus oryzae: this is known, under the
experimental conditions in question, to hydrolyse starch exclusively by the action
of a-amylase (Burger and Beran 1956). Higher concentrations of chlortetracycline
were observed to have a strong inhibitory effect on this enzyme during the dextri-
nation of starch.
The purpose of the present work was to study the conditions under which inhibition
occurs and to try to find a method of preventing it, and, on the basis of the inform-
ation so obtained, to study the activity of amylase during the fermentation of
chlortetracycline by the strain of Actinomyces aureofaciens used commercially.
Analytical methods. The activity of a-amylase was determined using the author's modification of the
Wohlgemuth method (Belozersky and Proskuryakof 1951). Visual comparison of the starch iodine
complex with the standard solution was replaced by determination on a Pulfrich colorimeter. The red
filter S 6Fi, through which the iodine starch complex showed the highest absorption, proved to be the
best from among the set of standard filters available. The time taken for the dextrination of starch.
required for the calculation of the Wohlgemuth amylolytic units, was determined by the extrapolation
of the final transmission values. The activity of a-amylase is expressed both in units (Belozersky and
Prokuryakof 1951) and in percentage transmission in relation to the standard solution.
Chemicals used. Soluble starch p, a. (Lacherna), chlortetracycline with :i0 j~ biological acticit;y
(Lederle Lab.) and the other chemicals analytically pure.
Method. The enzyme preparation of A. oryzae, which under the given experimental conditions
(Burger and Beran 1956), causes dextrinization of starch exclusively by the action of a-amylase, was
used for the experiments. A suspension of this preparation in physiological saline was filtered and the
filtrate was dialysed for 24 hours at room temperature against a 400 tirnes larger volume of redistilled
water, changed three times. The amount of enzyme used was chosen so that dextrination was complete
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in about 45 minutes. The final concentration of starch was 1%. If not stated otherwise, the reaction
of the mixture was maintained at pH 5.6 by 0.1 M acetate buffer. Incubation took place at 30? C in
a water bath. The concentrations of antibiotic given are in relation to the final amounts of biologically
active chlortetracycline. The pH of the reaction solution was checked after each experiment by an
electron pH meter with a glees electrode.
The Effect of pH and Buffers on the Inhibition of Starch Dextrination
It was found that higher concentrations of chlortetracycline have an inhibiting
effect on the activity of a-amylase of the mould A. oryzae. The concentration of
chlortetracycline at which inhibition appears varies between 8 X 10-4 M and
1.2 x 10-3M (fig. 1-3).
Inhibition depends on the kind of buffer used and on the pH of the solution.
In an acetate buffer at pH 6.0 (fig. 2), chlortetracycline causes inhibition at
concentrations higher than 1.2 X 10-3 M. In a phosphate buffer of the same pH,
chlortetracycline causes inhibition at a concentration as low as 8 X 10-* M.
In a phosphate buffer at pH 7.0 and with the same concentration of antibiotic,
inhibition is greater (fig. 1 and 3).
Fig. 1. Effect of Concentrations of Chlortetra-
cycline on Inhibition of A. oryzae a-amylase in
a Phosphate Buffer of pH 6.0. x: time in mina.,
y: transmission in %. pH of solution 6.0, buff-
ered by phosphate at final concentration of
0.01 M. I: control, II: 400 fig., III: 600?g., IV:
800?g. and 1000 fig. chlortetracycline in 1 ml.
Fig. 2. Effect of Concentrations of Chlortetra-
cycline on Inhibition of A. oryzae a-amylase in
an Acetate Buffer of pH 6.0. x: time in mine.,
~: transmission in %, pH of solution 6.0, buff-
ered by acetate at final concentration of 0.1 M.
I: control and 400 Hag., II: 600 ?g., III: 800 ~~g.,
IV: 1000?g. chlortetracycline in 1 ml.
The inhibiting effect of chlortetracycline on starch dextrination is present in
acetate buffer from pH 4.8 upwards (fig. 4).
The In/luence of Ca `+ on the Inhibitory Effect of Chlortetracycline
It is well-known that Ca-f-+ acts as a stabiliser for a-amylases. We have proved,
however, that under our experimental conditions, the inhibition of a-amylase is not
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caused by the removal of Ca+ from the solution by chlortetracycline. Even a large
excess of Ca++ (tab. 1) did not cause any substantial changes in the inhibiting
effect of chlortetracycline. The results and the fact that a dialysed enzyme solution
was used in all experiments, prove that the inhibitory effect of chlortetracycline is
not caused by the removal of a low molecular stabiliser.
t i ~ J
.?0 60 90
Fig. 3. Effect of Concentrations of Chlortetra-
cycline on Inhibition of A. oryzae a-amylase in
a Phosphate Buffer of pH 7.0. x: time in mins.,
y: transmission in %, pH of solution 7.0, buff-
ered by phosphate at final concentration of
0.01 M. I: control, II: 400 ,rrg., III: 600 ; ~g.,
800 dig. and 1000 pg, chlortetracycline in 1 ml.
Fig. 4. Effect of pH on Inhibition of A. oryzao
x-amylase by Chlortetracycline. x: pH, y:
inhibition of A. oryzae a-amylase by chlortetra-
cycline. Buffered by acetate at final concentra-
tion of 0.1 M. Final concentration of chlortetra-
cycline 2 x 10-3M.
The Effect of some Organic Acids on the Inhibitory Effect of Chlortetracycline
Previous experiments had already shown (fig. 1 and 2) that the inhibition of
a-amylase, caused by chlortetracycline, depends on the kind of anions present. If the
anions of some organic acids; e. g. of citric or oxalic acid in concentrations of
X 10_x M are present, inhibition disappears completely. The anions of phthalic,
benzoic, fumaric and tartaric acids partially reduced inhibition; lactic and propionic
Table 1. Effect of Ca+~ on Inhibition of a-amylase by Chlortetracycline buffered by acetate, pH 5.6,
at final concentration O.l M
Experiment
Final Concentration
a-amylase
o.
units
of Chlortetracycline of CaC12
I ~
1.8 x 10-a M
LS x l0-~ M 0.84 ~I
2
1.8 x 10-3 M
(i x 10-3 M 0.74 ~~
3
1.8 x 10-3 M
- 0,45
4
-
L8 ;: 10_2 M 3.30
G
-
G ;: LO-'' M 3.50
6
-
- ~ 3.50
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Table 2. Effect of some Organic Acids on Inhibition of a-amylase by Chlortetracycline
buffered by acetate pH 5.6, final concentration 0.1 M. Final concentration of sodium salts of acids
2 x 10_2 M, of chlortetracycline 2 x 10_3 M
a-amylase units
Addition of
Sodium salt of added acid
__
Chlortetra-
Chlortetra-
0 I
Acid
I
cycline
cycline and acid
Oxalic
3.79
3.83
0.28
3.68
Citric
3.82
3.69
0.25
3.28
Phthalic
3.83
3.83
0.26
2.71
Fumaric
3.83
3.83
0.28
1.54
Benzoic
3.83
3.83
0.26
1.47
Tartaric
3.79
3.67
0.28
1.44
Propionic
3.83
3.75
0.23
0.27
Lactic
3.83
3.83
0.23
0.23
acids in acetate buffer had no effect whatsoever on inhibition caused by chlortetra-
cycline (tab. 2). These findings provided a starting point for resolving other problems,
particularly as to whether inhibition of the activity of a-amylase by chlortetra-
cycline is reversible or irreversible.
The addition of citrate (acetate buffer) or acetate (phosphate buffer) to a reaction
mixture in which a-amylase has previously been inhibited by chlortetracycline,
removes the inhibition (fig. 5 and 6). The rate of starch dextrination after the
addition of these acids is the same as when chlortetracycline is not present. The
0 1.5 3p 45 ~i
Fig. 5. Effect of Subsequent Addition of Citrate
on A. oryzae a-amylase Inhibited by Chlortetra-
cycline. x: time in mina., y: transmission in %.
pH of solution 6.0, buffered by acetate at final
concentration of 0.1 M. I: control, II: 1000 ~~g.
chlortetracycline in 1 ml. in the 45th minute.
1 ml. of Na-citrate (final concentration 2 X
v 10_Q M), has been added. III: 1000 Ng. chlor-
tetracycline in 1 ml., in the 45th minute, 1 ml.
of HEO has been added.
Fig. 6: Effect of Subsequent Addition of Acetate
on A. oryzae a-amylase Inhibited by Chlortetra-
cycline. x: time in mine., y :transmission in ?%,
pH of solution 6.0, buffered by phosphate at
final concentration of 0.01 M. I: control, II:
600 ?g. chlortetracycline in 1 ml., in 45th min.
1 ml. Na-acetate (final concentration 2 x 10-1 M)
has been added, III: 600 ,ug. chlortetracycline in
1 ml. in 45th min. 1 ml. of H=O has been added.
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removal of inhibition is thus complete. The results given here prove that inhibition
of a-amylase by chlortetracycline is reversible.
In addition to studies on the bacteriostatic or bactericidal effect of antibiotics.
a number of papers have been published dealing with the question of the action of
antibiotics on separate enzyme systems both in vivo and in vitro (Agarwala et
al. 195?, Arora et al. 1954, 1955a, b, Brody et al. 1954, Ghatak et al. 1953, Iyer et
al. 1953, Jacobson et al. 1954, Loomis 1950, Saz et al. 1954, Zimmerman et al. 1953).
It is a characteristic feature of these papers that far higher concentrations of antibio-
tics were used than those at ~~hich their bacteriostatic and bactericidal properties
are already displayed. This very fact would suggest that in these cases the effect of
antibiotics ott the enzyme system is non-specific and it is doubtful whether the
results obtained can be used to explain changes in enzymatic processes at concentra-
tions of the antibiotic which affect the multiplication of the microorganisms. We also
used high concentrations of chlortetracycline when studying its effect on the activity
of a-amylase in starch dextrination. The concentrations used, however, are of
importance in the fermentation of Actinomyces aureofaciens, where the high con-
centration of the antibiotic can affect some enzyme systems.
Our experiments prove that higher concentrations of chlortetracycline inhibit
dextrination by a-amylase of A. oryzae. It is important that this inhibition can
easily be removed by some organic acids, which alone, however, do not affect the
activity of the enzyme in question. This provides the possibility of studying how
a-amylase of Actinomyces aureofaciens is affected during fermentation with the
production of chlortetracycline and, in case of inhibition, of measuring the a-amylase
content.
Van IVleter and Oleson (1951) assume that chlortetracycline inhibits some reactions
in Kreb's cycle, since citric acid removed inhibition by chlortetracycline in studies
on the respiration of rat liver homogenates. The fact that citric and other acids
removed the inhibitory effect of chlortetracycline on the amylolytic enzyme system
in our experiments too, suggests that chlortetracycline may affect other systems
connected with liver respiration.
In some cases lower concentrations of antibiotics stimulate enzyme activity while
higher concentrations inhibit it (Smith et al. 1949). This may also apply for the
action of chlortetracycline on a-amylase. Arora et al. (1952) found that with lower
concentrations than those used in our experiments there is activation of the amylo-
lytic systems of malt and moulds. It must be stressed, however, that these authors
observed the activity of the amylolytic system from the point of view of increasing
the reduction rate, and did not exclude the effect of other enzymes, particularly
maltase.
~.~~ummary
The inhibitory effect of chlortetracycline in concentartions of 8 x 10_4 M and
higher on the dextrination activity of a-amylase of the mould Aspergillus oryzae was
demonstrated and the effect of pH, Cam ~ and some organic acids on this inhibition
was studied.
Inhibition of a-amylase by chlortetracycline can be removed by citrate, oxalate
and other anions of organic acids. The inhibition of a-amylase is reversible.
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Agarvala, S. C., Krishna, Murti, C. R? Shrivastava, b. L.: Studies
on Enzyme Inhibition in Relation to Drug Action. I. Effect of Certain Antibiotics on Ureasl~.
J. Sci. Industr. Res. 11B :165, 1952.
.1 r o r a, K. L., Krishna M u r t i, C. R.: Studies on Enzyme Inhibition in Relation to
Drug Action. III. Action of Certain Antibiotics on Amylases. J. Sci. Industr. Res. 11B :383,
195`l.
A r o r a, K. L., Ii r i s h n a M u r t i, C. R.: Enzyme Inhibition Studies in Relation to
Drug Action. VI. Action of Certain Antibacterial Agents on the Succinic Oxidase System.
J. Sci. Industr. Res. 13A :482, 1954.
A r o r a, K. L., Krishna b1 u r t i, G. R.: Studies on Enzyme Inhibition in Relation to
Drug Action: VII. Action of Certain Antibacterial Agents on Tryptophanasa. J. Sci. Industr.
Res. 14C : 6, 1955a.
A r o r a, K. L., Krishna M u r t i, C. R.: Enzyme Inhibition Studies in Relation to
Drug Action: VIII. Action of Certain Antibacterial Agents on the Tricarboxylic Acid Cyclo
of Vibrio Cholerae. J. Sci. Industr. Res. 14C : 66, 1955b.
Brody, T. M., H u r s i t z, R., Bain, J. A.: Magnesium and the Effect of the Tetra-
cycline Antibiotics on Oxidative Processes in Mitochondria. Antibiot. Chemother. 4:864,
1954.
Burger, M., B e r a n, K.: O mechanismu u~inku maltasy plisn5 Aspergillus niger, I. Vliv
teploty na aktivaci hydrolysyskrobu plisnovymi enzymatlckymi preparaty. Chem. linty
50 :133, 1956.
Van Dyck, P., D e Sommer, P.: Production and Extraction Methods of Aureomycin.
Antibiot. Chemother. 2 : 184, 1952.
C h a t a k, S., Krishna M u r t i, C. R.: Enzyme Inhibition Studies in Relation to Drug
Action: IV. Action of Certain Antibiotics on Alkaline Phosphatase. J. Sci. Industr. Res. 12
12B :160, 1953.
I y e r, S. N., A r o r a, Ik. L., Krishna bI u r t i, C. R.: Studies on Enzyme Inhibi-
tion in Relation to Drug Action: V. Effect of Certain Antibiotics on Liver Arginase. J. Sci.
Industr. Res. 12B :536, 1953.
Jacobson, K. P., D e o d a t a d e A z e v e d o, M.: Action of Antibiotics on a Pepti-
dase and on Urease. Compt. Rend. Soc. Biol. 148:199, 1954.
Loomis, W. F.: On the Mechanism of Action of Aureomycin. Science 111:474, 1950.
Van Meter, J. C., O 1 e s o n, J. J.: Effect of Aureomycin on the Respiration of Normal
Rat Liver Homogenates. Science 113:273, 1951.
S a z, A. K., S 1 i e, R. B.: Reversal of Aureomycin Inhibition of Bacterial Cell-free Nitro
Reductase by Manganese. J. Biol. Chem. 210:407, 1954.
Smith, G. N., W o r r e 1, C. S., Swanson, A. L.: Inhibition of Bacterial Esterases
by Chloramphenicol (Chloromycetin). J. Bact. 58:803, 1949,
7, i m m e r m a n n, H. J., H u m o l l e r, F. L.: Effect of Aureomycin on Choline Oaidasr
and Other Enzyme Systems of Rat Liver. Am. J. Physiol. 175:468, 1953.
F e s o a e p c x n ~, A. H., H p o c x y p a x o B, H, H.: HpaxTlluecxoe pyxosu;[cTSO no fiwo-
xHMxx pacTexn~. Moclcsa 1951.
BJII~IRHLIO XJIOpTeTjJal[I3I{JIYIHa Ha a1=fTI~IBHOCTb a-aMYIJIa3bI
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I~paTxHe coo6u~eHi~x Brief Reports Kurze Mitteilungen
Transmissible Lysis of Cells of Escherichia coli Induced
by X-ray Radiation
F. HER~IK
Institute of Biophysics, Czechoslovak Academe of Science, Brno
Received April 27, 1.956
Bacteria of Escherichia coli which are given suitable doses of supersonic treatment,
lyre, and are at the same time converted Tonto a quantity of uniform globules meas-
uring 200-300 1~ in diameter (Hrade~na 1956a). An ultrafiltrate of cells lysed in
this way induces lysis in healthy cells of the same strain. This lysis can be trans-
mitted (Hrade~na 1956b).
The present work aimed at ascertaining whether X-ray radiation can induce
similar lysis and whether this also can be transmitted. To date, over 68 experiments
have been carried out and the preliminary results are given in the present report.
A Chaoul tube was used to carry out the irradiation (56 kV, 3 mA, 0.15 mm Cu,
dose-rate 111 r . m-1). The radiation dose was measured by the compensation
method, using aTaylor-Stoneburner chamber (Her~ik 1948). Three strains of Esche-
richia coli were taken for irradiation, most experiments being carried out with the
strain E. coli B, which was obtained from the Institute of Biophysics of Geneva
University through the kindness of Dr. Kellenberger. This strains is not lysogenic.
Cultures of varying ages (1- 24 hours, but most frequently three hours old) were
irradiated in test-tubes under strictly sterile conditions. A suspension of bacteria
with a concentration of 10',(ml. broth was used. The density of the bacteria was
measured turbidimetrically. After irradiation, the bacteria were filtered through
a collodion filter with pores averaging 620 m,u and 5 ml. of the filtrate was added
to a 24-hour-old suspension of non-irradiated bacteria in broth. Non-irradiated,
filtered bacteria, 5 ml. of which was also added to a 24-hour-old suspension of non-
irradiated bacteria, acted as controls. In both cases the concentration of the bacteria
was about 1081m1.
Of the total number of 68 experiments, '~'? were positive, indicating that after
the addition of the filtrate complete clearing of the culture had occurred, either
during the first passage or in one of the subsequent passages. A filtrate from the
cleared culture again contained the lytic factor. Up to nine passages were made.
Titration carried out in the third passage showed that the lytic factor was present
in the titre of 105-10%. A filtrate from the control, non-irradiated bacteria did not
induce lysis. In the electron Inicroscope preparations from the lysate showed lysed
cells with typical uniform globules with a diameter of about 300 1~. The experiments
made so far indicate that in order to induce lysis by X-ray irradiation, a definite
optimal dose is needed. Measured in air, this ranges from 75-300 r. It is quite simple
to calculate that in a bacterium with a volume of 0,5 ~~~, the dose of 300 r. produces
about 600 ionisations. An average of 4.10-3 ionisations falls to one globule, i. e.
every 250th globule is ionized. The frequency of the whole phenomenon varies and
it evidently depends on the physiological state of the bacterium, on the optimal dose
and on other factors which are still not known.
In summing up it may be said that X-ray irradiation induces lysis in non-lyso-
genic bacteria of E. coli B and that this lysis can be transmitted.
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H e r c i k, I~'.: Analyses vlnoveho iSinitele s hlediska kvaxitovc biologickeho. dpi.-~5~ 1Lk. fak. MCA, l2,
cia. 3. 1943.
H e r c i k, F.: Problem bakteriof:iga. Praha 19~i3.
H r a d ?c n ~4., Z.: Rozpad bal~terii v uniformni globul3~ pod vlivom ultrazvuku. ~'s. biologie 5:117,
1956a.
H r a d e c n a, Z.: Laaa hykterii Escherichia e~oli vwolana filtratem ozvubeny~h bakterii. ~a. biologiri
+~ : ~41? ]956b.
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Ync. 1. AnTOTpaxcnnaxTaT vepea 14 Axei3 nocne xepecaRxx. YRe~nn~+exxe a 4U paa.
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(IIapa~xxoavie cpess~, oxpacxa rehtaTOFSCxnnx-soa~rxont,)
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