Psychology

Bovine neonatal immunology

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The majority of early, in utero immune development occurs independent of antigen exposure. Only later during development can a fetus respond to antigens, and even then the response depends on the stage of fetal development and the nature of the
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  BOVINE NEONATAL IMMUNOLOGY George M. Barrington, DVM, PhD, Dipl. ACVIM,* and Steven M. Parish, DVM, Dipl. ACVIM †* Assistant Professor, Department of Veterinar Clini!al S!ien!es, College of Veterinar Medi!ine, "ashington State #niversit, P$llman, "ashington %%&'(† Professor, Department of Veterinar Clini!al S!ien!es, College of Veterinar Medi!ine, "ashington State #niversit, P$llman, "ashington %%&'(Dr. Barrington )ill serve as !orresponding a$thor Phone +%-+-/ 0a1 +%-+- geo23vetmed.)s$.ed$  SYNOPSIS: 4arl fetal imm$ne development o!!$rs independent of antigen e1pos$re )hereas later development depends on e1pos$re to spe!ifi! antigens. Altho$gh neonates are imm$no-!ompetent at 2irth the are !learl imm$no-na5ve and dependent on  passivel a!6$ired maternal imm$noglo2$lins, imm$ne !ells and other s$2stan!es from !olostr$m for prote!tion. 7eonates that s$ffer fail$re of passive transfer of maternal imm$noglo2$lins ma 2e at in!reased ris8 for disease, ho)ever man other fa!tors intera!t in !on9$n!tion )ith the level of passivel a!6$ired imm$noglo2$lin to determine the o!!$rren!e of disease. OVERVIEW OF IMMUNOLOGIC DEVELOPMENT IN UTERO As the fet$s develops in-$tero, there is a progressive development of vario$s non-imm$ne and imm$ne defense me!hanisms. :hese me!hanisms !an 2e !ategori;ed into those that are dependant on antigen re!ognition 2 anti2od and or lmpho!tes <spe!ifi!, a!6$ired= and those that o!!$r independent of s$!h re!ognition events <non-spe!ifi!, native=. Altho$gh spe!ifi! and non-spe!ifi! me!hanisms !an ea!h a!t independentl to promote host defenses, more often the a!t in !om2ination and therefore provide greater prote!tion than either sstem !an do alone. All of the vario$s !ells that  provide 2oth spe!ifi! and non-spe!ifi! defense me!hanisms srcinate from the same m$ltipotential hemopoieti! stem !ells.  7on-imm$ne defense me!hanisms in!l$de effe!ts s$!h as en;mes in se!retions, a!ids in the stoma!h, fatt a!ids in epitheli$m, and normal flora that !oloni;e m$!osal s$rfa!es on!e the neonate is 2orn. 7on-imm$ne defenses also in!l$de the !omplement >  sstem and phago!ti! !ells <2oth ne$trophils and ma!rophages= that differentiate from m$ltipotential stem !ells. :hese !ells li8el !ontri2$te onl minimal prote!tion in earl fetal life sin!e the remain at their derivation sites $ntil 2eing released into the 2lood at appro1imatel & das gestation <(=. Indeed, ne$trophils !ontri2$te little to fetal inflammator pro!esses and fetal ma!rophage f$n!tion is less than that of ad$lts )ith regard to assisting the imm$ne response, phago!tosis and gran$loma formation. B late gestation, fetal ne$trophils are !apa2le of phago!ti! a!tivit, ho)ever their 2a!teri!idal a!tivit ma 2e de!reased. 7ear 2irth, the phago!ti! and 2a!teri!idal !apa!it of ne$trophils de!lines as a res$lt of in!reased fetal !ortisol levels <'>=. Ba!teri!idal a!tivitin the ser$m of the 2ovine fet$s is present 2 /+ das gestation and meas$ra2le hemolti!!omplement a!tivit has 2een reported at appro1imatel % das gestation <(+=. ?o)ever,thro$gho$t gestation 2ovine fetal !omplement levels are appro1imatel half that fo$nd in ad$lt !attle. In s$mmar, non-imm$ne defense me!hanisms in!rease in their effe!tiveness thro$gho$t gestation and tho$gh the are f$n!tional 2 2irth, the !an 2e s$ppressed 2 stress, maln$trition, lo) level infe!tions, or e1pos$re to to1ins. A!6$ired imm$ne defenses !onsist of anti2od, memor lmpho!tes, and effe!tor !ells. As lmpho!tes develop from stem !ells, the are initiall released into the 2lood then later move to spe!ifi! lo!ations to $ndergo f$rther differentiation. :-lmpho!tes mat$re in the thm$s )hereas B-lmpho!tes $ndergo f$rther mat$ration inthe 2one marro) and Peer@s pat!hes. D$ring the first trimester of gestation, : and B-lmpho!tes move from primar lmphoid organs to pop$late the lmph nodes, spleen and m$!osal lmphoid tiss$es. All this a!tivit o!!$rs independent of antigen e1pos$re and stim$lation.   If a fet$s is e1posed to a foreign antigen, )hether or not an imm$nologi!al rea!tion o!!$rs )ill depend on )hat stage of development the fet$s is in, as )ell as the nat$re of the parti!$lar antigen. 0or e1ample, at &> das gestation the 2ovine fet$s !an develop anti2odies to parainfl$en;a  vir$s 2$t not other vir$ses or 2a!teria <(=. B &% das gestation the fet$s !an prod$!e anti2od against 2ovine vir$s diarrhea vir$s, and at  2irth !an prod$!e anti2odies against  Brucella abortus . As fetal development !ontin$es thro$gho$t gestation, an in!reasing n$m2er of antigens !an res$lt in ind$!tion of an imm$ne response. B the time a !alf is 2orn it !an respond to a )ide variet of antigens,  2$t still not as man as )hen it is f$ll mat$re.:here are at least  distin!t !onse6$en!es to fetal infe!tions. 0irst, death of the fet$s !an o!!$r if the immat$re or inade6$ate defense me!hanisms allo) infe!ting organisms to repli!ate freel and destro tiss$es. 0atal infe!tions $s$all o!!$r d$ring earl gestation, )hen the fetal imm$ne sstem !annot mo$nt an prote!tive response. Se!ond, fetal infe!tion !an res$lt in persistentl infe!ted animals that remain infe!ted intoneonatal or ad$lt life. Spe!ifi! vir$ses !an ind$!e imm$nologi! toleran!e or hpo-responsiveness res$lting in little or no anti2od prod$!tion. 41amples of s$!h infe!tions in!l$de 2order disease of sheep and 2ovine vir$s diarrhea infe!tion of !attle. A third tpe of rea!tion !an o!!$r )hen fetal lmpho!tes have differentiated to the point )here the !an re!ogni;e prote!tive antigens of the invading organism. In the event the fet$s !an  2oth re!ogni;e and rea!t to s$!h antigens, it ma 2e s$!!essf$l in ridding itself of infe!tion. :he o$t!ome of this form of fetal infe!tion is dependent on similar fa!tors that determine the fate of infe!tions in ad$lt animals. (  IMMUNE RESPONSE OF THE NEWBORN #pon leaving the sterile $terine environment, neonates are e1posed to environmental !onditions that are laden )ith mi!roorganisms. :ho$gh the are !apa2le of mo$nting an imm$ne response, neonates are 2est !hara!teri;ed as 2eing imm$no-na5ve. :his ina2ilit to initiate a s$!!essf$l imm$ne response is d$e the immat$rit of prote!tiveme!hanisms as )ell as the time dela in the initiation and prod$!tion of me!hanisms ne!essar for the generation of h$moral and !ell mediated imm$nit. Indeed, the initial response that is mo$nted is tpi!all a primar response )ith a prolonged lag period and lo) !on!entrations of imm$noglo2$lins 2eing prod$!ed. :herefore, $nless ade6$ate maternal imm$nologi!al assistan!e is provided, neonates have an in!reased li8elihood of s$!!$m2ing to infe!tions that are inno!$o$s to ad$lt animals. :he imm$nologi!al assistan!e that neonates re!eive is via imm$noglo2$lins and other fa!tors present in !olostr$m. :his topi! )ill 2e dis!$ssed in greater detail in follo)ing se!tions. At 2irth, 2oth primar and se!ondar lmphoid organs are pop$lated 2 !ells that have developed independent of antigeni! stim$lation and the n$m2er of !ir!$lating B-lmpho!tes is appro1imatel  of that fo$nd in an ad$lt. In !alves, B-lmpho!te n$m2ers rea!h ad$lt levels after appro1imatel > das post part$m <+'=. In general, the imm$noglo2$lins prod$!ed 2 these !ells appear in the 2lood a fe) das after 2irth. 0or e1ample, 2et)een ' h and  )8s of age, endogeno$s prod$!tion of IgG &  is estimated to  2e appro1imatel & gram of IgG& per da <&=. Similar to that des!ri2ed in $tero, !alves )ill respond to spe!ifi! antigens at different times earl in life. "hereas some antigens )ill eli!it an anti2od response in the first das of life, others )ill re6$ire several )ee8s +
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