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Folia Medica Indonesiana Vol. 44 No. 2 April – Juni 2008 :

Review Article:

PROTEIN CALORIE MALNUTRITION AND IMMUNE RESPONSE IN CHILDREN

Roedi Irawan

Department of !ild "ealt!

Airlan##a $ni%ersit& 'c!ool of MedicineDr 'oetomo (eac!in# "ospital) 'ura*a&a

ABSTRACT

The fundamental relationship between malnutrition and immunity was initially described as a thymolymphatic

deficiency caused by protein calorie malnutrition (PCM). The selective sensitivity of the thymus to nutritional injury is

specifically important in the formative phases of the fetal and neonatal immune system. Recent studies suggest that

prenatal nutrition and growth during the first of life may predict thymic function in adolescence. Related studies have

shown that prenatal inc deficiency is associated with decreased immune function in later life. The prenatal inc

deficiency is generally accepted that age related in immune response appear to be seen from programmed involution

of the thymus. Thymic involution and induction of thymulin secretion from human thymic epithelial cells have

obtained with inc treatment! suggesting that specific nutrients may act as regulatory elements by modulating cellular programs. The potential significance of early nutrition for adaptive immune response in general is also indicated by

studies of mucosal immune response to antigens! which have shown that e"perimental priming at birth ensured both a

stronger and a more lasting immune response toward potential pathogens. Malnutrition has an adverse impact on

immunological functions and can serve to suppress cell#mediated! humoral! and secretory immune competence.

$utritional immunodeficiencies in human beings appear to respond well to dietary therapy. Micronutrients! trace

elements! and vitamins have important regulatory effects on adaptive immune cell function.

Keywords% malnutrition! immune response

Corresondence : +oedi Ira,an) Department of !ild "ealt!) Airlan##a $ni%ersit& 'c!ool of Medicine) Dr 'oetomo(eac!in# "ospital) Jl -rof Dr Moestopo – 8) 'ura*a&a) p!one 2/1/013) mo*ile 0818411) email:roedi5dr6&a!oo.com

INTRODUCTION

-M 7protein calorie malnutrition is defined asmarasmus) c!aracteri9ed *& a c!ronic ,astin#condition) or ,as!ioror or com*ined as marasmic

,as!ioror. -M ma& in%ol%e ener#& deficienc&) protein deficienc&) %itamin and mineral depri%ation. If prolon#ed) -M produces ,astin# and stuntin#7;eisel 200. Malnutrition !as an ad%erse impact onimmunolo#ical functions and can ser%e to suppresscell/mediated) !umoral) and secretor& immune

competence. Nutritional immunodeficiencies in

!uman *ein#s appear to respond ,ell to dietar&t!erap&) ,it! impro%ement in some functions *ecomin# e%ident ,it!in a fe, da&s of initiatin# arefeedin# pro#ram 7unnin#!am et al. 133. "ostdefense re<uires ener#& e=penditure) and t!is rapidl&

*ecomes compromised in t!e malnouris!ed or c!ronicall& infected !ost 7'c!midt 133. urrentin%esti#ations also descri*e t!e t!&mus as t!e *arometer of malnutrition) are identif&in# !o,specific nutrient deficiencies suc! as 9inc correlate,it! clinical malnutrition and impaired t!&mic

function) and furt!ermore see to no, !o, critical

molecular processes ma& *e affected 7Fraer et al.2000.

-renatal undernutrition reflected in intrauterine#ro,t! retardation leads to reduced t!&mopoietin

production. (!e stud& reported t!at adolescents ,!o,ere small for #estational a#e 7'>A at *irt! !adlo,er t!&mopoietin le%els ,!en compared ,it!control adolescents ,!o ,ere appropriate for #estational a#e 7A>A at *irt!. In *ot! #roups)t!&mopoietin le%el durin# adolescence correlated ,it!

#ro,t! in len#t! durin# t!e first &ear of life 7McDade

et al. 2001.

MALNUTRITION ON IMMUNE RESPONSE

AND IN!ECTION

(!e importance of !ost #enetic pol&morp!ism !asalread& *een reported for infections suc! astu*erculosis) ,!ic! is malnutrition an important ris factor. "ost defense re<uires ener#& e=penditure) andt!is rapidl& *ecomes compromised in t!e

malnouris!ed or c!ronicall& infected !ost. -at!o#ens



-rotein alorie Malnutrition and Immune +esponse in !ildren 7+oedi Ira,an

suc! as parasitic infections or %iruses ma& easil&

compromise t!ese resources) and if malnutrition is present) t!e o%erall de%elopment and e=pression of immune response are si#nificantl& impaired. A critical!&pot!esis is t!at conditionall& essential nutrient

re<uirements ma& *e associated ,it! e& sta#es of de%elopment 7;eisel 2000.

urrent t!inin# a*out t!e fundamental nature of immune response places ma?or emp!asis on t!emicroen%ironment. Innate immune cells suc! asnatural iller 7N@ cells and N@ ( cells) monoc&tes)and dendritic cells influence t!e pattern of c&toine

produced *& t!e adapti%e immune s&stem) in part *&directl& secretin# t!eir c&toine products into t!emicroen%ironment. Infections tri##er initiation of t!eacute/p!ase response) affectin# nutrient meta*olismand modulatin# c&toine pat!,a&s 7>alla#!er Dal&

200.

(!e mec!anisms t!rou#! ,!ic! nutrients affectimmune functions fre<uentl& include modulation of t!e c&toine response and are reflected in c!an#es int!e o%erall c&toine pattern. &toines are producedin response to tri##erin# e%ents suc! as infection and

cancer *ut are also induced in response a ,ide ran#eof stress si#nals) includin# nutrient depri%ation.&toine response is essential for !ost defense. If uncontrolled) it can also lead to t!e e=treme state of septic s!oc) causin# loss of lean tissue and *od& fat.(o a lesser de#ree) some of t!e o*ser%ed effects of

malnutrition ma& also in%ol%e concurrent su*clinicaland #enerali9ed infectious processes) particularl& fromopportunistic pat!o#ens actin# t!rou#! mediatorscommon to t!e acute/p!ase response) as illustrated inFi#ure 1. B=amples include t!e effects of nutrientalteration on !ost immune response associated ,it!

!uman immunodeficienc& %irus 7"IV infection or parasitic infections 7;eisel 2000. Alt!ou#!malnutrition is often considered as mainl& in issue for underde%eloped countries) su*optimal nutrition isrelati%el& common in c!ildren t!rou#!out t!e ,orldand is a si#nificant cause of suscepti*ilit& to infection

pat!,a&s 7C9an et al. 1338.

HOST DE!ENSE IN PROTEIN CALORIE

MALNUTRITION "PCM#

-M distin#uis!ed *& edema and anemia. A mi=ture

of features of *ot! conditions and #radations of e=pression are fre<uentl& o*ser%ed amon#malnouris!ed c!ildren 7unnin#!am et al. 133.-M ma& in%ol%e ener#& deficienc&) proteindeficienc&) %itamin and mineral depri%ation. If prolon#ed) -M produces ,astin# and stuntin#. -M

encompasses a ran#e of protein ener#& deficienc&

states) from marasmus to marasmic ,as!ioror.

-rotein insufficienc& alone) ,it! or ,it!out infection)causes edema associated ,it! !epatome#al& fromfatt& infiltration of t!e li%er. (!e manifestation of clinical malnutrition are related to t&pe) se%erit&) and

duration of nutritional impairment and ma& *esu*clinical) re%ersi*le) or irre%ersi*le dependin# on

t!e a%aila*ilit& treatment) presence of ot!er diseasesor complicatin# disorders) and t!e de#ree of dama#e.A ,ide ran#e of effects is o*ser%ed t!at affect man&or#an s&stems and specific tissues) re<uirin#inte#rated clinical mana#ement accordin# to t!ese%erit& and features at presentation 7unnin#!am et

al. 2002.

Fi#ure 1. Illustration of some of t!e e& interactionst!at lead to altered immune response in t!e

malnouris!ed !ost durin# infectiouse=posure. I E interleuin. ('F E tumor necrosis factor.

(!e effect of nutrient deficienc& on immune response

and !ost defense !as *een primaril& studied in -Mand in micronutrient deficiencies. $ndernutrition)especiall& -M) is clearl& associated ,it! increasedsuscepti*ilit& to infections and ,it! #reater mor*idit&from infections. "o,e%er) t!e pro=imate cause of

reduced !ost defense and increased mortalit& fromacute respirator& infections o*ser%ed in t!emalnouris!ed c!ild is often related to a com*ination of factors rat!er t!an to a sin#le factor 7in et al. 1338.

;ot! marasmus and ,as!ioror are c!aracteri9ed *&reduced antio=idant acti%it&) an important component

of !ost defense. (alti and collea#ues !a%e descri*edreduced red cell #lutat!ione) and increased lipid pero=idation in c!ildren ,it! marasmus) ,!ereas +eidand collea#ues o*ser%ed decreased er&t!roc&te#lutat!ione s&nt!esis in ,as!ioror. Alt!ou#! t!e *asis of edema in ,as!ioror is unclear) t!is is




pro*a*l& lined to increased le%els of inflammator&

c&toines) specificall& I/ and /reacti%e protein)and to t!e action of t!e solu*le receptors of tumor necrosis factor 7(NF 7Do!ert& et al. 1333.

-rimar& malnutrition is associated ,it! atrop!& of l&mp!oid or#ans and profound immune malfunction

leadin# to suscepti*ilit& to pat!o#ens) reacti%ation of %iral infections) and de%elopment of opportunisticinfections. (!e effect of malnutrition on (/cellmaturation and t!&mic function is particularl&important in c!ildren in ,!om t!e adapti%e immuneresponse is formin#. Malnutrition leads directl& to

t!&mic in%olution) re%ealin# t!e t!&mus #land as t!e *arometer of malnutrition in c!ildren. As su##ested *&studies comparin# A>A and '>A *a*ies) prenatalundernutrition ma& *e #enerall& lined ,it! t!&micfunction in adolescence. Nutritionall& caused t!&mic

in%olution is %er& similar to con#enial t!&mic aplasiain terms of effects on immune function and !ostdefense 7>rie*el et al. 200.

&mp!oc&te de%elopment and differentiation aredirectl& affected *& malnutrition as a conse<uence of t!&mic deficienc&. !en ( cells from c!ildren ,it!

se%ere -M ,ere compared ,it! t!ose from ,ell/nouris!ed c!ildren) immature differentiation ,asdirectl& associated ,it! t!&mic in%olution asmeasured *& ec!oradio#rap!&. Alt!ou#! re#ro,t! of t!e t!&mus is lon#er t!an restoration of normal *od&,ei#!t ,!en c!ildren ,ere fed) t!is could *e

si#nificantl& !astened *& t!e addition of 9incsupplementation. (!&mic in%olution can also occur secondar& to infections caused *& malnutrition *ecause t!e t!&mus is e=traordinaril& suscepti*le tostress depletion 7C9an et al. 1338.

B=perimental studies s!o, t!at t!e t!&mus isunusuall& %ulnera*le to pro#rammed cell deat!.'tudies in t!e #eneticall& ,asted mouse su##est t!att!e central a*normalit& ma& *e a !i#! or prematurerate of spontaneous apoptosis in t!e t!&moc&te population. -ossi*l& related effects !a%e *een

o*ser%ed in rats rendered ma#nesium deficient *& diet.

In t!ese studies) Malpuec!/;ru#ere and collea#uesfound acceleration of t!&mic in%olution and apoptosis.In t!ese studies) ma#nesium deficienc& causeden!anced inflammation and suscepti*ilit& to pero=idation in association ,it! increased apoptosis.

+ecent studies *& "offman/>oet9 reported t!at artifi/cial rearin# ,it!out maternal factors is associated ,it!reduced t!&mic cell num*er and ,ei#!t compared,it! maternal rearin# of rat pups. (!ese studiessu##est in%ol%ement of t!e !&pot!alamic/pituitar&/adrenal a=is in t!&mic !omeostasis 7McDade et al.

2001.

+eported immunolo#ic a*normalities in se%erel& mal/nouris!ed infants and c!ildren !a%e *een primaril&related to t!e cellular immune s&stem. +elati%el&fe,er c!an#es in o%erall immuno#lo*ulin le%els !a%e

*een found) alt!ou#! I#Al and I#A2 tend to *e !i#!er.+iimaru and collea#ues undertoo a s&stematic

e%aluation of l&mp!oc&te su*populations andimmuno#lo*ulins amon# normal c!ildren and c!ildren,it! ,as!ioror) marasmus) and marasmic,as!ioror. I#A and 4 ,ere !i#!er) ,!ereas andrelati%e ; cell percenta#e ,ere lo,er in t!e se%erel&malnouris!ed #roups 7Mc>ee McMurra& 200.

'erum le%els of immuno#lo*ulins do not predict spe/cific de no%o anti*od& response) and specific studiessu##est t!at malnutrition affects some immuno#ensmore t!an ot!ers. 'tuntin# appears to *e stron#l&

associated ,it! decreased I#> anti*od& response tomeasles. Decreased ) decreased (NF/G) and I/response to lipopol&sacc!aride stimulation in %itro arealso c!aracteristic of malnouris!ed c!ildren. -roteindepri%ation alone ma& cause reduced p!a#oc&ticacti%it& and impaired I/1 and I/ production) ,!ilesparin# monoc&te anti#en interaction 7Do!ert& et al.

1338. B=perimental studies in t!e rat !a%e su##estedt!at lo, dietar& protein affects t!e #ut immune s&stemat se%eral le%els) includin# mucosal I#A) secretor&component) t!e num*er of I#A/containin# cells) andt!e le%el of I#>. (!ese studies ,ere conducted in t!ea*sence of caloric restriction and could *e re%ersed *&

refeedin#. "o,e%er) t!e effects of a sin#le #rain dietsuc! as mai9e ma& also *e related to meta*olites of dietar& constituents rat!er t!an to nutrient a*sence.urrent t!inin# su##ests t!at t!e !i#! le%el of linoleic acid in mai9e in t!e a*sence of ot!er pol&unsaturated fatt& acids in t!e diet ma& cause

increased production of ->B2) leadin# to do,nre#ulation of (!1 c&toine production 7Mc>ee McMurra& 200.

'ome of t!e effects of -M mi#!t in%ol%e endocrineinteraction ,it! t!e immune s&stem. Ham*oni and col/

lea#ues o*ser%ed !i#! *asal #ro,t! !ormone 7>"

le%els *ut reduced >" receptors in malnouris!edc!ildren. +ecent studies !a%e s!o,n t!at serum leptinle%els and insulin/lie #ro,t! factor I 7I>F/I arereduced in *ot! marasmus and ,as!ioror)su##estin# t!at nutrient depri%ation leads to decreased

fat mass) insulin) and possi*l& I>F/1) suppressin#leptin) ,!ic! ma& in turn stimulate t!e !&pot!alamic/ pituitar&/adrenal a=is to increase cortisol and >"secretion. +elated studies !a%e s!o,n t!at >" could *e used t!erapeuticall& to restore somatic and muscle#ro,t! in an e=perimental model of -M. In controls)

an enric!ed diet promoted fat deposition alone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McGee+DW%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McMurray+DN%22%5BAuthor%5D










(!&mic atrop!& in malnutrition leads to loss of

cortical D4 ( cells. orrelation *et,een serumcorticosterone le%el and t!&mic atrop!& !as *eens!o,n in a murine model of protein malnutrition.+efeedin# re%ersed t!is effect. (!ese studies su##est

t!at increases in serum corticosterone o*ser%ed in-M could also tri##er apoptosis) contri*utin# to t!e

loss of differentiated ( cells 7>aulsc! et al. 1333.

Alt!ou#! t!e effects of infection and malnutrition onimmune response are interacti%e) t!e impact of eac!on immune response is also independent. A recente=amination *& Mis!ra and collea#ues of #raded -M

in c!ildren at ris for Mycobacterium tuberculosis

infection included stud& of response to a sin testaner#& panel) includin# --D. Impaired cellular immunit& ,as found in all #rades of malnutrition ,it!t!e e=ception of response to --D in #rade 1. ei#!t

loss is a common presentin# s&mptom in c!ildren ,it!acti%e M. tuberculosis infection. A recent stud& inadults !as s!o,n t!at *efore treatment) *ot! leptin and(NF/G le%els ,ere ele%ated and intercorrelated.Alt!ou#! c!an#es in *od& mass inde= 7;MI ,ere proportional to c!an#e in leptin durin# treatment and,ei#!t #ain ,as ac!ie%ed earl& in t!e course of

anti*iotic treatment) t!ere ,as no correlation *et,een;MI and leptin *efore or after treatment) (NF/G le%elsdid not c!an#e. -ost/treatment leptin and (NF/Gle%els did not correlate. (!us) t!e underl&in#dere#ulation of leptin and (NF/G promotes ,astin#7;eisel 2000.

-M seriousl& impairs immune response to some %ac/cines) suc! as ;>. Alt!ou#! ;> does not pre%ent

M. tuberculosis infection) immuni9ation in endemicen%ironments ma& in!i*it de%elopment of in%asi%edisease. "o,e%er) t!is protection ma& *e lar#el&

ineffecti%e in c!ildren ,it! -M) as s!o,n in a stud&of immuni9ed malnouris!ed c!ildren ,!o did notrespond to tu*erculin after immuni9ation) *ecameinfected) and ,ent on to de%elop disseminated disease.(!e control #roup of ,ell/nouris!ed c!ildren ,as sinlest responsi%e and !ad a modified disease e=pression

,it! #reater locali9ation and reduced !emato#enous

spread. In contrast to t!e impaired reaction of malnouris!ed c!ildren to ;>) immune response toot!er %accines ma& *e conser%ed. For e=ample)seroprotection ,as ac!ie%ed e%en in malnouris!edc!ildren ,it! !epatitis ; %accine) alt!ou#! t!e

o*ser%ed fre<uenc& of protecti%e response ,asreduced compared ,it! t!at of !ealt!& infants7'c!,en Macallan 2000.

+esponse to some pat!o#ens ma& appear to *eimpro%ed in some states of malnutrition. >enton and

collea#ues assessed incidence of malaria in c!ildren of

-apua Ne, >uinea) and found t!at increased !ei#!t

for ,ei#!t at *aseline predicted incidence of malariadurin# t!e &ear of stud&) ,!ereas l&mp!oc&teresponse to malarial anti#ens ,as lo,er amon# t!ese,asted c!ildren. "e,e%er) malarial incidence ,as not

different amon# ,ellnouris!ed compared ,it!malnouris!ed c!ildren) ,!en at stunted c!ildren ,ere

included in t!e anal&sis. Fur!er c&toine productionto,ard malarial anti#ens ,as actuall& #reater amon#t!e malnouris!ed *ut not amon# ,asted c!ildren)su##estin# t!at a fa%ora*le c&toine re#ulator& s!iftmi#!t *e t!e *asis of impro%ed response. Alt!ou#!stuntin# ma& *e considered an adapti%e !ost response

to prolon# nutrient depri%ation) t!e stress response isne#ati%el& affected) and t!is ,ould liel& !a%e adetrimental effect on immune response in acuteinfection 7;eisel 2000.

Increased incidence of infections is common in -MA lar#e lon#itudinal stud&) carried out o%er 1 &ear amon# undernouris!ed rural ;an#lades!i c!ildren) !ass!o,n t!at ,astin# and sin test aner#& indicatin#immune deficienc& ,ere lined to acute upper respirator& infections. 'ome infections ma& also *e pi%otal in en!ancin# t!e ris of malnutrition in

c!ildren. Dale and collea#ues !a%e s!o,n t!at &elicobacter pylori infection) common amon#>am*ian c!ildren) is stron#l& associated ,it! ot!er enteric infectious and c!ronic malnutrition in t!e post,eanin# period 7;eisel 2000.

NUTRIENT AND IMMUNE RESPONSE

'ettin#s in ,!ic! conditional nutrient re<uirements!a%e alread& *een identified include sur#ical stress in,!ic! #lutamine and ar#inine are re<uired for immune

reco%er& and conditions of rapid #ro,t! in ,!ic! t!eimpact of dietar& nucleotides can *e o*ser%ed.Fundamental <uestions for t!e future are liel& tofocus on t!e role of !ost #enes as ,ell) for e=ample)t!ose re#ulatin# iron uptae and c&toine receptor #ene pol&morp!ism 7unnin#!am +undles 2002.

In t!is discussion) effort ,ill *e made to distin#uis!indirect nutrient effects) ,!ic! are #eneral andapplica*le to all tissues) from direct actions in ,!ic!l&mp!oid tissues and immune response are affectedeit!er disproportionatel& or specificall&. 'imilarl&) t!e

mec!anism of nutrient action ma& differ accordin# tosettin# and concentration. -!armacolo#ic use of nutrients ma& !a%e immunomodulator& effectsdifferent from t!ose e=erted *& smaller amounts #i%ento ac!ie%e p!&siolo#ic repletion to normalle%els.(!ese differences ma& e=plain ,!&

supplementation a*o%e normal le%els ma& sometimes




*e associated ,it! a decline of immune response t!at

could not !a%e *een predicted from studies of repletion. (!e impact of an& supplementation is alsoaffected *& conditions in t!e !ost. -resence of infection) underl&in# illness) or immune deficienc&

ma& also affect response to nutrient administration)and correlations o*ser%ed in t!ese settin#s *et,een

immune response and nutrient le%el ma& not !old truein t!e !ealt!& !ost 7unnin#!am +undles 2002.

Micronutrients) trace elements) and %itamins presentin !a%e important re#ulator& effects on adapti%eimmune cell function. 'pecific nutrients suc! as sinc

support a (!1 c&toine response in ,!ic! interleuin7I/2 and interferon 7IFN/ are produced) ,!ereasot!er nutrients) suc! as %itamin A) t&picall& supportsecretion of (!2 c&toines) includin# I/4. I/) andI/10. (!erefore) t!e o%erall effect of t!e

microen%ironment is to dri%e immune response to,ardeit!er a (!1 or a (!2 response 7;eisel 200.

Man& nutrients interact ,it! ot!er immune re#ulator&molecules to influence immune response. B=amplesinclude t!e reported counterre#ulator& effect of %itamin B on prosta#landin B2 7->B2 suppression of

a c&clic adenosine monop!osp!ate 7AM- responseelement *indin# 7+B; protein. Mec!anisms of nutrient action often in%ol%e se%eral pat!,a&s and produce a ran#e of p!enot&pic effects. In t!e mouse)%itamin ;12 7co*alamin deficienc& reduces le%els of . immuno#lo*ulin 7I#M) and I#> and increases

le%els of I#B t!rou#! causin# a s!ift from (!1 to (!2response. Increased D8 ( cell num*er and N@ cellacti%it&) as ,ell as me#alo*lastic anemia) c!aracteri9e!uman %itamin ;12 deficienc&. Vitamins A and D !a%e *een intensi%el& studied as critical re#ulators of #enee=pression for *ot! #ro,t! and immune de%elopment.

Vitamin A deficienc& impedes retinol dependent si#/nals durin# em*r&onic de%elopment) and %itamin Asupplementation en!ances (!2 response to %irusessuc! as influen9a. Vitamin D acts as a nuclear receptor for tar#et #enes and also !as a re#ulator& influence onimmune cell differentiation 7;en#mar 1333

$ENETIC DE!ECT

AND CON$ENITAL DISEASE

-rimar& nutrient deficienc& occurrin# in c!ildren as a

sin#le entit& is usuall& t!e result of po%ert&) lac of ade<uate suppl&) or ot!er en%ironmental factors. +areinnate occurrences include t!e #enetic defect of 9incmeta*olism) acrodermatitis enteropat!ica) and defectsof copper in MenesK s&ndrome or ilsonKs disease."o,e%er) intae deficient of essential nutrient

re<uirements ma& *e caused *& altered meta*olism in

association ,it! an underl&in# con#enital condition)

disease) or acute illness and can also lead tomalnutrition and impaired !ost defense 7unnin#!amet al.133L Fraer et al. 2000.

on#enital t!&mic a*sence) Di>eor#eKs s&ndrome) isassociated ,it! recurrent infections) ,!ic! can *e

fatal. Ct!er de%elopmental anomalies t!at stem fromc!romosome 22<ll deletions comprisin# t!e A("/22 7cardiac defects) a*normal facies) t!&mic!&poplasia) cleft palate) and !&pocalcemia #roup of disorders ma& also !a%e clinicall& si#nificant immunedeficienc& in association ,it! reduced t!&mic

function. A 9inc fin#er #ene) HNF4) !as *eenidentified in t!e commonl& deleted re#ion 7McDade etal. 2001

NEONATAL AND IMMUNE RESPONSE

Neonates and infants must primaril& on innateimmunit&) alt!ou#! some components of innateimmunit& are not as functional in &oun# c!ildren as inadults 7>rie*el et al. 200. In #eneral) impairment of cell/mediated immunit& and reduction in p!a#oc&te

function are c!aracteristic of lo, *irt! ,ei#!t infants.omplement deficiencies are also an important causeof suscepti*ilit& to infections. (!e de%elopment of c&toine response is crucial for t!e differentiation of adapti%e immunit& in t!is period. o, *irt! ,ei#!tA>A infants respond ,ell to some immuno#ens suc!

as ;acille almette/>uerin 7;> ,it! respect to proliferati%e response to anti#en) 1/2 production in%itro) and sin test response to purified proteinderi%ati%e 7--D in %itro. o, *irt! ,ei#!t infantsalso tolerate and respond to immuni9ation ,it!dip!t!eria/tetanus/pertussis 7D(- *ut do not respond

effecti%el& to &aemophilus influenae t&pe ;. Furt!er maternall& ac<uired passi%e immunit&) assessed as#eometric mean anti*od& to %iruses and to *acteria) isreduced. (!e lo, *irt! ,ei#!t infant is!&po#amma#lo*ulinemic and suscepti*le tonosocomial infections) *ut intra%enous immune

#amma#lo*ulin is lar#el& ineffecti%e in reducin# t!ese

infections. Importantl&) studies !a%e also s!o,n t!att!e immune response of t!e premature infant is alsoaffected *& routine *lood transfusion to replace *looddra,n for clinical monitorin# 7arlson Hie#ler 1338.

(!e effect of nutrients in immune response candepend on t!e site of action. For e=ample) t!e #utassociated l&mp!oid tissue 7>A() t!&mus) spleen)re#ional l&mp! nodes) or immune cells of t!ecirculatin# *lood. (!e same nutrient ma& !a%e a

different mec!anism of action in %arious sites. For




e=ample) 9inc ma& potentiate to (!1 response

s&stemicall& and to (!2 responses at t!e le%el of >A(. +esponses are also affected *& ot!er !ostfactors) includin# t!e presence of infection or ot!er illness) sta#e of life) a#e) and anti#enic !istor&. it!

t!e principal e=ception of t!&mulin) t!e 9incdependent !ormone) !ormonal c!an#es !a%e *een

taen into account in studies of immune de%elopment."o,e%er) current e%idence su##ests t!at endocrinefactors affect *ot! innate and adapti%e immuneresponse 7;en#mar 1333.

(!e immune s&stem !as *een t!ou#!t of t,o

essentiall& separate) innate and adapti%e s&stemsrespondin# to t!e e%ol%in# needs of t!e or#anism indefense a#ainst pat!o#ens. (!e innate s&stem t!atmediates in immediate immune reaction t!at isindependent of specific anti#ens !as de%eloped to

reco#ni9e micro*ial t!rou#! identification of conser%ed micro*ial products) pat!o#en/associatedmolecular patterns) and to no, *& means of specific#ene products. (!us) in addition to uni<ue micro*ialmotifs) infected or pat!olo#icall& altered self can *eidentified as missin# or altered self. Adapti%eimmunit& !as *een di%ided conceptuall& accordin# to

cell t&pe and ori#in as t!e response of *one narro,deri%ed ; cells *elon#in# to t!e !umoral immunes&stem and t!&mus deri%ed ( cells of t!e cellular immune s&stem. (!rou#! anti#en encounter) pol&clonal ( cell responses *ecome refined to a morerestricted ( cell to a process t!at resem*les t!e affinit&

maturation of ; cells. Differentiation of cell functionand cell interactions are si#nificantl& determined *&t!e local microen%ironment. For e=ample) in t!e li%er)immune cells suc! as natural ( cells) ,!ic! !a%edistinct c&toine secretion patterns affectin# !ostresponse to anti#en. (!&mus independent (/cell

differentiation is also dominant in t!e #astrointestinaltract) as mediated *& suc! cells as t!e intraepit!eliall&mp!oc&te 7C9an et al .1338

A #ro,in# #eneral concern is t!at nutrient intae ma& *e su*optimal *ecause t!e diseases of prematurit&

impose an additional meta*olic *urden. Assessment of

selenium and 9inc !as s!o,n t!at le%els are lo,) e%en,!en intae follo,s current #uidelines 7Fraer et al.2000. -rotein and lipid intae ma& need to *eincreased) *ecause t!e de%elopment of t!e #ut and t!eimmune s&stem occurs interacti%el&) it is liel& t!at

nutrients ma& foster normal tolerant immune responseto,ard food anti#ens. 'upplementation ,it! dietar&nucleotides !as *een su##ested as a means of *eneficiall& affectin# t!e #ro,t! of t!e #ut in t!e premature infant t!rou#! influencin# intestinal permea*ilit& and a*sorption of macromolecules)

affectin# anti*od& response to,ard /lacto#lo*ulin

and G/casein. Martne9/Au#ustin and collea#ues !a%e

found t!at I#> anti*odies a#ainst t!e main anti#enic proteins in co,s mil ,ere #enerall& !i#!er ,!ennucleotide supplementation ,as pro%ided. (!isdifference reac!ed si#nificance for anti*od& to /

lacto#lo*ulin at 0 da&s of life ,!en #ut closure !adoccurred. 'tudies *& t!is #roup also su##est t!at I#A

and I#M !umoral immune response are en!anced *&nucleotide supplementation 7in et al.1338.

Fi#ure 2. (!is fi#ure indicates t!e role of nutrients in!o, t!e microen%ironment influences t!e production of c&toines *& t!e adapti%eimmune s&stem. A- E anti#en/presentin#cellL >I E #astrointestinalL IFN E

interferonL I E interleuinL N@ E naturaliller L (! E ( !elper.

(!e neonate re<uires micronutrients suc! as iron) 9incand selenium as ,ell as an ener#& diet. Vitamin A is

crucial for de%elopment of normal immune responseand for de%elopment of epit!eliali9ation in t!e lun#.'!enai and collea#ues !a%e s!o,n t!at air,a&infection in t!e mec!anicall& %entilated %er& lo, *irt!,ei#!t infant ,as associated ,it! reduced plasma%itamin A. "uman mil normall& pro%ides

*ioa%aila*le micronutrients suc! as 9inc) as ,ell assecretor& immuno#lo*ulin and #ro,t! factors. 'ome

maternal mil ma& *e lacin# in 9inc despite normalle%els in serum) and in suc! cases) *a*ies ma& de%elopa condition t!at is p!enot&picall& identical toacrodermatitis enteropat!ica. o, le%els of fatt&

acids) suc! as docosa!e=aenoic acid 7D"A) inmot!ers !a%e *een found to correlate directl& ,it! lo,le%els in malnouris!ed c!ildren. D"A is critical for %isual acuit& affect postnatal *rain #ro,t!) and alsoinfluences immune response t!rou#! in!i*itor& effectson t!e I/2 pat!,a&. (!e si#nificance of t!is for !ost

defense maturation of t!e immune s&stem re<uiresfurt!er stud& 7@ell& outts 2000.




'ecretor& I#A anti*odies in mil reacti%e a#ainst

anti#ens in t!e maternal #ut can *e protecti%e a#ainst#astrointestinal disease. +ecent studies s!o, t!at li%eimmune mediators in mil suc! as transfer #ro,t!factor 7(>F/ and solu*le D14) t!e *an pattern

reco#nition receptor) are liel& to *e e& elements intemperin# neonatal immune response. Maternal

malnutrition is associated ,it! a decline total mil I#A) and 4 and ma& affect pass transferredantimicro*ial defense. 'tudies su##est mil anti*od&le%els are to some de#ree conser%ed) ,!en maternalnutrition is inade<uate. Maternal ma& also *eimportant in influencin# t!e #radual s!ift in immune

polarit& in t!e neonate from (!2/t&pe s&stemicall&and (!1/t&pe response in t!e >A( to,ard t!e adult pattern in ,!ic! inflammator& immune response isup/re#ulated in t!e perip!er& and (!2 response predominates in t!e #ut 7;en#mar ' 1333.

!an#es in mucosal de%elopment occur in t!e net period in t!e conte=t of ma?or s!ifts in enteral intae)micro*ial e=posure) and immune cell maturation.eanin# time of en!anced ris of malnutrition andt!erefore of increased %ulnera*ilit& to infections. Normal intestinal #ro,t! is s!arpl& en!anced at

,eanin#) and t!is is mediated t!rou#! (/cell acti%ation *& food su*stances and micro*ial anti#ens andin%ol%es transient) locali9ed inflammator& response.+ecent studies !a%e s!o,n t!at t!is is accompanied *&increased e=pression of t!e I/2 receptor ande=pansion of G (/cell receptor/positi%e 7(+

cells 7Do!ert& et al. 1333.

MICRONUTRIENTS

AND IMMUNE !UNCTION

urrent studies su##est t!at muc! of t!e en!ancedsuscepti*ilit& to infections o*ser%ed in -M ma& *edirectl& related to micronutrient insufficienc&. >oodand collea#ues) ,!o proposed t!at deficienc& of certain e& trace element) especiall& 9inc) mi#!t *e t!edirect cause of immune deficienc& in t!e

malnouris!ed !ost. Iron) copper) and iodine

deficiencies are t!e most common trace elementnutrient deficits in Nort! America. 'eleniumdeficienc&) lie t!at of iodine) affects parts of t!e,orld ,it! lo, le%els in soil. Micronutrients are oftendeficient in #enerali9ed infections suc! as c!ronic

%iral illnesses and m& directl& cause impaired immuneresponse 7unnin#!am +undles 2002.o, dietar& intae of antio=idant nutrients can alsoinfluence response to infections and ma& lead to anunopposed inflammator& state. For e=ample) &. pylori

can lead to c!ronic #astritis caused *& acti%ated

p!a#oc&tes. Nair and collea#ues o*ser%ed t!at patients

,it! #astritis and peptic ulcer disease

c!aracteristicall& !a%e a lo, le%el of antio=idants in *ot! serum and mucosa ,!et!er or not &. pylori

infection ,as detected. +ele%ant studies in a mousemodel !a%e s!o,n t!at treatment ,it! antio=idants to

reduce #astric inflammation and to lo,er *acterialload. ;ennedsen and collea#ues o*ser%ed a s!ift from

a (!1 t&pe immune response to a mi=ed (!1(!2response) ,!ic! ,as dominated *& I/4 and IFN/ production 7'c!midt 133.

Micronutrients !a%e a crucial impact on immuneresponse) *ot! t!rou#! antio=idant effects and t!rou#!

modulation of c&toine e=pression. (race elementsand %itamins perform antio=idant functions t!rou#! participation in en9&me catal&9ed reactions. (!esereactions are essential to offset potential o=idati%edama#e caused *& free radical formation. (!ree

antio=idant en9&mes) t!e copper) 9inc and man#anesesupero=ide dismutases) re<uire trace metals for *iolo#ic acti%it&) micronutrients are pi%otal re#ulatorsof c&toine production. -arenteral nutrient preparations ma& not pro%ide ade<uate le%els of micronutrients suc! as %itamin B and selenium)causin# antio=idant deficienc&) ,!ic! ma& lead to

lipid pero=idation) a measure of o=idati%e stress7unnin#!am +undles 2002L 'c!midt 133.

CONCLUSION

Nutrient deficiencies ma& !a%e an indeli*le effect dur/in# critical periods of earl& de%elopment *& e=ertin#an imprintin# effect on t!e fundamental pro#ram of future de%elopment. (!is concept is supported *& t!edisco%er& of interactions *et,een neonatal nutritionalstatus and *lood pressure or co#niti%e a*ilit&. In t!e

c!an#in# social conditions of c!ild!ood in #eneralincreasin#l& fra#mented famil& life) no,led#e of nutrients t!at ma& affect t!e de%elopment of immuneresponse ,ill !a%e #reater critical importance for pre%enti%e effort support future !ost defense a#ainstne, pat!o#ens.

RE!ERENCES

;eisel) + 2000) OInteractions *et,een nutrition andinfectionP) in >( 'tricland 7ed) &unter's Tropical

Medicine and merging nfectious *iseases! 8t! edn); 'aunders) -!iladelp!ia) pp. 3/38.

;eisel) + 200) Malnutrition and mmune Response)retrie%ed Januar& ) 200) from!ttp:stinet.dtic.miloaioaiQ%er*E#et+ecordmetadata -refi=E!tmlidentifierEADA04884)

;en#mar) ' 1333) O>ut microen%ironment and

http://stinet.dtic.mil/oai/oai?&verb=getRecord&%20metadata%20Prefix=html&identifier=ADA048384







immune functionP) Curr +pin Clin $utr Metab

Care) %ol. 2) pp. 8/8.arlson) 'J Hie#ler) B 1338) ONutrient intaes and

#ro,t! of %er& lo, *irt! ,ei#!t infantsP) , Perinatol )%ol. 18) pp. 22/28.

unnin#!am) +undles) ') er%ia) J' 133)OMalnutrition and !ost defenseP) in A aler) J;

alins 7eds) $utrition in Pediair% -asic cience

and Clinical /pplication) 2nd edn. Marcel Deer)ondon) pp. 23/0.

unnin#!am +undles) ' 2002) OB%aluation of nutrient interaction in immune functionP in -alder 7ed) $utrition and immune function! C/- )

pp. 21/3.unnin#!am) +undles) ') McNeele&) D)

Anan,oranic!) JM 2002) OImmune response inmalnutritionL) in B+ 'tie!m) "D Cc!s) JAinelstein 7eds) mmunologic *isorder in nfant

and Children) t! edn) 2002.Do!ert&) JF) >olden) M") +emic) D>) >riffin) >B

1334) O-roduction of interleuin/ and tumor necrosis factor/alp!a in %itro is reduced in ,!ole *lood of se%erel& malnouris!ed c!ildrenP) Clin ci)%ol. 8) pp.4/1.

Fraer) -J) @in#) B) aao) () Vollmer) ( 2000)

O(!e d&namic lin *et,een t!e inte#rit& of t!eimmune s&stem and 9inc statusP) , $utr ) %ol. 10) pp.133/140.

>aulsc!) (A) @andl) 'M) Dono%an) 'M) a&man) D@ 1333) P>ro,t!. !ormone promotes somatic andseletal muscle #ro,t! reco%er& in rats follo,in#

c!ronic protein ener#& malnutritionP) , $utr ) %ol.123) pp. 828/8.

>rie*el) -J) 'c!oonder,oerd) M) ;a*iu) A)+ntogeny of the immune response% effect of protein

energy malnutrition in neonatal calves% retrie%edCcto*er 1) 200) from

!ttp:!i#!,ire.stanford.educ#imedlinepmidL1411Qma=tos!o,E"I('E!itsE+B'$(FC+MA(E1andore=acttitleEandfullte=tER22Cnto#en&oft!eimmuneresponseR22andore=actfullte=tEandsearc!idE1FI+'(I

NDBSE10sortspecErele%anceresourcet&peE"

I() @ell&) D outts) A> 200) OBarl& nutrition and t!e

de%elopment of immune function in t!e neonateP) Proc $utr oc) %ol. 3) pp. 1/18.

in) B) @olani) J>) o,r&) 'B 1338) ONutritional

modulation of immunit& and t!e inflammator&responseP) $utrition) %ol. 14) pp. 4/0.

McDade) () ;ec) ) @u9a,a) ) Adair) ' 2001)O-renatal under/nutrition and postnatal #ro,t! areassociated ,it! adolescent t!&mic functionP) , $utr )%ol. 1) pp. 122/121.

Mc>ee) D McMurra&) DN) The effect of protein

malnutrition on the g/ immune response in mice!

retrie%ed Decem*er 8) 2000) from!ttp:,,,.nc*i.nlm.ni!.#o%entre9<uer&.fc#iQcmdE+etrie%ed*E-u*Medlist5uidsE21doptEA*stract)

C9an) ") Cl#un) N) 'asma9) B) et al. 1338)ONutrition) immunit& and infections: ( l&mp!oc&te

su*populations in protein/ener#& malnutritionP) ,

Trop Pediatric) %ol. 3) pp. 2/20.'c!midt) @ 133) OInteraction of antio=idati%e

micronutrients !ost defense mec!anisms. A criticalre%ie,P) nt , 0itam $utr Res) %ol. ) pp. 0/11.

'c!,en) A Macallan) D 2000) O(u*erculosis)

malnutrition and ,astin#P) Curr +pin Clin $utr

Metab Care) %ol. ) pp. 28/231.'crims!a,) N' 'an >io%anni) J+ 133) O'&ner#ism

of nutrition) infection) and immunit&: an o%er%ie,P) /m , *in $utr ) %ol. ) pp. 4T.

http://highwire.stanford.edu/cgi/medline/pmid;3134116?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=%22Ontogeny+of+the+immune+response%22&andorexactfulltext=and&searchid=1&FIRSTINDEX=10&sortspec=relevance&resourcetype=HWCIT











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