Stress and Immune System

7/21/2019 Stress and Immune System

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STRESS AND IMMUNESYSTEM

C. SINGGIH WAHONO

Divisi Reumatologi-Imunologia!"SM# I$D RSSA"#% U&

email' singgi()*a(ono+,a(oo.om



Psychoneuroimmunology PNI/

Inte0a1si anta0a 20oses 2si1ologis3engan sistem sa0a4 se0ta sistemimun.

Te005a3i 1e05asama anta0a !e0!agai3is2lin ilmu' 2s,(olog,6

neu0osiene6 immunolog,6en3o0inolog,6 2(,siolog,6 in4etious3isease6 0(eumatolog,6 et.





E9te0nal vs Inte0nal St0esso0

• E9te0nal st0esso0s' ling1ungan 8si1misal' n,e0i6 su(u 3ingin atau2anas/6 ling1ungan 3engan st0es2si1ologismisaln,a' suasana 1e05a,ang ti3a1 men3u1ung6 (u!ungananta0 manusia ,ang ti3a1 !ai1/.

• Inte0nal St0esso0s' 8si1 in4e1si6in:amasi/6 2si1ologis.



St0esso0 Time Win3o*s

Imme3iate aute 2(ase tim!ul 3alam (itungan menit/ the“fght/ight” response6 me0u2a1an 0ea1si te0(a3a2 anaman,ang te05a3i sege0a'

Misaln,a' 1e!isingan6 isolasi6 1ela2a0an6 in4e1si se0ius6

memi1i01an a3an,a anaman6 3ll. S(o0t-te0m st0esso0s !e0langsung !e!e0a2a (a0i sam2ai

minggu/

Misaln,a' u5ian6 2in3a( 0uma(6 2asa 1e!a1a0an6 3ll.

C(0oni st0esso0s !e0langsung !e!e0a2a !ulan sam2ai!e0ta(un-ta(un/' situasi ,ang !e0langsung lama 3an nai1 tu0un6

misaln,a' me0a*at anggota 1elua0ga ,ang men3e0ita2en,a1it Al;(eime0<s 6 te1anan tinggi 3item2at 1e05a ,ang!e0langsung te0us6 1eti3a1 (a0monisa =n 2e01a*inan6

1emis1inan6 3ll.

>?



Jalur Stress

Corticotropinreleasing hormon(CRH)

Adrenocorticotrop

hormone(ACTH)



STRESS E##ECTS

Imme3iate

e@et E4e1sege0a/ Inte0me3iate e@et

$0olonge3 e@et

•S,m2at(etine0vous 0es2onse•E2ine2(0ine an3no0e2ine2(0ine0elease3• Time - to Bseon3s•i1e a 2(one all

•A30enal 0es2onse•E2ine2(0ine an3no0e2ine2(0ine0elease 40oma30enal me3ulla•

Time- ? to B?seon3s•i1e a teleg0am

•ACTH6vaso20essin an3

t(,0o9ine a@etva0ious meta!oli20oesses• Time - minutes6(ou0s6 3a,s o0

*ee1s•i1e an ove0nig(t



&agaimana St0ess i1ut !e02e0an3alam tim!uln,a 2en,a1it7

>



&agaimana St0ess

mem2enga0u(i sistem Imun7



Innate and adaptive immunity



T (el2e0

T(>

T(

A$C

CDF

CDF

MHC

MHC >

(el2

i0us in4ete3 ell

Int0aellula0 mi0o!es"

vi0us

& ell

$lasma ell

Ma0o2(age

BIRDI!" #$ ADAPTI! I%%&NIT'

Antigen 2(ago,tose3!, A$C

E@eto0 T ,tol,ti

T ,tol,ti



T(> an3 T( ,to1ines



• el imun – Mem2un,ai 0ese2to0 untu1 (o0mon 3an

neu0ot0ansmite0

• *aringan +im,oid (lim,onodi- – inne0vate3 !, t(e autonomi ne0vous

s,stem ANS/

– No0a30ene0gi ne0ve t0ats in t(e t(,musan3 s2leen



• St0esso0s ausing in:ammation20oess6 ativate immune s,stemto signal t(e !0ain o0 ativate

ne0ves nea0!, t(at signal t(e !0ain• Ativate (,2ot(alamus to initiate

asa3e (o0mones 0elease3 40om

2ituita0, an3 a30enal glan3 ausingin0ease3 o4 gluoo0tioi3o0tisol/



J



MODERATING VARIABLESGenetic predispositionPrevious life experiencesopin!Soci"l support

STRESSOR

Ps#c$olo!ic"l Stress% &ESNO

'&POT'ALAMI

ATIVATION

R'

PIT(ITAR& )ATORS

ACTH

S&MPAT'ETI ATIVATION

Norepinephrine

Medull"

ortex

Adren"l Gl"nds

IMM(NE S&STEM

GL(OORTIOIDS

EPINEP'RINE

J



H$A A9is

GOODMAN K GIMANLS6??





NE an3 e2ine2(0ine an alte0l,m2(o,te mig0ation'

Imme3iate e92osu0e B? min/

l,m2(o,tes6natu0al 1ille0 ells

onge0 e92osu0e 3a,s/

N% ells



NE an alte0 innate an3 a3a2tiveimmune 4untion in o0gans an3 in

i0ulation'

– #ine tunes immune 0es2onses6

allo*ing 4o0 ui1 a35ustments*it(in minutes/

– S(i4t 40om T(> to T(



eu1o,tes e920ess gluoo0tioi3 0ee2to0s'

o0tisol ats on gluoo0tioi3 0ee2to0s to (ave t(e4ollo*ing e@ets

in(i!it l,m2(o,te 20oli4e0ation

in(i!it 20o3ution o4 20o-in:ammato0, ,to1ines

S(i4t 40om T(> to T( ell ativit, !, stimulatings,nt(esis o4 I->?6 I-

>>



Innate Immune S,stem Mo!ili;ation int(e Imme3iate Aute $(ase o4 a St0esso0

Re3ist0i!ution o4 immune ellsin0ease in leu1o,tes in !loo3/

In0ease in innate6 non-s2ei8immunit, in0ease3 N% ell ativit,/

De0ease in s2ei8 immunit,

>>

>



Alte0ations in S2ei8 Immunit, 4ollo*ingE92osu0e to S(o0t-te0m St0esso0s'

De0ease in T(> ellula0 immune

0es2onse e.g.6 20oli4e0ative 0es2onseo4 l,m2(o,tes/

In0ease in T( (umo0al immunit,e.g.6 T( ,to1ine 20o3ution/

>

>B



Alte0ations in Non-s2ei8 an3 S2ei8 Immunit,4ollo*ing E92osu0e to C(0oni St0esso0s'

De0ease in both T(> ellula0 an3 T((umo0al immune 0es2onse e.g.6 lo*e0

anti!o3, tite0s to (e2atitis & vainesP/

De0ease in innate6 non-s2ei8 immune0es2onses e9e2t in:ammato0, ativit,/

$e0sistent in:ammato0, ativit, e.g.6in0ease3 20o-in:ammato0, ,to1ine

20o3ution/

>B

>



E@ets o4 St0ess on t(e ImmuneS,stem De2en3 not Onl, on Timing

!ut C(a0ate0istis o4 t(e $e0son

Immune e@ets a0e st0onge0 int(ose *(o'A0e ol3e0

Mo0e 3e20esse3ess su22o0te3

>

?



Adrenal Cortex

Cortisol

Anterior Pituitary

Hypothalamus

CRH

ACTH

tressors

immediate.acutephase hort.term.days/0ee1s Chronic.months/years

?

>



Adrenal Cortex

Cortisol

Anterior Pituitary

Hypothalamus

CRH

ACTH

Immune CellGCR

Co0tisol su220essesimmune 4untionssu( as 20o-

in:ammato0, ,to1ine20o3ution via t(egluoo0tioi30ee2to0 GCR/.

>



Adrenal Cortex

Cortisol

Anterior Pituitary

Hypothalamus

CRH

ACTH

Immune

Cell

GCR

&ut st0ess-Q INCREASES 20o-in:ammato0, ,to1ine20o3ution

One me(anism' Gluoo0tioi3Resistane' st0ess in3ue33o*n0egulation o4 GCR o0tisolannot 0est0ain 20o-in:ammato0, ,to1ine20o3ution so ,to1ine

20o3ution in0easesanimal"(uman stu3ies/



tress 2 related

Diseases



Chronic stress related toseveral health pro3lems

• Hea0t 3isease

• Dia!etes• Ule0s• G0o*t( 20o!lems• Immune s,stem su220ession• o*e0 su0vival 0ates *it( ane0





Inte0ations among T(e En3o0ine6 ent0al ne0vous Kimmune s,stem

St0esso0

C N S

Immunes,stem

En3o0ines,stem

E n 3 o - 0 i n

e

( o 0 m

o n e

$ i t u i t a 0 ,

( o 0 m

o n e

I m m u n o t 0 a n s m

i t

t

e 0

$ i t u

i t a 0 ,

2 e 2 t i 3

e s a

n 3

o t ( e 0 n

e u 0 o 2 e 2 t i 3

e s

En3o0ine(o0monesSte0oi3s6 20olatin6et



A0e t(ese st0ess-in3ue3immunologi (anges

liniall, signi8ant7

Do t(e, ont0i!ute to 3iseaseonset o0 aele0ate 3iseaseou0se7





Me3iato0s o4 St0ess-0elate3 C(angesin Woun3 Healing

3iminis(e3 mononulea0 ellt0a1ing to t(e *oun3 site

0e3ue3 e920ession o4 ,to1ine6(emo1ine6 g0o*t( 4ato0 genes

3e0ease3 20o3ution o4 20o-in:ammato0, ,to1ines in *oun3

envi0onmentP



E@et o4 st0ess on Cane0

De0ease ellula0 immune 0es2onseinnate K a3a2tive/ against ane0

De0ease3 DNA 0e2ai0 a2ait,

In(i!it ane0 ells a2o2tosis

&e(avio0al t(e0a2, an in0easeimmune 0es2onse against ane0



E@et o4 St0ess onAutoimmune 3isease

#la0e o4 some autoimmune

3iseases6 e6g. ' SE6 RA6 SSA6 et.





Inte0ventions to en(aneimmunoom2etene

AIDS 2atients *(o !ene8te3 40ome9e0ise an3 st0ess 0e3ution

inte0vention6 ' im20ovement in T CDF "TCDF

0atios6

CDF T ell ounts6N%-ell ,toto9iit,.

i (




Rela9ation ma, mute e@ets o4st0ess'

(ig(e0 N% ellativit, a4te00ela9ation inte0vention

Re3ues 20o-in:ammato0,,to1ines

Cellula0 immunit, en(ane3

I i (




&ette0 N% ell ativit, in !0eastane0 2atients *as 0elate3 to'

Hig( ualit, emotional su22o0t40om a s2ouse6

$e0eive3 2s,(osoial su22o0t

40om t(e 2atient<s 2(,siianAtivel, see1ing soial su22o0t

H Mi (t I 4 ti # t( #i l3



Ho* Mig(t In4o0mation #0om t(e #iel3o4 $s,(oneu0oimmunolog, In:uene

You0 Clinial $0atie7

As1 a!out li4e st0esso0s s(o0t

te0m an3 (0oni/6 im2at on4untioning As1 a!out (o* a 2atient is o2ing6

soial su22o0ts. Does it (el27

Reogni;e t(at vainations ma,!e less 20otetive 3u0ing st0ess4ultimes onsi3e0 ot(e020eautions/

Ho* Mig(t In4o0mation #0om t(e



Ho* Mig(t In4o0mation #0om t(e#iel3 o4 $s,(oneu0oimmunolog,In:uene You0 Clinial $0atie7

Reogni;e t(at *oun3 (ealing ma, !ein:uene3 !, st0ess

Reogni;e t(at immune 4untions ma,

!e a@ete3 !, t(e use o4 30ugs t(atin:uene t(e ANS o0 gluoo0tioi3se.g.6 β-!lo1e0s/.

As1 a!out t(e0a2, an3 ma1e

0eommen3ations an3"o0 0e4e00als asnee3e3 1no* *(at is availa!le in t(eommunit,/.

0eogni;e t(e limitations in 1no*le3ge*(en 2atients as1 a!out *(et(e0 a

given t(e0a2, visuali;ation6 et/ an



Stress and Immune System

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