MEKANISME PENYAKIT INFEKSI DALAM KONTEKSNYA DENGAN PSIKONEUROIMUNOLOGI

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MEKANISME PENYAKIT INFEKSI

DALAM KONTEKSNYA DENGAN

PSIKONEUROIMUNOLOGI

Oleh : Joni Haryanto

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PENDAHULUAN



Psikoneuroimunologi

neologism

– Psiko Psiko psikologipsikologi

– Neuro_Neuro neurologineurologi

– ImunologiImunologi



Robert Ader (2000) mrpk discipline-hybrid



Konsep

nerve – immune system bidirectional



Perlu pemahaman yg sama ttg stres dan

stresor

– Stres, mrpk lingk yg tidak nyaman bagi kehidupanStres, mrpk lingk yg tidak nyaman bagi kehidupan

– Menurut Eric Lindermann & G Caplan; stres ad Menurut Eric Lindermann & G Caplan; stres ad kondisi psikis yg merasa terancam

kondisi psikis yg merasa terancam

– Hans Selye; pendekatan medikofisiologis yaitu stres Hans Selye; pendekatan medikofisiologis yaitu stres mrpk perubahan biologis saat terpapar stresor

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STRES & ADAPTASI

 Stres mempunyai 3 tahapan :Stres mempunyai 3 tahapan :

– ActivationActivation – ResistanceResistance – Exhaustion Exhaustion

 Menurut Selye triad GAS, mrpk manifestasi dr respon Menurut Selye triad GAS, mrpk manifestasi dr respon

biologis non-spesifik dr stresor

 Stresor ad stimuli yg menyebabkan stresStresor ad stimuli yg menyebabkan stres

 Persepsi stres, mencerminkan proses pembelajaran yg Persepsi stres, mencerminkan proses pembelajaran yg

menghasilkan kognisi tertentu

 Menurut Watson ; Menurut Watson ; Psychology as science of behaviorPsychology as science of behavior  Para Para behaviorismbehaviorism ; bagaimana dg ; bagaimana dg nature vs nurturenature vs nurture  Menurut Weiten (2004) psikologi mrpk proses fisiologi Menurut Weiten (2004) psikologi mrpk proses fisiologi

dan kognisi

 Dhabhar & McEwen (2001) stimuli Dhabhar & McEwen (2001) stimuli stress perceptionstress perception

seterusnya menimbulkan

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PSIKOLOGI

 Ilmu yg mempelajari ttg perilakuIlmu yg mempelajari ttg perilaku

– OvertOvert

– Covert Covert

 Classical Pavlovian conditioningClassical Pavlovian conditioning mrpk suatu mrpk suatu learning learning

process

process dlm membentuk kognisi dlm membentuk kognisi

 Menurut Ader (1964) Menurut Ader (1964) learning process learning process dpt menentukan dpt menentukan koping individu

koping individu

 Skinner (Skinner (behaviorismbehaviorism) individu tdk akan mengulang ) individu tdk akan mengulang aktivitas yg merugikan

aktivitas yg merugikan

 Sigmund Freud (1856-1939) ; konsep Sigmund Freud (1856-1939) ; konsep unconcious unconcious mrpk mrpk determinan penting dlm dr

determinan penting dlm dr behaviorbehavior

 Watson’s behaviorismWatson’s behaviorism yaitu pemikiran ttg yaitu pemikiran ttg stimulus – stimulus –

response realtionship

response realtionship..

 Dhabhar & McEwen yg menghubungkan konsep Dhabhar & McEwen yg menghubungkan konsep Lindermann – Caplan & Hans Selye

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NEUROTRANSMITER

 Suatu sinyal kimia yg mampu berperan sbg alat Suatu sinyal kimia yg mampu berperan sbg alat

komunikasi sel

 Melalui gap junctions membentuk hubungan sitoplasma Melalui gap junctions membentuk hubungan sitoplasma

antar sel yg berdekatan

 Parakrin disekresi oleh sel dan berdifusi ke sel Parakrin disekresi oleh sel dan berdifusi ke sel

didekatnya

 Autokrin berefek pd sel yang mensekresiAutokrin berefek pd sel yang mensekresi

 Endokrin ad hormon yg masuk kedalam darah dan Endokrin ad hormon yg masuk kedalam darah dan

hanya utk sel target yg mempunyai reseptor spesifik

 Sinyal listrik pd neuron mengakibatkan lepas Sinyal listrik pd neuron mengakibatkan lepas

neurotransmiter yg berdifusi mlli celah kecil ke sel

target

 Neuron melepaskan neurohormon dan hanya sel yg Neuron melepaskan neurohormon dan hanya sel yg

memiliki reseptor yg memberikan respon

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SINAPS DAN NEUROTRANSMITER



Sinaps ad titik temu antara neuron dan sel target

Setiap sinaps terdiri dari 3 bagian ;

 terminal akson presinaptik_{terminal akson presinaptik}

 synaptic cleftsynaptic cleft (celah antar sel)_{(celah antar sel)}  membran sel postsinaptik_{membran sel postsinaptik}



Berdasarkan efeknya thdp potensial membran

neuron postsinaptik dibagi atas ;

– Excitatory synapseExcitatory synapse

– Inhibitory synapseInhibitory synapse



Berdasarkan stimulusnya, sinap dibagi atas ;

o Electrical synapseElectrical synapse

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Klasifikasi Neurotrsnmiter :



molekul kecil, transmiter cepat spt : acetylcholine, molekul kecil, transmiter cepat spt : acetylcholine,

amines, amino acids & NOamines, amino acids & NO



molekul besar, hampir semua polipeptida yg molekul besar, hampir semua polipeptida yg umumnya aktif sbg hormon

umumnya aktif sbg hormon

 AcetylcholineAcetylcholine disebut disebut cholinergiccholinergic

 AminesAmines : : dopamin, norepinephrine, epinephrine,dopamin, norepinephrine, epinephrine,

serotonin, histamin.

 Amino acidsAmino acids : : glutamate, aspartateglutamate, aspartate (eksitasi) dan (eksitasi) dan glycine

glycine, GABA (inhibisi), GABA (inhibisi)

 GasesGases : NO, CO : NO, CO

 PurinesPurines : adenosine, AMP, ATP : adenosine, AMP, ATP  Lipid : Lipid : anandamide anandamide

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SISTEM SARAF OTONUM



Merupakan bagian sistem saraf yg mengatur

fungsi viseral



Efeknya cepat dalam hitungan detik



Diaktivasi oleh pusat-pusat di medula spinalis,

batang otak, hipotalamus serta bgn dr limbik



Ditransmisi oleh :

 _{sistem saraf simpatis}_{sistem saraf simpatis}

 sistem saraf parasimpatis_{sistem saraf parasimpatis}



Serat saraf mensekresi :

 serat cholinergic_{serat cholinergic} acetylcholineacetylcholine

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SISTIM LIMBIK



Merupakan regio paling primitif cerebrum



Terdiri atas :

 Amygdala_Amygdala emosi & memoriemosi & memori

 Hyppocampus _Hyppocampus learning process learning process & & memori

memori



Berperan sbg penghubung antara fungsi

kognitif (reasoning) dan respon emosi spt rasa

takut dll



Cortex Cerebri mempunyai 3 area :

 area sensori _{area sensori} persepsi_persepsi  _{area motorik}_{area motorik} _pergerakan_pergerakan

 area asosiasi_{area asosiasi} mengintegrasi informasi dan _{mengintegrasi informasi dan} tingkah laku

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IMUNOLOGI



Ilmu yg mempelajari ttg ketahanan tubuh



Terdiri atas

:

• Innate immunityInnate immunity

• Adaptif immunityAdaptif immunity



Sistem ketahanan tubuh yg

mempertahankan tubuh tetap sehat



Mampu membedakan zat asing (non-self)

dari zat yg berasal dr tubuh sendiri (self)



Dalam kondisi patologis tdk mampu

membedakan non-self & self.

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SKEMATIK

UMUM INTERAKSI SISTEM

SARAF DAN SISTEM IMUN

  General schematic of the General schematic of the

interactions between the interactions between the

nervous system and the nervous system and the

immune system mediated immune system mediated

primarily by soluble, secreted primarily by soluble, secreted

products of cells in each products of cells in each

system. system.

 The prevailing view is that The prevailing view is that

these two complex systems these two complex systems

interact and share in the effort interact and share in the effort

of promoting organismic of promoting organismic homeostasis by the use of homeostasis by the use of

mediators produced in each mediators produced in each

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 The immune system, typified by The immune system, typified by

the schematic lymph node on the

left, responds to antigenic stimuli

and produces mediators that

impact neural activity and

neurosecretion of peptides and

cytokines, which modulate the

immune response to the antigen.

 This circuit is viewed as a This circuit is viewed as a

bidirectional response bidirectional response

system in which the immune system in which the immune

system responds to system responds to

noncognitive stimuli, such noncognitive stimuli, such

as infectious agents, and as infectious agents, and

signals the nervous system, signals the nervous system, which responds to cognitive which responds to cognitive

stimuli such as stimuli such as

neurochemicals, cytokines, neurochemicals, cytokines, and physical and emotional and physical and emotional stimuli and, in turn, signals stimuli and, in turn, signals

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NEUROMODULASI PADA SISTEM SARAF

 Noradrenergic fibers from the Noradrenergic fibers from the

spinal ganglia enter the spleen spinal ganglia enter the spleen

through the trabecular through the trabecular

meshwork, distribute around meshwork, distribute around

and innervate areas of and innervate areas of

accumulated lymphocytes accumulated lymphocytes

called the white pulp and the called the white pulp and the

periarteriolar lymphatic periarteriolar lymphatic

sheaths, which consist of dense sheaths, which consist of dense

aggregates of lymphocytes. aggregates of lymphocytes.

 During antigenic stimulation, During antigenic stimulation,

there is increased production of there is increased production of

norepinephrine, substance P, norepinephrine, substance P, somatostatin, and vasoactive somatostatin, and vasoactive

intestinal peptide, which intestinal peptide, which regulates blood flow and regulates blood flow and

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AKTIVITAS NORADRENERGIK

PADA MAKROFAG (APC)

 Antigen presentation by Antigen presentation by

macrophages and the lymphocyte

response are modulated by

noradrenergic activity.

 Norepinephrine and neuropeptides Norepinephrine and neuropeptides

may act on the APC, suppressing

IL–1 production and thereby

preventing lymphocyte activation

and cell division. Alternatively,

noradrenergic nerve activity may

act directly on the lymphocyte,

suppressing activation and

mitosis.

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AKTIVITAS DI PEMBULUH DARAH

 Vasoactive intestinal Vasoactive intestinal

peptide (VIP) can alter

lymphocyte movement and

localization by stimulating

the expression of

intercellular adhesion

molecule 1 (ICAM–1) and

lymphocyte function–

associated antigen 1 (LFA–

1) on vascular endothelial

cells and lymphocytes,

respectively.

 Once receptor–ligand Once receptor–ligand

binding occurs, the

lymphocytes can migrate

from the blood vessel into

the tissues

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ACTH DAN GLUKOKORTIKOIDS

 Adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH) produced in the

(ACTH) produced in the

pituitary gland stimulates the

production of glucocorticoids

by the adrenal glands (A).

 These naturally occurring These naturally occurring steroids alter lymphocyte

steroids alter lymphocyte

recirculation and cytokine

production. Removal of the

pituitary or adrenal gland

interrupts the pathway

involved in the production of

ACTH and glucocorticoids (B).

 There is accumulating There is accumulating

evidence that lymphocytes can

produce biologically active

neurohormones such as ACTH

and thus may serve as an

alternative source of such

mediators

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ACTH MENEKAN Ab

 ACTH suppresses ACTH suppresses

antibody production

in vitro

in vitro. The hormone . The hormone may act on the

may act on the

antigen presenting

cell, the T helper cell,

or the B cell, or all

three, inhibiting

cytokine–mediated

growth and

maturation of the

antibody–producing

cells

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Production of cytokines by cells in the

immune system (A) and nervous system (B).

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Peran molekul MHC

 Induction of expression Induction of expression

of MHC class I and class

II molecules on glial cells

allows these cells to

present antigens to

lymphocytes.

 Glial cells (microglia, Glial cells (microglia,

astrocytes and oligo–

dendrocytes) respond to

such cytokines as IFNg

and TNFa, express class I

and/or class II molecules,

and present antigens to

lymphocytes.

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KOMUNIKASI DUA ARAH

 The homeostatic The homeostatic

balance maintained

by the responses of

the immune system

and nervous

system. These

systems interact

following the receipt

of stimuli. Cytokines

and neuromediators

elicit and modulate

the responses of

cells in both

systems.

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HPA-AXIS

 Some neuroendocrine Some neuroendocrine pathways to the

pathways to the

immune system. Many

of the hormones

released by the

hypothalamus,

pituitary and endocrine

glands affect the

activity of

lymphocytes.

 In stress, hormones In stress, hormones and neurotransmitters

and neurotransmitters

from the adrenal

cortex (corticosteroids)

and medulla

(principally

catecholamines and

enkephalins) are

especially important.

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SISTEM SARAF DAN SISTEM IMUN

 Some immune system Some immune system

pathways to the nervous

system. Various cytokines

released by activated

cells of the immune

system modulate the

activities of the

autonomic and

neuroendocrine systems.

 In addition, lymphocytes In addition, lymphocytes

and other immune cells

release some

neurotransmitters and

neurohormones.

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PSIKONEUROIMUNOLOGI

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EFEK STRESOR TERHADAP IMUNITAS

 Tingkat stres merambatkan sinyal ke HPA axis yg Tingkat stres merambatkan sinyal ke HPA axis yg

akhirnya sampai ke sel imun.

 Konsep triple S (Konsep triple S (stress signaling substancesstress signaling substances) mrpk alat ) mrpk alat

komunikasi antar sel saat sel mengalami stres.

 Sinyal tsb ad :Sinyal tsb ad :

 Corticotropin releasing hormone (CRH)Corticotropin releasing hormone (CRH)  Arginine vasopressine (AVP)Arginine vasopressine (AVP)

 Proopiomelanocortine (POMC)Proopiomelanocortine (POMC)  Proenkephaline (PENK)Proenkephaline (PENK)

 ProdynorphineProdynorphine

 Adenocorticotropine hormon (ACTH)Adenocorticotropine hormon (ACTH)  EpinephrineEpinephrine

 Nor-epinephrineNor-epinephrine

 GlucocorticoidGlucocorticoid meliputi semua neurohormonal meliputi semua neurohormonal  SitokinSitokin

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GLUKOKORTIKOID

 Dihasilkan oleh kelenjar adrenalDihasilkan oleh kelenjar adrenal  Menginduksi apoptosisMenginduksi apoptosis

 Menginaktivasi NF-Menginaktivasi NF-__B yg mrpk promoter sitokinB yg mrpk promoter sitokin  Menghambat transkripsi gen IL-2Menghambat transkripsi gen IL-2

 Pemicu downregulation ekspresi MHC IIPemicu downregulation ekspresi MHC II  Menekan produksi IL-2 & IFN-Menekan produksi IL-2 & IFN-γγ

 Meningkatkan produksi IL-4Meningkatkan produksi IL-4

 Bekerja sama dg hormon stres lain spt Bekerja sama dg hormon stres lain spt katekolamin

katekolamin

 Efek stresor ekhausted dpt menurunkan imunitas Efek stresor ekhausted dpt menurunkan imunitas baik alami maupun didapat.

baik alami maupun didapat.

 Ini sangat dipengaruhi oleh proses pembelajaran Ini sangat dipengaruhi oleh proses pembelajaran individu terhadap stresor

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MEKANISME INFEKSI



Triple S, mrpk substansi yg digunakan sel saraf

dan sel imun utk berkomunikasi.



Stresful live events

menurunkan fagositosis

makrofag dan fungsi neutrofil



Hiperaktif aksis HPA berhubungan dg

kerentanan infeksi, karsinogenik & penyakit

autoimun



Psikoneuroimunologi cukup jelas bisa diterima

bahwa :

 Kerentanan individu terhadap infeksi oleh karena Kerentanan individu terhadap infeksi oleh karena

kemampuan koping

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PNI & INFLAMASI

 Inflamasi mrpk respon jaringan vaskuler terhadap Inflamasi mrpk respon jaringan vaskuler terhadap

patogen

 Inflamasi yg berhasil akan diakhir dg proses Inflamasi yg berhasil akan diakhir dg proses

penyembuhan

 Inflamasi mrpk satu diantara 4 bentuk imunitas alamiInflamasi mrpk satu diantara 4 bentuk imunitas alami  Semua stimuli yg membangun Semua stimuli yg membangun stress perceptionstress perception dapat dapat

menurunkan imunitas, shg meningkatkan kerentanan

terhadap infeksi

 Kualitas Kualitas stress perceptionstress perception menghasilkan kognisi dan menghasilkan kognisi dan

bentuk koping individu yg dapat memodulasi sistem

imun.

 Inflamasi terjadi krn keluarnya mediator spt bradikinin, Inflamasi terjadi krn keluarnya mediator spt bradikinin,