MEKANISME PENYAKIT INFEKSI
DALAM KONTEKSNYA DENGAN
PSIKONEUROIMUNOLOGI
Oleh : Joni Haryanto
PENDAHULUAN
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Psikoneuroimunologi
– Psiko
– Neuro
– Imunologi
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psikologi
neurologi
neologism
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 kehidupan
– Menurut Eric Lindermann & G Caplan; stres ad
kondisi psikis yg merasa terancam
– Hans Selye; pendekatan medikofisiologis yaitu stres
mrpk perubahan biologis saat terpapar stresor
STRES & ADAPTASI
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Stres mempunyai 3 tahapan :
– Activation
– Resistance
– Exhaustion
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Menurut Selye triad GAS, mrpk manifestasi dr respon
biologis non-spesifik dr stresor
Stresor ad stimuli yg menyebabkan stres
Persepsi stres, mencerminkan proses pembelajaran yg
menghasilkan kognisi tertentu
Menurut Watson ; Psychology as science of behavior
Para behaviorism ; bagaimana dg nature vs nurture
Menurut Weiten (2004) psikologi mrpk proses fisiologi
dan kognisi
Dhabhar & McEwen (2001) stimuli
stress perception
seterusnya menimbulkan stress response
PSIKOLOGI
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Ilmu yg mempelajari ttg perilaku
– Overt
– Covert
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Classical Pavlovian conditioning mrpk suatu learning
process dlm membentuk kognisi
Menurut Ader (1964) learning process dpt
menentukan koping individu
Skinner (behaviorism) individu tdk akan mengulang
aktivitas yg merugikan
Sigmund Freud (1856-1939) ; konsep unconcious
mrpk determinan penting dlm dr behavior
Watson’s behaviorism yaitu pemikiran ttg stimulus –
response realtionship.
Dhabhar & McEwen yg menghubungkan konsep
Lindermann – Caplan & Hans Selye
NEUROTRANSMITER
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Suatu sinyal kimia yg mampu berperan sbg alat
komunikasi sel
Melalui gap junctions membentuk hubungan sitoplasma
antar sel yg berdekatan
Parakrin disekresi oleh sel dan berdifusi ke sel
didekatnya
Autokrin berefek pd sel yang mensekresi
Endokrin ad hormon yg masuk kedalam darah dan
hanya utk sel target yg mempunyai reseptor spesifik
Sinyal listrik pd neuron mengakibatkan lepas
neurotransmiter yg berdifusi mlli celah kecil ke sel
target
Neuron melepaskan neurohormon dan hanya sel yg
memiliki reseptor yg memberikan respon
SINAPS DAN NEUROTRANSMITER
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Sinaps ad titik temu antara neuron dan sel target
Setiap sinaps terdiri dari 3 bagian ;
 terminal akson presinaptik
 synaptic cleft (celah antar sel)
 membran sel postsinaptik
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Berdasarkan efeknya thdp potensial membran
neuron postsinaptik dibagi atas ;
– Excitatory synapse
– Inhibitory synapse
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Berdasarkan stimulusnya, sinap dibagi atas ;
o Electrical synapse
o Chemical synapse
Klasifikasi Neurotrsnmiter :
 molekul kecil, transmiter cepat spt :
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acetylcholine,
amines, amino acids & NO
molekul besar, hampir semua polipeptida yg
umumnya aktif sbg hormon
Acetylcholine disebut cholinergic
Amines : dopamin, norepinephrine, epinephrine,
serotonin, histamin.
Amino acids : glutamate, aspartate (eksitasi) dan
glycine, GABA (inhibisi)
Gases : NO, CO
Purines : adenosine, AMP, ATP
Lipid : anandamide
Polypeptide : Substance P, enkephalin dan endorphin
SISTEM SARAF OTONUM
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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 parasimpatis
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Serat saraf mensekresi :
 serat cholinergic
 serat adrenergic
acetylcholine
norepinephrine
SISTIM LIMBIK
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Merupakan regio paling primitif cerebrum
Terdiri atas :
 Amygdala
 Hyppocampus
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emosi & memori
learning process &
memori
Berperan sbg penghubung antara fungsi
kognitif (reasoning) dan respon emosi spt rasa
takut dll
Cortex Cerebri mempunyai 3 area :
 area sensori
 area motorik
 area asosiasi
persepsi
pergerakan
mengintegrasi informasi dan
tingkah laku
IMUNOLOGI
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Ilmu yg mempelajari ttg ketahanan tubuh
Terdiri atas :
• Innate immunity
• Adaptif immunity
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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.
Imunitas tubuh dapat di modulasi
SKEMATIK UMUM INTERAKSI SISTEM
SARAF DAN SISTEM IMUN
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General schematic of the
interactions between the
nervous system and the
immune system mediated
primarily by soluble, secreted
products of cells in each
system.
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The prevailing view is that
these two complex systems
interact and share in the effort
of promoting organismic
homeostasis by the use of
mediators produced in each
system.
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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.
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This circuit is viewed as a
bidirectional response
system in which the immune
system responds to
noncognitive stimuli, such
as infectious agents, and
signals the nervous system,
which responds to cognitive
stimuli such as
neurochemicals, cytokines,
and physical and emotional
stimuli and, in turn, signals
the immune system.
NEUROMODULASI PADA SISTEM SARAF
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Noradrenergic fibers from the
spinal ganglia enter the spleen
through the trabecular
meshwork, distribute around
and innervate areas of
accumulated lymphocytes
called the white pulp and the
periarteriolar lymphatic
sheaths, which consist of dense
aggregates of lymphocytes.
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During antigenic stimulation,
there is increased production
of norepinephrine, substance
P, somatostatin, and vasoactive
intestinal peptide, which
regulates blood flow and
lymphatic activation.
AKTIVITAS NORADRENERGIK
PADA MAKROFAG (APC)
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Antigen presentation by
macrophages and the lymphocyte
response are modulated by
noradrenergic activity.
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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.
AKTIVITAS DI PEMBULUH DARAH
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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.
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Once receptor–ligand
binding occurs, the
lymphocytes can migrate
from the blood vessel into
the tissues
ACTH DAN GLUKOKORTIKOIDS
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Adrenocorticotropic hormone
(ACTH) produced in the
pituitary gland stimulates the
production of glucocorticoids
by the adrenal glands (A).
These naturally occurring
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
evidence that lymphocytes can
produce biologically active
neurohormones such as ACTH
and thus may serve as an
alternative source of such
mediators
ACTH MENEKAN Ab
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ACTH suppresses
antibody production
in vitro. The hormone
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
Production of cytokines by cells in the
immune system (A) and nervous system (B).
Peran molekul MHC
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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,
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.
KOMUNIKASI DUA ARAH
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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.
HPA-AXIS
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Some neuroendocrine
pathways to the
immune system. Many
of the hormones
released by the
hypothalamus,
pituitary and endocrine
glands affect the
activity of
lymphocytes.
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In stress, hormones
and neurotransmitters
from the adrenal
cortex (corticosteroids)
and medulla
(principally
catecholamines and
enkephalins) are
especially important.
SISTEM SARAF DAN SISTEM IMUN
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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.
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In addition, lymphocytes
and other immune cells
release some
neurotransmitters and
neurohormones.
RANGKUMAN
PSIKONEUROIMUNOLOGI
EFEK STRESOR TERHADAP IMUNITAS
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Tingkat stres merambatkan sinyal ke HPA axis yg
akhirnya sampai ke sel imun.
Konsep triple S (stress signaling substances) mrpk alat
komunikasi antar sel saat sel mengalami stres.
Sinyal tsb ad :
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Corticotropin releasing hormone (CRH)
Arginine vasopressine (AVP)
Proopiomelanocortine (POMC)
Proenkephaline (PENK)
Prodynorphine
Adenocorticotropine hormon (ACTH)
Epinephrine
Nor-epinephrine
Glucocorticoid meliputi semua neurohormonal
Sitokin
Reseptor / ligand
GLUKOKORTIKOID
Dihasilkan oleh kelenjar adrenal
Menginduksi apoptosis
Menginaktivasi NF-B yg mrpk promoter sitokin
 Menghambat transkripsi gen IL-2
 Pemicu downregulation ekspresi MHC II
 Menekan produksi IL-2 & IFN-γ
 Meningkatkan produksi IL-4
 Bekerja sama dg hormon stres lain spt
katekolamin
 Efek stresor ekhausted dpt menurunkan imunitas
baik alami maupun didapat.
 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 :
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Kerentanan individu terhadap infeksi oleh karena
kemampuan koping
Koping sangat berkaitan dengan learning process
PNI & INFLAMASI
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Inflamasi mrpk respon jaringan vaskuler terhadap
patogen
Inflamasi yg berhasil akan diakhir dg proses
penyembuhan
Inflamasi mrpk satu diantara 4 bentuk imunitas alami
Semua stimuli yg membangun stress perception dapat
menurunkan imunitas, shg meningkatkan kerentanan
terhadap infeksi
Kualitas stress perception menghasilkan kognisi dan
bentuk koping individu yg dapat memodulasi sistem
imun.
Inflamasi terjadi krn keluarnya mediator spt bradikinin,
histamin & serotonin akibat learning process.
ARMADILLO DAN MANUSIA
HOSPES Mycobacterium leprae
PSIKONEUROIMUNOLOGI KUSTA
DAPAT DIPELAJARI DIHARI LAIN