MEKANISME PENYAKIT INFEKSI

DALAM KONTEKSNYA DENGAN

PSIKONEUROIMUNOLOGI
 PENDAHULUAN
 Psikoneuroimunologi neologism
 Psiko psikologi
 Neuro neurologi
 Imunologi
 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
 Stres mempunyai 3 tahapan :
 Activation
 Resistance
 Exhaustion
 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
 Ilmu yg mempelajari ttg perilaku
 Overt
 Covert
 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
 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
 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

 Berdasarkan efeknya thdp potensial membran neuron

postsinaptik dibagi atas ;
 Excitatory synapse
 Inhibitory synapse
 Berdasarkan stimulusnya, sinap dibagi atas ;
o Electrical synapse
o Chemical synapse
 Klasifikasi Neurotrsnmiter :
 molekul kecil, transmiter cepat spt : 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
 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
 Serat saraf mensekresi :
 serat cholinergic acetylcholine
 serat adrenergic norepinephrine
 SISTIM LIMBIK
 Merupakan regio paling primitif cerebrum
 Terdiri atas :
 Amygdala emosi & memori
 Hyppocampus learning process &
memori
 Berperan sbg penghubung antara fungsi kognitif
(reasoning) dan respon emosi spt rasa takut dll
 Cortex Cerebri mempunyai 3 area :
 area sensori persepsi
 area motorik pergerakan
 area asosiasi mengintegrasi informasi dan
tingkah laku
 IMUNOLOGI
 Ilmu yg mempelajari ttg ketahanan tubuh
 Terdiri atas :
• Innate immunity
• Adaptif 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.
 Imunitas tubuh dapat di modulasi
 SKEMATIK UMUM INTERAKSI SISTEM
SARAF DAN SISTEM IMUN
  General schematic of the
interactions between the
nervous system and the
immune system mediated
primarily by soluble, secreted
products of cells in each
system.
 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.
 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

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
 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.

 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)
 Antigen presentation by
macrophages and the lymphocyte
response are modulated by
noradrenergic activity.

 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
 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
binding occurs, the
lymphocytes can migrate
from the blood vessel into
the tissues
ACTH DAN GLUKOKORTIKOIDS
 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
 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
 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
 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
 Some neuroendocrine
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
and neurotransmitters
from the adrenal
cortex (corticosteroids)
and medulla
(principally
catecholamines and
enkephalins) are
especially important.
SISTEM SARAF DAN SISTEM IMUN
 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
and other immune cells
release some
neurotransmitters and
neurohormones.
RANGKUMAN
PSIKONEUROIMUNOLOGI
EFEK STRESOR TERHADAP IMUNITAS
 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 :
 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
 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
kemampuan koping
 Koping sangat berkaitan dengan learning process
 PNI & INFLAMASI
 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