MEKANISME PENYAKIT INFEKSI DALAM KONTEKSNYA DENGAN PSIKONEUROIMUNOLOGI Oleh : Joni Haryanto

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 ; Electrical synapse Chemical synapse

Klasifikasi Neurotrsnmiter : 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 Terima Kasih