Patogenesis-2

8/9/2019 Patogenesis-2

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Viral Pathogenesis


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Viral Pathogenesis

Viral pathogenesis is the process by which a viral infection

leads to disease.

Viral pathogenesis is an abnormal situation of no value tothe virus.

The majority of viral infections are subclinical. It is not in

the interest of the virus to severely harm or kill the host.

The consequences of viral infections depend on theinterplay between a number of viral and host factors.


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PATOGENESIS PENYAKIT VIRUS

PRINSIP : Terjadi siklus replikasi virus dalam sel hospesRespon imunseluler SitopatologiKematian, hiperplasia, kanker, tidak

terjadi apa-apa

Infeksi Viruspenyakit virusabnormalitas struktur!fungsi"

#Subklinik : infeksi dengan gejala tidak nyata#Klinik : infeksi dengan gejala $ tanda

Virus patogenmampu menginfeksi $ menyebabkan penyakit

Strain virulen strain yang lebih sering menyebabkan penyakit dibandingkan

strain lain

EFEK SITOPATIK (ESP)VIRUS SEL HOSPES PEKA


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utcome of Viral Infection

Acute Infection

! "ecovery with no residue effects

! "ecovery with residue effects e.g. acute viral encephalitis leading to

neurological sequelae.! #eath

! Proceed to chronic infection

Chronic Infection

! $ilent subclinical infection for life e.g. %&V' ()V

! * long silent period before disease e.g. +IV' $$P(' P&,

! "eactivation to cause acute disease e.g. herpes and shingles.

! %hronic disease with relapses and e-cerbations e.g. +)V' +%V.

! %ancers e.g. ()V' +T,V/' +PV' +)V' +%V' ++V0


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1actors in Viral Pathogenesis (ffects of viral infection on cells 2%ellular

Pathogenesis3

(ntry into the +ost

%ourse of Infection 2Primary "eplication' $ystemic

$pread' $econdary "eplication3

%ell4Tissue Tropism

%ell4Tissue #amage

+ost Immune "esponse

Virus %learance or Persistence


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%ellular Pathogenesis

%ells can respond to viral infections in 5 ways6 2/3 7o apparent change'283 #eath' and 253 Transformation

#irect cell damage and death from viral infection may result from

! diversion of the cell9s energy! shutoff of cell macromolecular synthesis

! competition of viral m"7* for cellular ribosomes

! competition of viral promoters and transcriptional enhancers for cellulartranscriptional factors such as "7* polymerases' and inhibition of theinterferon defense mechanisms.

Indirect cell damage can result from! integration of the viral genome

! induction of mutations in the host genome

! inflammation

! host immune response.


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REPRODUKSI VIRUS DALAMBIAKAN SEL :

# Adanya ESP Polioy!li"i#$Va%i&!lla$ H!%'!# Si'l!$ H!%'!#oo#"!%$ Mo%*ili$ M+'#$In,l+!n-a$ D!n.+!$ E&/o0i%+#$

1o#a&2i!0i%+#$ 1y"o!.alo0i%+## Adanya /a*a"an !"a*oli#!

#!l Polioy!li"i#$ E&/o0i%+#$Ad!no0i%+# 1o#a&2i!0i%+#

# Adanya '!*!n"+2an/!a.l+"inin Vi%+# In,l+!n-a$Pa%o"i"i# !'id!i&a$ E&/o0i%+#$1o#a&2i!0i%+#

# Adanya '%o#!# /!ad#o%'#iVi%+# Pa%ain,l+!n-a

# Adanya '!%+*a/an o%,olo.i2 #!lVi%+# Sa%&oa Ro+#$ Siian

Vi%+# 34 (SV 34)

ESP (1YTOPATHI1 EFFE1T) :

# P!n..!*+n.an #'" *alon# Pla#oli#i## Pi2no#i## Ka%yo%!2#i## P!*!n"+2an #in#i"i+# P!*!n"+2an #!l %a2#a#a *!%in"i

*anya2 (M+l"in+&l!a"!d Gian" 1!llFo%a"ion)

# Va2+oli#a#i5P!*!n"+2an #!l *+#a

(Foay 1!ll Fo%a"ion)# N!2%o#i#5'!n.!%+"an# P!*!n"+2an *adan in2l+#i

(In&l+#ion Body Fo%a"ion)


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TIPE ESP PADA SEL HOSPES

Bia2an S!l No%al Vi%+#

P!n..!*+n.an

Pla#oli#i#

Va2+oli#a#i5S!l *+#a

Pi2no#i#

Sin#i"i+5S!l %a2#a#a

Badan In2l+#i

Ka%yo%!2#i#

N!2%o#i#5!n.!%+"


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Viral (ntry

Skin &ost viruses which infect via the skin require a breach in thephysical integrity of this effective barrier' e.g. cuts or abrasions. &anyviruses employ vectors' e.g. ticks' mosquitos or vampire bats to breachthe barrier.

Conjunctiva and other mucous membranes rather e-posed site andrelatively unprotected

Respiratory tract In contrast to skin' the respiratory tract and all othermucosal surfaces possess sophisticated immune defence mechanisms' aswell as nonspecific inhibitory mechanisms 2cilliated epithelium' mucussecretion' lower temperature3 which viruses must overcome.

Gastrointestinal tract a hostile environment: gastric acid' bile salts'etc. Viruses that spread by the ;I tract must be adapted to this hostileenvironment.

Genitourinary tract relatively less hostile than the above' but lessfrequently e-posed to e-traneous viruses 2


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JALUR ASU! "IRUS #A$A #%RU!AA& 'U(U)


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6ALUR UMUM INFEKSI VIRUS

6al+% Ma#+2 K!lo'o2 Vi%+# G!7ala lo2al 'ada "!'a" a#+2In,!2#i !ny!l+%+/ dan'!nya2i" o%.an 2/+#+#

Sal+%an P!%na'a#an Ad!no0i%+#

H!%'!#0i%+#

Po0i%+#

Pi2o%na0i%+#

To.a0i%+#

O%"iyo0i%+#

Pa%ayo0i%+#

1o%ona0i%+#

K!*anya2an S'!#i!#

E'#"!in Ba%%$H!%'!# #i'l!

8

Rino0i%+#

8

In,l+!n-a

Pa%ain,l+!n-a$ 0i%+# Sin#i"ial

'!%na'a#an

K!*anya2 S'!#i!#

8

Va%i&!lla

1a&a% ('+na/)

B!*!%a'a En"!%o0i%+#

R+*!la

8

Gondon.$ 1a'a2

8

M+l+" dan Sal+%an U#+# Ad!no0i%+#

H!%'!#0i%+#

Pi2o%na0i%+#

R!o0i%+#

B!*!%a'a #'!#i!#

E'#"!in Ba%%$H!%'!#i'l!

8

Ro"a0i%+#

8

1y"o!.alo0i%+#

B*%' En"!%o0i%+#$ Polio dan

H!'a"i"i# A

8

K+li"

L+2a %in.an

T+#+2an

Gi.i"an

Pa'o0a0i%+#

H!%'!#0i%+#

Po0i%+#H!%'!# 0i%+#

H!'adna0i%+#

R!"%o0i%+#

Ra*do0i%+#

To.a0i%+#

Fla0i0i%+#

Pa'iloa0i%+#

H!%'!# Si'l!

Mol+#&+ &on"a.io#+$O%,

8

8

8

8

8

8

8

8

8E'#"!in Ba%%$ 1y"o!.alo0i%+#

H!'a"i"i# B

AIDS

Ra*i!#

Banya2 #'!#i!# EEE

Banya2 #'!#i!# d!a 2+nin.


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UNTUK MENYEBABKAN PENYAKIT VIRUS HARUS :Ma#+2 R!'li2a#i '%i!% P!ny!*a%an Vi%+# 1!d!%a #!l R!#'on i+n Inan.

P!*!%#i/an Vi%+#5in,!2#i !n!"a' #!&a%a '!%#i#"!n P!l!'a#an Vi%+#

INFEKSI VIRUS :# Kon"a2 lan.#+n.# Kon"a2 "a2 lan.#+n.

BAGANPOLA PATOGENESIS POTENSIAL INFEKSI VIRUS

In,!2#i 0i%+# '%i!%

T!'a" lo2ali#a#i

Vi%+#

P!nya2i" 'd "!'a"

lo2ali#a#i5a#i'"oa"i2

P!ny!*a%an lan.#+n.

'd 9"a%.!" o%.an#N!%0+# '!%i,!%

Da%a/Si#"i li,a"i2Ta%.!" o%.an

Li'a

Ha"i

L!2o#i"P!nya2i"

P!nya2i"

Da%a/


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PATOGENESIS

P!a#+2an ; R!'li2a#i P%i!%P!ny!*a%an 0i%+# ; "%o'i#! #!l

# 0i%+# !ny!*a*2an '!nya2i" 'ada "!'a" yan. 7a+/ da%i "!'a"

a#+2nya# 0i%+# !'+nyai "%o'i#! "!%/ada' 7a%in.an a"a+ #!l

R%S%&T'R2/+#+# di'!%+2aan #!l +n"+2 0i%+# (%!#!'"o%2o'on!n '!%+2aan yan. *!%in"!%a2#i #!&a%a 2/+#+# d!n.an

#+a"+ da!%a/ di'!%+2aan 0i%+# (2a'#id5#!l+*+n.) +n"+2

!+lai in,!2#i)

M!li*a"2an ENIM


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1!d!%a #!l dan P!nya2i" 2lini2In,!2#i 0i%+# 2!%+#a2an #!l57a%in.an$ i#alnya : /ilan.nya

'%od+2#i /o%onE'i"!l +#+# &!'a" %!.!n!%a#i

O"a2 la*a" %!.!n!%a#i

P!ny!*+/an

a2i2a" in,!2#i 0i%+# *i#a "!%7adi 2!a"ian a"a+ #!*+/ !li*a"2ani+ni"a# /+o%al *!%'!%an"a%a #!l$ in"!%,!%on$ li,o2in dan ,a2"o%

'!%"a/anan lain

P!l!'a#an 0i%+#*anya2 "!%7adi 'ada "!'a" a#+2 0i%+#

Vi%+# Ra*i!# "ida2 !n.alai '!l!'a#an ,a"al


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KEMUNGKINAN YANG DAPAT TER6ADI PADA INTERAKSI VIRUS < HOSPES

#Resistentak terlihat terjadi adanya hubungan

#Infeksi Subklinik&enyembuhan Infeksi &ersisten

#&enyakit (kut!KlinikKematian

Sembuh dengan!Tanpa se)uele

Sembuh dengan Infeksi *atent!&ersisten

#Infeksi +enahun Khronik"(simptomatik, *atent

*atent dengan Rekurensi

&ersisten dengan &enyakit Khronik

nfeksi Virus *ambat Slo Virus Infetion"

#Transformasi +alignan

#Virus bertindak sebagai .Triger/Reaksi 0ospes tak normal Sindrom

Reye, Sindrom 1remik 0emolitik


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%ourse of Viral Infection

#rimary Replication

! The place of primary replication is where the virus replicates after

gaining initial entry into the host.

! This frequently determines whether the infection will be locali=ed atthe site of entry or spread to become a systemic infection.

Systemic Spread

! *part from direct celltocell contact' the virus may spread

via the blood stream and the %7$.

Secondary Replication

! $econdary replication takes place at susceptible organs4tissues

following systemic spread.


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%ell Tropism

Viral affinity for specific body tissues 2tropism3 is

determined by

! %ell receptors for virus.

! %ell transcription factors that recogni=e viralpromoters and enhancer sequences.

! *bility of the cell to support virus replication.

! Physical barriers.

! ,ocal temperature' p+' and o-ygen tensionen=ymes and nonspecific factors in bodysecretions.

! #igestive en=ymes and bile in the gastrointestinaltract that may inactivate some viruses.


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%ell #amage

Viruses may replicate widely throughout the body without

any disease symptoms if they do not cause significant cell

damage or death.

"etroviruses do not generally cause cell death' being

released from the cell by budding rather than by cell lysis'

and cause persistent infections.

%onversely' Picornaviruses cause lysis and death of the

cells in which they replicate' leading to fever and increasedmucus secretion in the case of "hinoviruses' paralysis or

death 2usually due to respiratory failure3 for Poliovirus.


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Immune "esponse

The immune response to the virus probably has the greatest impact

on the outcome of infection.

In the most cases' the virus is cleared completely from the body

and results in complete recovery.

In other infections' the immune response is unable to clear the

virus completely and the virus persists.

In a number of infections' the immune response plays a major

pathological role in the disease.

In general' cellular immunity plays the major role in clearing virus

infection whereas humoral immunity protects against reinfection.


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Immune Pathological "esponse

(nhanced viral injury could be due to one or a mi-ture of

the following mechanisms:

! Increased secondary response to Tc cells e.g. +)V! $pecific *#%% or complement mediated cell lysis

! )inding of unneutrali=ed virus*b comple-es to cell

surface 1c receptors' and thus increasing the number

of cells infected e.g. #engue haemorrhagic fever' +IV.

! Immune comple- deposition in organs such as the

skin' brain or kidney e.g. rash of rubella and measles.


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Viral %learance or Persistence

The majority of viral infections are cleared but certain

viruses may cause persistent infections. There are 8

types of chronic persistent infections.

True ,atency the virus remains completely latent

following primary infection e.g. +$V' V>V. Its

genome may be integrated into the cellular genome or

e-ists as episomes.

Persistence the virus replicates continuously in the

body at a very low level e.g. +IV' +)V' %&V' ()V.


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&echanisms of Viral Persistence

! antigenic variation

! immune tolerance' causing a reduced response to an antigen' may be dueto genetic factors' prenatal infection' molecular mimicry

! restricted gene e-pression

! downregulation of &+% class I e-pression' resulting in lack ofrecognition of infected cells e.g. *denoviruses

! downregulation of accessory molecules involved in immune recognitione.g. ,1*5 and I%*&/ by ()V.

! infection of immunopriviliged sites within the body e.g. +$V in sensoryganglia in the %7$

! direct infection of the cells of the immune system itself e.g. +erpesviruses' "etroviruses 2+IV3 often resulting in immunosuppression.


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(-amples of Viral Pathogenesis


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+erpes $imple- Virus

+$V is spread by contact' as the virus is shed in saliva' tears' genital

and other secretions.

Primary infection is usually trivial or subclinical in most individuals.

It is a disease mainly of very young children ie. those below ? years.

*bout /@A of the population acquires +$V infection through the

genital route and the risk is concentrated in young adulthood.

1ollowing primary infection' B?A of orally infected individuals and

C@A of patients with genital herpes will e-perience recurrences. The actual frequency of recurrences varies widely between

individuals. The mean number of episodes per year is about /.C.


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Pathogenesis

#uring the primary infection' +$V spreads locally and a shortlived

viraemia occurs' whereby the virus is disseminated in the body. $pread to

the to craniospinal ganglia occurs.

The virus then establishes latency in the craniospinal ganglia.

The e-act mechanism of latency is not known' it may be true latency

where there is no viral replication or viral persistence where there is a low

level of viral replication.

"eactivation * It is well known that many triggers can provoke arecurrence. These include physical or psychological stress' infection:

especially pneumococcal and meningococcal' fever' irradiation: including

sunlight' and menstruation.


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AKTIVASI PERIODIK INFEKSI VIRUS HERPES SIMPLE=

> ? @ 3

A

B

1

D

E

F

G

H

I

6

Ga%i# a*an.In,!2#i ini"ial

S"i+l+#

A 8 6 In,!2#i %!2+%!n

> In,!2#i #+*2lini2 (ina''a%!n") &o0!%"

? In,!2#i 2lini2 (a''a%!n") o0!%"

@ In,!2#i la"!n"

3 In,!2#i 2lini2

In,!2#i la"!n"


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%linical &anifestations

+$V is involved in a variety of clinical manifestations

which includes :

/. *cute gingivostomatitis

8. +erpes ,abialis 2cold sore3

5. cular +erpes

B. +erpes ;enitalis

?. ther forms of cutaneous herpesD. &eningitis

0. (ncephalitis

E. 7eonatal herpes


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GAMBARAN PENYAKIT VIRUS AKUT

INFEKSI LOKAL INFEKSI SISTEMIK

2ontoh penyakitspesifik

&ernapasan Rinovirus" 2ampak

Tempat patologi &intu masukTempat yangberdekatan

*ama inkubasi Relatif pendek Relatif panjang

Viremia Tidak ada (da

*ama imunitas

3ervariasi, mungkin

pendek 3iasanya umur panjang

(b sekretor Ig(" padaresistensi

penting Tidak penting


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VIRUS ONKOGENIK

VIRUS DNA :

PAPOVAVIRIDAEVi%+# PolyoaSiian Vi%+# 34 (SV 34)Vi%+# Pa'iloa K!lin&iVi%+# Pa'iloa Bo0in

HERPESVIRIDAEVi%+# P!nya2i" Ma%!2Vi%+# Ka%#inoa Kodo2 L+&2!H!%'!#0i%+# Saii%iVi%+# E'#"!in 8 Ba%%Vi%+# H!%'!# Si'l!

HEPADNAVIRIDAEVi%+# H!'a"i"i# B

PO=VIRIDAEVi%+# YABAVi%+# Fi*%oa K!lin&i

VIRUS RNA :

RETROVIRIDAEVi%+# L!+2!ia M+%inVi%+# F%i!ndVi%+# Maldn!yVi%+# Ra+#&/!%Vi%+# G%o##

Vi%+# T+o% Maa!Vi%+# AIDS (HTLV III5 LAV$ HIV)

( H+an T


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VIRUS DENGAN REAKSI HOSPES YANG LUAR BIASA

Sind%o R!y! :Vi%+# In,l+!n-aVi%+# Va%i&!lla 8 oo#"!%Vi%+# Pa%ain,l+!n-aP!nya2i" Vi%+# P%odoal yan. "a2 "!%id!n"i,i2a#i R!o0i%+#$ E&/o0i%+#

1o#a&2i!0i%+#$ Ad!no0i%+#$ H!%'!#0i%+#

SINDROM HEMOLITIK :1o#a&2i!0i%+#

Vi%+# 6aninVi%+# E'#"!in 8 Ba%%P!nya2i" Vi%+# P%odoal yan. "a2 "!%id!n"i,i2a#i


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Sind%o G+illain 8 Ba%%! : Vi%+# E'#"!in 8 Ba%%

Vi%+# 0a2#in In,l+!n-a Ba*i Vi%+# Pa%o"i"i# E'id!i&a

En&!,alo'a"i Pa#&a In,!2#i : Vi%+# Mo%*ili Vi%+# Va&&inia Vi%+# Va%i&!lla 8 oo#"!% Vi%+# 'a%o"i"i# E'id!i&a

Mo%*ili A"i'i2 :Vi%+# Mo%*ili 'ada o%an. yan. dii+ni#a#i d!n.an

Vi%+# 0a2#in Mo%*ili yan. dia"i2an


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BAGAN INFEKSI AKUT DAN MA1AM


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INFEKSI VIRUS PADA SALURAN PERNAPASAN

Vi%+# P!ny!*a* yan. Palin. S!%in.

Sind%oa G!7ala U"aa Bayi Ana2


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INFEKSI VIRUS PADA 6ANIN

Vi%+#

ani"a Hail yan. P!2a

A*o%"+#

S'on"an

6anin

No%al

In,!2#i

Anion

In,!2#i

Pla#!n"a

In,!2#i 6anin

In,!2#i Ma"!%nal

T!l+%

6anin

No%al

6anin T!%in,!2#i

(

'!nya2i")

K!a"ian 6anin

(A*o%"+#$ la/i% a"i)Mal,o%a#i

( a"i)

In"%a0

a.in

a Vi%!ia


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INFEKSI VIRUS PERINATAL

K!#!%in.an a2"+ In,!2#i

Vi%+#P%!na"al

(dala +"!%+#)

Na"al

(S!laaP!%#alinan)

Po#"na"al

(S!"!la/P!%#alinan)

In#id!nN!ona"al ('!%

>444 la/i%/id+')

R+*!la 8 6a%an. 4$> 8 4$

1y"o!.alo0i%+# < ?

H!%'!# Si'l! 4$4@ 8 4$

Va%i&!lla


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RESPON IMUN TERHADAP BERBAGAI INFEKSI VIRUS

In"!%,!%on dan I.A P!%"a/anan +"aa 'ada !'i"!l

'!%+2aan

Vi%!ia Vi%+# %!n"an "!%/ada' An"i*odi

Vi%+# di dala #!l Si#"i i+n /+o%al

Si#"i i+n #!l+l!%

An"i*odi !lal+i AD11

P!n./an&+%an 0i%+# di dala #!l M!n.+n"+n.2an

I+no'a"olo.i2


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$ummary

Viral Pathogenesis depends on the comple- interplay of a

large number of viral and host factors.

Viral factors include cell tropism and cellularpathogenesis.

The immune response is the most important host factor' as

it determines whether the virus is cleared or not.

$ometimes' the immune response itself is responsible for

the damage.

Documents

Patogenesis-2