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IMUNOLOGI :

SISTEM IMUN SELULAR


HARIYANTO IH., M.SI., APT. (hariyanto.ishak@pharm
.untan.ac.id)
PHARMACY STUDY
PROGRAMME
FACULTY OF MEDICINE
UNIVERSITY OF
TANJUNGPURA
2015/2016

PENDAHULUA
N
SISTEM IMUNI
PERTAHANAN
TUBUH

FUNGSI SISTEM
IMUN
Pengenalan (selfnonself)
1.
2.

Efektor (mengeliminasi)

Regulasi
(keseimbangan)
3.
4.

Memori (re-infeksi)

SISTE IMU
M
N
Immune

System

Adaptive
(Specific)
20 line of defense

Innate
(Nons
pecific)
1 line
of defense

Humoral

Physical

Barrier

Prolects.!re-e)(posure

COl t 4IOnents

Cellular

COli4JOnents

HumoraJ

COl '4X>nents

http://people.eku.edu/ritchisong/301notes4b.ht
ml
fVJa+>!NO
(~/losporlSiJ)

m~

_--.
BccI

F.uwcdon .. prateln classes In the

co..........ent~l.m

Binding to antlg_n;antlbody and


pathog_n surlaces

COn1p.....

Clq

Binding to rnannose onba~a

MeL

Activating

Clr
Cls
C2~

enzymes

Bb

SISTEM

Membrane-binding

.,.-oulns and

opsonlns

PeptIde_"lIlton

KOMPLEME

(humor innat
N
al
e)

ofl"' ........ lon


Me",br~ ne-atho proteins

0
MASPOIb
2.
Ob

00
CSb

C6
I

Co1'nplernent receptors

C7
C8
C9

CRl
CR2
CR3

C-ornpel rnent-regulatocy proteins

CR4
C1qR
C11NH

C4bp
eft 1

ao .. ", .. ow
.
pluri ....

_ ..........
c. @..
.

m~.lo;d

NK

ITMItur.

Imrnatu",.

dendritic

de-ndrhic cell

c.
u

Garland Scl~nce 2008)

Sistim Irrrurt

Sel-Sel
-g'"

1.
2.

S'istern Irnun Bawaan


Sel F agositik ????
'-

0')0

http://pathmicro.med.sc.edu/ghaffar/innate.htm

Innate/Bawaan

Adaptive/Dapatan

Nonspec~icIm
mun~y

Spe Immun
cffic ~y

Response is
antigenThere
is immediate
independent
maximal response
Not
antigenExposure
resuts in
specific

mem

Response is
antigeri-dependent
There is time between
maxi
a lag
exposure and
maJ
response
Antigenspecnic
Expo results in
mem

PAMPs, PRRs
http://lpi.oregonstate.edu/mic/micronutrients-health/immunity
pathogen-asscx::iated

molecular

pattern

_/bacterium

recognition

phagosome

.....-

receptor

phagolysosome

..
Macrophage

matory cytoktnes

MOLEKUL-MOLEKUL
PERMUKAAN

Ligan vs Reseptor

PAMP (Pathogen-Associated Molecular Pattern)


Patogen
PRR (Pattern-Recognition
innate immunit cell
Receptor)
y

TLR (Toll Like Receptor)

CD (Cluster of differentiation)

MHC (I dan II)

Reseptor (TCR / BCR, dll)

Co-stimulatory molecule

Toil-like
receptor

by
Inn.e Immune
recolnltlon
Toil-like receptors
Llglnd

TLR-l
:TLR-2

heterodim
TLRer

2:TLR-6

heterodim
er
TLR-4

dimer
(plus
MO2
. and C014)
TLRS

Peptidoglycan
lipoproteins
lipoarablnomann (mycobacteri
a)
an
GPI (T. cruzi)
Zymosan
dsRN
(yeast)
A
lPS (Gramnegative
bacteria)
lipoteichoic acids
(Gram-positive
Flagelli
bacteria)
n
ssRN
A

TLR8
i

TLR-9

Grich
oligonucleotides
Unmethylat
ed

diacyl
trlacyl
lipopeptid lipopeptid flagelli
n
es
es
TLR- nR6
2

TLR- TLR- nR
1
2
S

dsRN
A
Endosom
e

LP
S

nR
4

TLR9

Th...

acro

for ... n~

receptor

mannose

rec.ptON

et

coMtI ....

_,/--""""-

nb

(CD14)

PS re<eptor
TLR-4

FAGOSITOS
IS

glucan
receptor

......
InI .....

bind

scavenger
receptor

to m_'

the r

of

nd ....

.. .

c'JIOl

ion

dn

.eor. of IntI

Macroph

dleto which 'MY bind


ng

.....

bactwle

phagol'ysosome
Flgur.2-8

Immunoblologv. 7ctd. (CCI Garland Sc14tl'lc2. 008)

11

PHASES OF PHAGOCYT
http://mad-physio.blogspot.co.id/2010/07/what-is-infection-physical-barrie
OSIS
rs-and.html

Chemotaxis and

adherence
of microbe to phagocyte.

oe

Ingestion of
Formation of a

microbe
phagosome.
by phagocyte.

o
o

Fusion 01the

Digestion of
ingested
phagosome
by to form 8
with microbe
8 lysosome
enzymes.
phagolysosome.
Formation of reslduel
body
containing
Indigestible material.

o
Phagocyt
e

Discharge of

SITOKIN,
KEMOKIN

aad.rl
trigg ...
macropha
.. to
a
releas
cytokina an
g

chemoldn
s
es

DAN
RESPON
Vasodilation an

increase vascula
d
permeabilit
d
r caus
e
y
heat,
and
redness,

swelling

protein

-,

che

mokines

Figure 1-8 Immunobiology, 7ed. (<I) Garland Science

INFLAMA
SI
Inflammator,
releasin
inflammator
mediator
that
g cells
y
migrate
into
tissue,
s cause
pain
n. eutrophil

SITOKIN DAN
KEMOKIN
SITOKIN PROTEIN KECIL TERLARUT YANG MEREGULASI FUNGSI IMUN SELULER,
INFLAMASI

YANG DISEKRESIKAN
DIHASILKAN
RESPON
TERHADAP
STIMULUS
IMUNLAIN
OLEHSEBAGAI
SEL-SEL IMUN
TERTENTU
DAN MEMILIKI
EFEK SISTEM
PADA SEL-SEL

SITOKIN

MENGIKAT RESEPTOR SPESIFIK, KEMUDIAN MEMBAWA SINYAL


MESSENGER
MELALUI
2ndMEGUBAH AKTIVITAS SEL YANG
UNTUK
SITOKIN
DIPENGARUHI
KEMOKIN PROTEIN KECIL TERLARUT, YANG BERPERAN SEBAGAI
KEMOATRAKTAN

FAGOSIT DAN SEL T

KERUSAKAN SEL/JARINGAN AKIBAT INFEKSI BAKTERI, VIRUS DAN LUKA


MENYEBABKAN

HUBUNGAN SISTEM IMUN


BAWAAN dan
IMUN DAPATAN

Sist. Imun bawaan diperlukan untuk


mengaktifkan sistem imun dapatan (vice
versa)

Sist. imun bawaan juga membantu imun


dapatan mengeliminasi patogen (vice
versa)

FUNGI SEL IMUN


BAWAAN
Sebagai APC (Antigen Presenting Cell) cth:
Sel

dendritik dan Makrofaga (MHC I dan MHC II)

Eliminasi (Efektor) Sel dendritik, makrofaga, NK


Cell

APC
Setelah mengenali suatu
antigen, APC akan
masuk ke saluran
limfatik dan terbawa ke
arah nodus-nodus
limfe
terdekat
untuk
dan
bertemu
mengaktivasi T
sel
.
CX;P.5 ligand
Type1
IFN-y
IFN-o
IL-18

PAMPalTFs

TH1-polanzmg

faaortIL-1

2.

L27)

IFN-l"
TNF-P

IL-t
IL-5

IL-~3

CCR2 ligand

Type2
hislafnine
PAMPsfTFs
PGE2
TSLP
"--10
TGF-f

TH2-po!Arizlng
tack)( (CCL2)

Regu'aIXXy

PAMPs,'TFs
Tr~polari2lng
faaor (IL-10. TGF-jJ)

L-10

TGF-{J

Sel terinfeksi

pCTL.

SelThz

IL-2

I'-.
~

IL-4,

IIFN Y
TNF ...

Se ITS i~otoksik efektor

Gall1bal~ IT.1 Interaksi

_;;.

_-6, 'L- ~O
TOF-8

SeITh~

Produksi
Arrtibo di

sistern rmun dapat an dan


2003)

Sel B memori

bawaan

(Burmester

dan Pezzutto,

Cellular
Innate Immunity

2
Cellular
Adaptive Immunity

Gerd-Rudiger Burmester and Antonio Pezzutto (2003) : Color Atlas of Immunology; Thieme; Stuttgart; p

Adherence toeplth.llum

Local inf_tion,
p .... tration

Local infection of tis .....

AaptIY.

Imlnuntt,

of
L

...,. '

_-

"_

-.

-r-: .. _ ..

-c-

':::- -

. 1 1

~_, - "
~

tissue

--.
_

.. _': ".
.

.~, -

' .

epithelium

'
"

-,.
-.

.~

tis

W
sue

~~.'.g;

.. ' (Q)

'--~rR\
~--{q

~~

Protection ... Inst Infection

Normal flora
Local chemical factors
Phagocytes
(especially in lung)

Figure 2-6 Immunobiology, led. (<eJ

Wound healing induced


Antimicrobial proteins
peptides, phagocytes,
and
and
complement destroy
invading microorganisms
Activation of 1:"3T cells?
Science 2008',

Complement, cytokines,
chemoklnes, Phagocytes,
NK cells

Activation of macrophages
Dendritic cells migrate to
lymph nodes to initiate
adaptive immunity
Blood clotting helps limit
spread of Infection

Infection cleared by specific


antibody, T-cell dependent
macrophage activation
and cytotoxic T cells

Sel B

Sel B yang telah dibentuk oleh sumsum tulang belakang


belum aktif . Saat ada patogen, sel B diaktifkan melalui 2
cara yaitu T cell dependent activation dan T cell
independent activation
Sel Th yang aktif akan merangsang sel B
berproliferasi dan berdiferensiasi menjadi sel plasma
yang mensekresi antibodi

Cellular
Adaptive Immunity

Sel T

Humoral
Adaptive Immunity

Imunoglo
bulin

Sel T membantu proliferasi sel B untuk menjadi sel


plasma sehingga dihasilkan Ig dengan pelepasan
sitokin (IL-4, IL-5, IL-6).

Cellular
Innate Immunity
Humoral
Adaptive Immunity

Ig

Destruksi
antigen
disebut
Reseptor
terikat
antibodyFc di sel
dependent
Ag
NK
cell
mediated
cytotoxicity
Sel NK mengekspresikan reseptor FcRIII (CD16) yang mengenali
IgG1
(ADCC)

dan IgG3. Mekanisme penyerangan mirip dengan Tc, yaitu melepaskan


granul sitoplasmik berisi perforin dan granzyme.

Sel t regulator

RESPON TERHADAP INFEKSI


AWAL
Innate
Immunity
(immediate

Recognition

Infecti
on

bY
prlformad,

Earl,
induced
0-4 hours)

ReMoval
of infectious
agent

"

non:.
Recognition

..

Inflammatio
n
.

~dficof and
innate
1
)
broadl,
recruitment
iaobial..assodat
response (.arly:
and
ed specific
molecular
4-96 hours)
,effectors
activa,ion of
patterns
Adaptive
Transport
Rlcqgniti
effector
cells
.
.>
.
immune
of
on by
l'
}
.A
Inf~ctio
naive
_tigen
to
1
response
8 andT
n
lymphoid
figure 2-' Immunobiology, 7ed. ( Garland cells
Uate: >96
organs

Infecti
On

1
1

.
)I

Removal
ef
infectious
agent
Clonal
expansion

and
differentiation
to effector

}
}

Removal
of
- infectious
agent

--'

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