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HUMORAL IMUNERESPON
SUHERMANMagister kedoteran tropis
Universitas sumatera utara
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Adaptive Immunity
Adaptive immune system has two armsAdaptiveImmunity
Humoral Immunity
Cell mediated
Immunity• Provided by B lymphocytes• Can recognize protein
polysaccharide phospholipidand nucleic acid antigens
•
Can act against soluble or!ree antigens
• Provides immunity toe"tracellular bacteria virusesand to"ins
•
Causes #ype I II $ IIIhypersensitivity
• Provided by # lymphocytes• Can recognize only protein
antigens• %ecognizes antigens
presented by APCs withClass I or Class II MHCmolecule
• Provides immunity tointracellular bacteria
viruses !ungi and protozoa• Causes #ype I&
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ariable )( )iversity *( *oining segment o! Ig gene H( Heavy chain +( +ight
B cells
Humoral Immune Response
Maturation, -ntogeny
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Humoral Immune Response
. /a0ve B cells e"press membrane bound immunoglobulin1mIg2
. Mature B cells e"press mIgM and mIg) on their sur!ace
. mIgM acts as antigen receptor called B cell receptor 1BC%2
. 3ach B cell contains 456 BC%s all speci7c !or a singleepitope
. 3ach clone o! B cell is speci7c !or a single epitope
. 458 clones o! B cells can recognize 458 epitopes
B cells
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Humoral Immune Response
. Mature B cells circulate in the blood and lymphand are carried to the secondary lymphoidorgans e9g9 lymph nodes and spleen
. Antigens are also carried by blood or lymph to
the secondary lymphoid organs. B cells usually meet their speci7c antigens in
these organs. An antigen binds to a B cell 1or a clone o! B cells2
which carries mIgM speci7c !or that antigen andactivates it 1clonal selection2
. B cell activated by an antigen starts toproli!erate and increase number o! cells 1clonal
e"pansion2
B cell activation
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Humoral Immune Response
Binding o! a #I antigen with
mIgM on B cellsur!ace
activates the Bcell speci7c !or
it
B cell activation by ! and I B cell anti"ens
Binding o! a #) antigen with mIgM on
B cell sur!ace provides stimulatory
signal 142Antigen is internalized $ presented to
#H cell
C);5 on B cell also bind to C);5+ on #H cell that provides costimulatory
signal 1
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#hymus dependent antigens re=uire B cells to have direct contact with #helper cells in order to !orm antibodies9 #his is how a typical humoralimmune response is carried out in the case o! most antigens9 An APCpresents antigen to a # helper cell the # helper cells can then present
antigen to the B cell and it is activated to produce antibodies9
#hymus independent antigens activate B cells by other mechanisms9 #heycan be bacterial cell wall components like lipopolysaccharides9 #hese arecalled #I>4 Antigens9 -r they can be highly repetitious molecules like theproteins that make up bacterial ?agella9 #hese are #IAntigens9
#I>4 antigens are polyclonal B cell activators meaning they can activate Bcells regardless o! their antigenic speci7city9 @or e"amplelipopolysaccharide is a component o! gram negative bacterial cell walls9 Itcan interact with #+%; on the sur!ace o! B cells9 #he activation o! the B cellby +P binding #+%; produces a diverse collection o! antibodies to beproduced many o! which may interact with the gram negative bacteria9
#I>< antigens activate B cells by linking the membrane boundimmunoglobulin e"pressed on the sur!ace o! the B cell9 #his bypasses theneed !or # cells to activate the B cell to produce antibodies 1But thecytokines released !rom the # cells are use!ul !or proli!eration or to signalimmunoglobulin class switching29
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Humoral Immune ResponseB cell activation by ! and I anti"ens
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Humoral Immune Response
. Plasma cells secrete antibodies
. ecreted antibodies have the same
speci7city as the mIgM on the sur!ace o! Bcell !rom which the plasma cell is derived
. Antibodies are the e:ector molecules o!humoral immune response that bind withthe antigen and eliminate the microbe
. Initially plasma cells secrete IgM antibody
. ithin a !ew days antibody class switchingoccurs and they secrete Ig 1or IgA or Ig32
.
Memory B cells have a long li!e span andprovide heightened immune response i!
the person encounters the same antigen in!uture
Antibody production
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Clonal Selection
Only one type ofantibody—and one
type of B cell—
responds to the
antigenic determinant
That cell type
then produces a
large number of
clones)r9#9&9%ao M)
4<
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Humoral Immune ResponseAnti"en Elimination
Antibodies eliminate antigensby
49 /eutralization o! to"ins andviruses
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Opsonisasi #En$ancedAttac$ment%
AbE Ig Ig3 dan komplemenE CDb C;bmenempelkan 1attach2 antigen ke !agosit !agositosis FF e7sien9
A& Opsonisasi ole$ I"'( )*b( dan )+b,
49 Ig atau IgM dibentuk untuk melawan Agpermukaan 1sur!ace Ag2 organisme atau sel
yg akan di!agositosis @ab dari Ab tersebutbereaksi dgn epitop Ag @c dari I"'berikatan ke neutro7l $ makro!ag menempelkan Ag ke !agosit !agosit akti!
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B
dan sel dendritik untuk meningkatkan !agositosis9
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Opsonisasi #ba.teri .e/a"osit%
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Opsonisasi
4J
Step0- Step01
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Attachment mengawali destruksi Ag9
Mikroorganisme ditempatkan dalam !agosom dicerna lisosom
*ika Ag terlalu besar untuk ditelan,diingestimisalE sel inang yg terin!eksi virus sel
transplant dan sel kanker !agositmengosongkan isi lisosomnya Agdidestruksi ekstraselular9
-psonisasi penting utk melawan
mikroorganisme yg punya struktur anti!agositik1misE kapsul2 Ab yg dibentuk utk melawankapsul dapat menempelkan kapsul ke !agosit9
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Opsonisasi 2a"osit .e Selberu.uran besar
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-psonisasi 1bakteri berkapsul2
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MA) )ytolysis
Ig atau IgM dibentuk utk9 melawan epitopdi membran porsi @ab > Ig atau IgMbereaksi dgn9 epitop tsb9 dan porsi @c > Ab
mengakti!kan 'alur komplemen klasik )3b4567n #membrane attac.
comple89MA)% membuat lubang dalammembran tsb9
a9 Pada bakteri MAC membuat lubang dalammembran terluar 1outer membrane2 $membran sitoplasma dinding sel ram>negati! lisis
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Sitolisis Ba.teri 'ram0Ne"ati/
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b9 Pada virus ber>envelop, MAC merusakenvelop
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c9 Pada sel diri sendiri yg dianggap KasingL selterin!eksi virus sel transplant sel trans!usi
sel kanker
MAC menyebabkan lisis sel direk
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Antibody-Dependent Cellular
Cytotoxicity #A!))% ole$ sel N;el / mempunyai reseptor untuk porsi @c
> Ig9
Bila Ig dibentuk utk melawan epitop disel< KasingL 1misE sel terin!eksi virus selkanker2 porsi @ab N Ab bereaksi dengansel tsb9 sel< / berikatan ke porsi @c N
Ab
sel / melepaskan proteinpembentuk pori,lubang 1per!orin2 enzimproteolitik 1granzyme2 dan chemokine9
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Antibody-Dependent Cellular
Cytotoxicity #A!))% ole$ sel N;ranzyme melewati pori< mengakti!kan
enzime< yg menyebabkan apoptosis selterin!eksi dgn cara merusak struktur
protein sitoskeleton $ degradasi kromosom sel pecah men'adi !ragmen< dibuangoleh !agosit9
Per!orin 'uga dapat menyebabkan lisis sel9el / yang men'alankan A)CC disebut 'uga killer cell
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!estru.si Sel erin/e.si :irus
ole$ Sel N; Melalui A!))
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!estru.si Sel erin/e.si :irus
ole$ Sel N; Melalui A!))
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Netralisasi E.soto.sin3ksotoksin harus berikatan ke reseptor di
sel inang sebelum merusaknya
Ab antitoksin 1umunya Ig2 dibuat utkmelawan protein eksotoksin9
Ab antitoksin bergabung dgn eksotoksinsebelum berinteraksi dengan sel target
1sel inang2 menetralisir toksin9
D5
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Netralisasi E.soto.sin
D4
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Netralisasi :irus&irus harus berikatan 1adsorbsi2 terlebih
dahulu ke reseptor di membran plasma selinang untuk mengin!eksi sel tsb9 $ bereplikasi9
Ab yg dibuat utk melawan epitop< pd9 kapsidatau envelop 1glikoprotein2 virus
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Netralisasi :irus
DD
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Mencegah Adheren Bakteri ke Sel Inang
Bakteri dapat bertahan dari sistem imuninnate dengan memproduksi pili proteinadhesin di dinding selnya dan,atau kapsul
pembentuk bio7lm9Antibodies are made against pili (def)
capsules (def) and adhesins (def) toprevent bacteria !rom adhering to and
colonizing host cells
D;
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Blok Adheren Bakteri oleh Antibodi
D6
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1
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A"lutinasi Mi.roor"anisme
@ungsi utama antibodi yg mempunyaibanyak @ab misalnya pada IgM $ IgA
adalah aglutinasi9Ab tersebut mengabungkan
mikroorganisme< berpadu 1agglutinate2 dikeluarkan dari cairan lim!e dan darah di!agositosis secara e!ekti! olehE Makro!ag mononuklear 1%32
/eutro7l dan sel< !agosit lain
D
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A"lutinasi Mi.roor"anisme
D
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Imobilisasi Ba.teri danProto=oa
@lagela $ cilia memungkinkan m9o9 bergerakmenu'u dan men'auhi sel inang prosestaxis9
Mukosa kandung kemih $ usus secara konstanmembuang bakteri mencegah kolonisasi9
Bakteri motil bergerak sec9 kemotaktik permukaan mukosa kontak dgn9 membran
mukosa menempel membentuk koloni9Ab dapat berikatan ke organ< tsb motilitas
berhenti penyebaran m9o9 terhenti9
DJ
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Humoral Immune ResponseAntibody
. Antibodies are antigen binding proteinspresent on B cell membrane and secreted1immunoglobulins2 by plasma cells
. Membrane>bound antibody con!ers antigenicspeci7city to B cellsG antigen>speci7cproli!eration o! B>cell clone is elicited by theinteraction o! membrane>bound antibody with
its speci7c antigen. ecreted antibodies circulate in the blood
where they serve as the e:ectors o! humoralimmunity by searching and neutralizing
antigens or marking them !or elimination
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Humoral Immune ResponseAntibody Molecule
. Consists o! ; peptide chains• < identical heavy 1H2 chains 1M
65 k)2• < identical light 1+2 chains 1M +combinations
. H>+ combinations are held togetherby disul7de bond between H chains
. Amino acid se=uence in aminoterminal is variable 1 & region2 and!orm the antigen binding site1hypervariable region or C)%2
. Amino acid se=uence in carbo"yl
terminal is relatively constant 1Cregion or @c2 and is responsible !or
M( Molecular weight k)( kilo)alton C)%( Complementaritydetermining region
@c( @ragment crystallizable
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Humoral Immune Response
#here are 6 types o! H chainsE γ, δ, α, µ and ε and 6 domains in H and <domains in + chains
An antibody molecule contains only one type o! H chain and one type o!
+ chain
Antibody
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Humoral Immune Response
. Ig contains γ H chain and is a monomer
Ig has ; subtypes Ig4 Ig
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eosinophils
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Humoral Immune Response
. Primary immune
responseImmune response thatoccurs a!ter 4st e"posureto an antigen
. econdary immuneresponse
Immune response thatoccurs a!ter
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Immunolo"ical
MemoryAntibody iter, The amount of antibody in theserum.
Pattern of Antibody Levels During Infection
Primary Response:
After initial exposure to antigen no antibodies are found in
serum for several days.
A gradual increase in titer first of Ig! and then of Ig" is
observed. !ost # cells become plasma cells but some # cells become
long living memory cells.
"radual decline of antibodies follo$s. )r9#9&9%ao M)
;6
;
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Immunolo"ical Memory#)ontinued%
)r9#9&9%ao M)
;
SecondaryResponse,
Subse>uent e8posure tot$e same anti"en displaysa /aster and more intenseantibody response&
Increased antibodyresponse is due to t$e
e8istence o/ memorycells( ?$ic$ rapidlyproduce plasma cellsupon anti"en stimulation&
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Humoral Immune ResponsePrimary and Secondary Immune Response
Attribute Primary response Secondaryresponse
Antigen type Both # dependentand # independent
-nly # dependent
%esponding cells /a0ve B or # cells Memory B or # cells
+ag period +onger 1;> days2 horter 14> D days2
Peak response -ccurs in > 45 days -ccurs in D> 6 days
Magnitude +ow High 1455> 4555"2
Antibody isotype IgM predominates Ig predominates
Antibody aOnity +ower Higher
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Humoral Immune ResponsePrimary and Secondary Immune Response
Primary immuneresponse
IgM is produced 7rstthen class switch to
Ig
econdary immuneresponse
IgM and Ig are producedsimultaneously !rom the
beginning withpredominant Ig
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Induction o/ Adaptive Immunity
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Induction o/ Adaptive Immunity
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#3%IMA AIH
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)ooperation bet?eenInnate and Adaptive Immunity
. Adaptive immunity is not independent o!innate immunity
. #he phagocytic cells crucial to nonspeci7cimmune responses are intimately involved
in activating the speci7c immune response. &arious soluble !actors produced by a
speci7c immune response have been shown
to augment the activity o! these phagocyticcells
. #hrough the care!ully regulated interplay o!adaptive and innate immunity the two
systems work together to eliminate a
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)ooperation bet?eenInnate and Adaptive Immunity
)omponent Innate Immune System Adaptive Immune System
Macrophages Phagocytosis and killing o!microorganisms
Presentation o! antigens o!phagocytosed organisms to #
lymphocytes A)CC
)endritic cells Phagocytosis and killing o!microorganisms
Presentation o! antigens o!phagocytosed
microorganisms to #lymphocytes
Complements Activation byAlternative or +ectin
pathway
Activation by Classicalpathway
/eutrophils Phagocytosis o! microbes illing o! microbes by A)CC
3osinophils Phagocytosis o! microbes12
illing o! parasites by A)CC
/ cells illing virus in!ected $
cancer cells
illing o! microbes by A)CC
REA;SI
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REA;SIHIPERSENSII:IAS
A)A+AH %3P-M IMU/ QA/ B3%+3BIHA/ )A/ #I)A )II/I/A/ A%3/A )APA# M3/IMBU+A/3%UAA/ *A%I/A/ #UBUH9 -+3H 3++ )A/C--MB )IBAI M3/*A)I ; %3AI
IP
EMANI2ESASI ME;ANISME
I %3AI H3P3%3/I#I@C3PA#
Ig3 dan lg lain
II A/#IB-)I #3%HA)AP 3+ Ig atau IgM
III -MP+3 A/#IB-)I >A/#I3/
Biasanya Ig
I: HIP3%3/I#I&I#A +AMBA# el yang disensitisasi
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REA;SI IPE I)I3BU# *UA %3AI C3PA# %3AI A/A@I+AI A#AU
%3AI A+ A+3%I )I3/A+ 3BAAI %3AI QA/ 33%A #IMBU+ 3U)AH A+3%3/ MAU 3 )A+AM #UBUH9I#I+AH A+3%I QA/ P3%#AMA A+I )IU/AA/ VONPIRGUE PA)A #AHU/ 485 )IA%#IA/ 3BAAI KREA!"IPE#A$U %ANG &ERU&A'L )3/A/ BAHA/ QA/ AMAU/#U 3)UA A+I A#AU +3BIH
)I3BU# *UA %3AI I#-#-I #3%*A)I -+3H A%3/A)IB3/#U A/#IB-)I *3/I Is A#AU IgM #3%HA)AP A/#I3/ QA/ M3%UPAA/ BAIA/ 3+ P3*AMU9 A/#IB-)I #3%3BU#
)APA# M3/3/I#IAI 3+ 3BAAI 3@3#-% A/#I>B-)Q)3P3/)3/# C3++ CQ#-#-RI#Q 1AA)C29 A#AU M3/A#I@A/-MP+3M3/ )A/ M3/IMBU+A/ +II
REA;SI IPE II
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REA;SI IPE III)I3BU# %3AI -MP+3 IMU/ #3%*A)I AIBA#P3/IMBU/A/ -MP+3 A/#I3/>A/#IB-)I )A+AM *A%I/A/ A#AU P3MBU+UH )A%AH9 A/#IB-)I )II/IBIAA/QA *3/I Ig9 -MP+3 #3%3BU# M3/A#I@A/-MP+3M3/ QA/ 3MU)IA/ M3+3PA $AROP'AGE'E$OAI *AOR+
REA;SI IPE I:
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A)A ; *3/I #IP3 I&
3BAAI B3%IU# E49 %3AI *-/3 M-#3
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REA;SI @ONES MOE
)I#A/)AI -+3H A)A/QA I/@I+#%AI +3U-I#BA-@I+ )IBAAH 3PI)3%MI QA/ 3%I/
)I3BU# HIP3%3/I#I&I#A BA-@I+ U+I# BI+A)IC3#UA/ PA)A BI/A#A/ P3%C-BAA/9 HA+ #3%3BU# BIAA/QA )I#IMBU+A/ A/#I3/ QA/ +A%U#
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)3%MA#I#I -/#A
)3%MA#I#I QA/ #IMBU+ PA)A U+I# #3MPA# -/#A )3/A/ A+3%3/
%3AI MAIMA+ ;J *AM )A/ M3%UPAA/%3AI 3PI)3%MA+
3+ +A/3%HA/ B A/#I3/P%33/#I/ C3++ 1APC2 M3M3A/P3%A/A/
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IPE UBER;ULIN
A)A+AH %3AI )3%MA+ QA/ B3%B3)A)3/A/ %3AI )3%MA#I#I -/#A )A/
#3%*A)I 3%A#-+A3/ U+I#
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REA;SI 'RANULOMAA
M3%UAPA %3AI #IP3 I& QA/ )IA/AP
PA+I/ P3/#I/ -+3H A%3/A M3/IMBU+A/BA/QA 3@3 PA#-+-I9 A+ #3%3BU# #3%*A)I-+3H A%3/A A)A/QA A/#I3/ QA/ P3%I#3/)I )A+AM MA%-@A QA/ BIAA/QA B3%UPA
MI%--%A/IM3 QA/ #I)A )APA#)IHA/CU%A/ A#AU -MP+3 IMU/ QA/M3/3#AP MIA+/QA PA)A A+&3-+I#I A+3%I
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IPE @ONES ;ONA; UBER;ULIN 'RANULOMA
A#U
%3AI