imunitas humoral 2

8/16/2019 imunitas humoral 2

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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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. /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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. 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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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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. 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!

46


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B

dan sel dendritik untuk meningkatkan !agositosis9

4


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Opsonisasi #ba.teri .e/a"osit%

4


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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

48


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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

-

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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#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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. Ig contains γ H chain and is a monomer

Ig has ; subtypes Ig4 Ig


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eosinophils


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. 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

imunitas humoral 2

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