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I M U N O L O G II M U N O L O G I

  - Sel B dan sel T- Sel B dan sel T  - Alternative dan Lectin- Alternative dan Lectin

pathway dari komplemen  pathway dari komplemen

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Mekanisme pertahanan tubuhMekanisme pertahanan tubuh

Imunitas bawaanImunitas bawaan

imunitas alamiah,imunitas alamiah,

imunitas non spesifik,imunitas non spesifik,

innate immunity innate immunity  

natural immunity natural immunity ..

Imunitas didapatImunitas didapat

imunitas adaptif,imunitas adaptif,

imunitas spesifik,imunitas spesifik,

acquired immunity acquired immunity  

adaptive immunity adaptive immunity  

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IMUNITAS BAWAANIMUNITAS BAWAAN

IMUNITAS BAWAAN

BARIER ANATOMI BARIER HUMORAL BARIER SELULER

FAKTOR MEKANIS

FAKTOR KEMIS

FAKTOR BIOLOGIS

KOMPLEMEN

KOAGULASI

LAKTOFERIN &

 TRANSFERIN

INTERFERON

LISOZIM

INTERLEUKIN

NETROFIL

MAKROFAG

SEL NK & LAK 

EOSINOFIL

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IMUNITAS DIDAATIMUNITAS DIDAAT

IMUNITAS DIDAPAT

IMUNITAS SELULER

(LIMFOSIT T)

IMUNITAS HUMORAL

(LIMFOSIT B)

SEL T KILLER

SEL T HELPER

SEL T SUPRESSOR

SEL PLASMA

SEL B MEMORY

SEL T MEMORY

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IMUNITAS SELULER (oleh Limfosit T)Saat ma!ofa" (im#$itas %a&aa$) me$ela$ a$ti"e$ 'a$ mem%#$#h$a 

me!a$"sa$" limfosit T me$"e$al a$ti"e$Sem#a sel te!t#t#* oleh %e!%a"ai s#%sta$si ait# +l#ste! of 'iffe!e$tiatio$ (+D)

a$" ,e$is$a -./0 1l#ste! A'a .00000 mole#l *a'a *e!m#aa$ Sel T'a$ sel B

Sel B te!t#t#* oleh +D2.3 +D453 +D603 +D653 'a$ mole#l $o$ +D

Sel T te!t#t#* oleh +D23 +D43 +D63 +D273 +D65R 'a$ mole#l $o$ +D

Mole#l *a'a *e!m#aa$ limfosit me$e%a%a$ *em%e$t#a$ !ese*to!a$" %e!8a!iasi (a'a .0.7 ma1am !ese*to!)

Sel T a&al$a 'a!i tim#s melal#i 2 *!oses selesi

Selesi *ositif9 ha$a sel T a$" 1o1o 'e$"a$ !ese*to! a$" 'a*atme$"e$al mole#l MH+ a$" %e!ta$""#$",a&a% te!ha'a* *e$"e$ala$:self;

Selesi $e"atif9 'im#lai etia sel T a$" 'a*at me$"e$al mole#l MH+

%e!"a%#$" 'e$"a$ *e*ti'e asi$" 'iel#a!a$ 'a!i tim#s

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IMUNITAS SELULER (oleh Limfosit T)

A'a %e%e!a*a ma1am sel T9

Sitotosi ata# Sel T Killer (+D7

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Sistem Imun TubuhSistem Imun Tubuh

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Respon ImunRespon Imun

  Ada 4 jenis sel-sel imun yang berbeda dapatAda 4 jenis sel-sel imun yang berbeda dapatmembunuh target in vitro maupun in vivo.membunuh target in vitro maupun in vivo.

1. Sel pembunuh alami (Natural iller (N!1. Sel pembunuh alami (Natural iller (N!"ell!#"ell!#

$. "ytolyti% thymus dependent &ympho%ytes$. "ytolyti% thymus dependent &ympho%ytes("T&s!#("T&s!#

'. &ymphoine-a%tivated iller %ells (&A %ells!#'. &ymphoine-a%tivated iller %ells (&A %ells!#

4. )a%rophages4. )a%rophages

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Sel B dan sel T :Sel B dan sel T :SelSel B B 

– Plasma CellsPlasma Cells

SelSel T T – CD8CD8 T !ellsT !ells – CD"CD" T !ellsT !ells

#amma$Delta #amma$Delta SelSel  T T

%&mpho!&t merupakan salah satu dari lima komponen dari%&mpho!&t merupakan salah satu dari lima komponen darisel darah putih 'sel darah putih 'leukocytesleukocytes(, &an) beredar dalam darah.(, &an) beredar dalam darah.

Meskipun leukosit &an) matan) tampak hampir serupa akanMeskipun leukosit &an) matan) tampak hampir serupa akantetapi fun)sin&a san)atlah berbeda dan berma!am*ma!am.tetapi fun)sin&a san)atlah berbeda dan berma!am*ma!am.

%imfosit &an) terban&ak adalah +%imfosit &an) terban&ak adalah +– Limfosit B (B cells) danLimfosit B (B cells) dan

– Limfosit T (T cells).Limfosit T (T cells).Sel B diproduksi di sumsum tulan) 'Sel B diproduksi di sumsum tulan) 'bone marrow)bone marrow)..

Prekursor sel T u)a diproduksi di sumsum tulan) akanPrekursor sel T u)a diproduksi di sumsum tulan) akantetapi men)alami pematan)an di kel. Ttetapi men)alami pematan)an di kel. Thymus.hymus. 

http://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.htmlhttp://imunologi%20ekstra/B_and_Tcells.html

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Setiap sel B dan sel T !ell adalahSetiap sel B dan sel T !ell adalah spesifikspesifik terhadapterhadap antigenantigen..Tertentu, dimana ke spedifikan itu terdapat pada ba)ianTertentu, dimana ke spedifikan itu terdapat pada ba)ianreseptor dari sel tsb. -eseptor sel B 'reseptor dari sel tsb. -eseptor sel B 'BC BC ( dan reseptor sel T( dan reseptor sel T''TC TC (,.(,.

Masin)*masin) BC- dan TC- mempun&ai sifat &an) sama sbb+Masin)*masin) BC- dan TC- mempun&ai sifat &an) sama sbb+– Mereka di kodekan oleh )en &an) disusun oleh berba)aiMereka di kodekan oleh )en &an) disusun oleh berba)ai

kombinasi se)men*se)men D/.kombinasi se)men*se)men D/.– Mereka merupakan inte)ral membrane proteins.Mereka merupakan inte)ral membrane proteins.– Mereka terdapat dalam beribu ma!am kopi &an) identik &an)Mereka terdapat dalam beribu ma!am kopi &an) identik &an)

diekspose di permukaan sel..diekspose di permukaan sel..

– Mereka dibuat sebelum sel itu bertemu den)an anti)en.Mereka dibuat sebelum sel itu bertemu den)an anti)en.– Mereka mempun&ai situs pen)ikatan &an) khas..Mereka mempun&ai situs pen)ikatan &an) khas.. 

Situs itu terikat pada ba)ian dari anti)en &an) disebutSitus itu terikat pada ba)ian dari anti)en &an) disebutanti)eni! determinant atauanti)eni! determinant atau epitopeepitope..

Ikatan seperti itu men&erupai ikatan antaraIkatan seperti itu men&erupai ikatan antara en!ymeen!yme dandansubstrat"nyasubstrat"nya &) ter)antun) pada komplemen pada permukaan&) ter)antun) pada komplemen pada permukaan

reseptor dan permukaan dari epitope.reseptor dan permukaan dari epitope.Iktann&a merupakan ikatan non*!o0alent for!es , apala)i bilaIktann&a merupakan ikatan non*!o0alent for!es , apala)i biladilen)kapi den)an sin&al*sin&al tambahan, &) akandilen)kapi den)an sin&al*sin&al tambahan, &) akanmen)hasilkan +men)hasilkan +Stimulasi sel untuk menin))alkan fase #1 dan memasukki siklus sel.Stimulasi sel untuk menin))alkan fase #1 dan memasukki siklus sel.

BC- dan TC- berbeda pada struktur, )en &) men)koden&a danBC- dan TC- berbeda pada struktur, )en &) men)koden&a dan

tipe epitop &an) diikatn&atipe epitop &an) diikatn&a

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PrimaryPrimary SecondarySecondary

(Responsible for(Responsible for

aturation of Ag-reactiveaturation of Ag-reactive

cells)cells)  (Sites for Ag contact and response)(Sites for Ag contact and response)

Thymus (TThymus (T

cellcell

maturationmaturation

))

BoneBone

marrowmarrowLymph nodesLymph nodes SpleenSpleen

(T-cell(T-cell

maturation)maturation)

(B-cell(B-cellmaturationmaturation

))

  (Expansion of lymphatic(Expansion of lymphatic

system separate from bloodsystem separate from blood  circulation!circulation!

"eep cortex harbors mostly T"eep cortex harbors mostly T

  -cells superficial cortex-cells superficial cortex

  harbors mostly B -cells)harbors mostly B -cells)

(Similar to lymph(Similar to lymph

nodes but part ofnodes but part of blood circulation! blood circulation!

#ollects blood-borne#ollects blood-borne

Ags)Ags)

Jaringan Lymphoid

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LEKOSITLEKOSIT

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CELLS OF THE IMMUNE RESPONSE

#ell group#ell group Surface componentsSurface components $unction$unction

B-lymphocytesB-lymphocytes

Surface immunoglobulin (Ag recognition)Surface immunoglobulin (Ag recognition)

%mmunoglobulin $c receptor%mmunoglobulin $c receptor

#lass %% &a'or istocompatability #omplex#lass %% &a'or istocompatability #omplex

(&#) molecule (Ag presentation)(&#) molecule (Ag presentation)

"irect antigen recognition"irect antigen recognition

"ifferentiation into antibody-producing plasma cells"ifferentiation into antibody-producing plasma cells

Antigen presentation ithin #lass %% &#Antigen presentation ithin #lass %% &#

T-lymphocytesT-lymphocytes #"* molecule#"* molecule

T-cell receptor (T#R Ag recognition)T-cell receptor (T#R Ag recognition)%nvolved in both humoral and cell-mediated responses%nvolved in both humoral and cell-mediated responses

elper T-cells (Telper T-cells (T)) #"+ molecule#"+ molecule Recogni,es antigen presented ithin #lass %% &#Recogni,es antigen presented ithin #lass %% &#romotes differentiation of B-cells and cytotoxic T-cellsromotes differentiation of B-cells and cytotoxic T-cells

Activates macrophagesActivates macrophages

Suppressor T-cellsSuppressor T-cells

(T(TSS)) #". molecule

#". molecule "onregulates the activities of other cells"onregulates the activities of other cells

#ytotoxic T-cells#ytotoxic T-cells

(#T/)(#T/)

#". molecule#". moleculeRecogni,es antigen presented ithin #lass % &#Recogni,es antigen presented ithin #lass % &#

0ills cells expressing appropriate antigen0ills cells expressing appropriate antigen

Accessory cellsAccessory cells 1ariable1ariable hagocytosis and cell 2illinghagocytosis and cell 2illing

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&acrophages&acrophages%mmunoglobulin $c receptor%mmunoglobulin $c receptor

#omplement component #*b receptor#omplement component #*b receptor

#lass %% &# molecule#lass %% &# molecule

Bind $c portion of immunoglobulin (enhancesBind $c portion of immunoglobulin (enhances

 phagocytosis) phagocytosis)

Bind complement component #*b (enhancesBind complement component #*b (enhances

 phagocytosis) phagocytosis)

Antigen presentation ithin #lass %% &#Antigen presentation ithin #lass %% &#

Secrete %/-3 (macro2ine) promoting T-cell differentiationSecrete %/-3 (macro2ine) promoting T-cell differentiation

and proliferationand proliferation

#an be 4activated4 by T-cell lympho2ines#an be 4activated4 by T-cell lympho2ines

"endritic cells"endritic cells #lass %% &# molecule#lass %% &# molecule Antigen presentation ithin #lass %% &#Antigen presentation ithin #lass %% &#

olymorphonuclearolymorphonuclear

cells (&5s)cells (&5s)%mmunoglobulin $c receptor%mmunoglobulin $c receptor

#omplement component #*b receptor #omplement component #*b receptor 

Bind $c portion of immunoglobulin (enhancesBind $c portion of immunoglobulin (enhances

 phagocytosis) phagocytosis)

Bind complement component #*b (enhancesBind complement component #*b (enhances

 phagocytosis) phagocytosis)

0iller cells0iller cells1ariable1ariable "irect cell 2illing"irect cell 2illing

 50 cells 50 cells 6n2non6n2non0ills variety of target cells (e!g! tumor cells virus-0ills variety of target cells (e!g! tumor cells virus-

infected cells transplanted cells)infected cells transplanted cells)

0 cells0 cells %mmunoglobulin $c receptor %mmunoglobulin $c receptor Bind $c portion of immunoglobulinBind $c portion of immunoglobulin

0ills antibody-coated target cells (antibody-dependent0ills antibody-coated target cells (antibody-dependent

cell-mediated cytotoxicity A"##)cell-mediated cytotoxicity A"##)

&ast cells&ast cells igh affinity %gE $c receptorsigh affinity %gE $c receptors Bind %gE and initiate allergic responses by release ofBind %gE and initiate allergic responses by release ofhistaminehistamine

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KOMPONEN KOMPONEN SISTEM IMNKOMPONEN KOMPONEN SISTEM IMN

Innate immune systemInnate immune system !dapti"e immune system!dapti"e immune system

Response is non-specificResponse is non-specific athogen andathogen and antigenantigen specific responsespecific response

Exposure leads to immediate maximalExposure leads to immediate maximalresponseresponse

/ag time beteen exposure and maximal/ag time beteen exposure and maximalresponseresponse

#ell-mediated#ell-mediated and and humoralhumoral componentscomponents #ell-mediated#ell-mediated andand humoralhumoral componentscomponents

 5o 5o immunological memoryimmunological memory Exposure leads to immunological memoryExposure leads to immunological memory

$ound in nearly all forms of life$ound in nearly all forms of life $ound only in $ound only in  'aed vertebrates 'aed vertebrates

http://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Immunological_memoryhttp://en.wikipedia.org/wiki/Immunological_memoryhttp://en.wikipedia.org/wiki/Gnathostomatahttp://en.wikipedia.org/wiki/Gnathostomatahttp://en.wikipedia.org/wiki/Gnathostomatahttp://en.wikipedia.org/wiki/Gnathostomatahttp://en.wikipedia.org/wiki/Gnathostomatahttp://en.wikipedia.org/wiki/Immunological_memoryhttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Humoral_immune_responsehttp://en.wikipedia.org/wiki/Cell-mediated_immunityhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Immune_system

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Asosiasi anara s!" T d!ngan MHC #!"as I aa$ MHC

#!"as II d!ngan anig!n !yan" #erwarna merah$

http://en.wikipedia.org/wiki/File:TCR-MHC_bindings.png

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Formaion o% Anig!n &

MHC Mo"!'$"!s Comp"!(!s

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Minor lymphocyte pop%lations with limited receptor diversity Are not clonally

e&panded 'ollowin" anti"en reco"nition Interact with non classical M() like‐

molec%les

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Cor!'!pors on ) C!""s

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B Cells :B Cells :BC-s bind soluble anti)ens 'like diphtheria to2oid,BC-s bind soluble anti)ens 'like diphtheria to2oid,the protein introdu!ed into &our bod& in thethe protein introdu!ed into &our bod& in theDTP 0a!!ineDTP 0a!!ine(.(.

The bound anti)en mole!ules are en)ulfed into the BThe bound anti)en mole!ules are en)ulfed into the B!ell b&!ell b& re!eptor*mediated re!eptor*mediated endo!&tosisendo!&tosis..

The anti)en is di)ested into fra)mentsThe anti)en is di)ested into fra)ments

whi!h are then displa&ed at the !ell surfa!e nestledwhi!h are then displa&ed at the !ell surfa!e nestledinside ainside a !lass II !lass II histo!ompatibilit&histo!ompatibilit&  mole!ulemole!ule..

3elper T !ells3elper T !ells spe!ifi! for this stru!ture 'i.e., withspe!ifi! for this stru!ture 'i.e., with!omplementar& TC-s( bind the B !ell and!omplementar& TC-s( bind the B !ell and

se!retese!rete lymphokineslymphokines that+that+– stimulate the B !ell to enter the !ell !&!le and de0elop, b&stimulate the B !ell to enter the !ell !&!le and de0elop, b&

repeated mitosis, into arepeated mitosis, into a cloneclone of !ells with identi!al BC-s4of !ells with identi!al BC-s4

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/V/Vaccines.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/V/Vaccines.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th1_Th2.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th1_Th2.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/L.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/L.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/L/L.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th1_Th2.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Th_B.gifhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/V/Vaccines.html

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T Cells:T Cells:

The surfa!e of ea!h T !ell also displa&s thousands ofThe surfa!e of ea!h T !ell also displa&s thousands ofidenti!alidenti!al T cell receptorsT cell receptors ''TC TC s(.s(.There are two t&pes of T !ells that differ in their TC-+There are two t&pes of T !ells that differ in their TC-+

alpha#betaalpha#beta '56( T !ells. Their TC- is a heterodimer of an'56( T !ells. Their TC- is a heterodimer of analpha !hain with a beta !hain. 7a!h !hain has a 0ariable '(alpha !hain with a beta !hain. 7a!h !hain has a 0ariable '(re)ion and a !onstant 'C( re)ion. The re)ions ea!hre)ion and a !onstant 'C( re)ion. The re)ions ea!h!ontain 9!ontain 9 hyper$ariable regionshyper$ariable regions that make up thethat make up theanti)en*bindin) site. :anti)en*bindin) site. :%ink%ink;;gamma#deltagamma#delta '

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The !omple2 has been !ompared to a >hot do) in a bun>.The !omple2 has been !ompared to a >hot do) in a bun>.

Most of the T !ells in the bod& belon) to one of twoMost of the T !ells in the bod& belon) to one of twosubsets. These are distin)uished b& the presen!e on theirsubsets. These are distin)uished b& the presen!e on theirsurfa!e ofsurfa!e of one or the otherone or the other of twoof two )l&!oproteins)l&!oproteins desi)nated+desi)nated+

  C'C' C'C' 

?hi!h of these mole!ules is present determines what t&pes?hi!h of these mole!ules is present determines what t&pes

of !ells the T !ell !an bind to.of !ells the T !ell !an bind to.C'*C'* T !ells bind epitopes that are part ofT !ells bind epitopes that are part of class + class + histocompatibilityhistocompatibility moleculesmolecules. /lmost all the !ells of the. /lmost all the !ells of thebod& e2press !lass I mole!ules.bod& e2press !lass I mole!ules.

C'*C'* T !ells bind epitopes that are part ofT !ells bind epitopes that are part of class ++ class ++ histocompatibilityhistocompatibility moleculesmolecules. @nl& spe!ialiAed anti)en*. @nl& spe!ialiAed anti)en*

presentin) !ells e2press !lass II mole!ules.presentin) !ells e2press !lass II mole!ules.These in!lude+These in!lude+– dendriti!dendriti! !ells!ells

–  likelike macrophagesmacrophages andand

– B cellsB cells

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MHC dan C*+, T C!""s

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C'* T cellsC'* T cells

The best understood CD8 T !ells areThe best understood CD8 T !ells are cytoto,ic Tcytoto,ic Tlymphocyteslymphocytes ''CTLCTLs(.s(.

The& se!rete mole!ules that destro& the !ell to whi!h the&The& se!rete mole!ules that destro& the !ell to whi!h the&

ha0e boundha0e boundThis is a 0er& useful fun!tion if the tar)et !ell is infe!tedThis is a 0er& useful fun!tion if the tar)et !ell is infe!tedwith a 0irus be!ause the !ell is usuall& destro&ed before itwith a 0irus be!ause the !ell is usuall& destro&ed before it!an release a fresh !rop of 0iruses able to infe!t other !ells.!an release a fresh !rop of 0iruses able to infe!t other !ells.

In )eneral, the role of the CD8 T !ells is to monitor all theIn )eneral, the role of the CD8 T !ells is to monitor all the!ells of the bod&, read& to destro& an& that e2press forei)n!ells of the bod&, read& to destro& an& that e2press forei)n

anti)en fra)ments in their !lass I mole!ules. In )eneral, theanti)en fra)ments in their !lass I mole!ules. In )eneral, therole of the CD8 T !ells is to monitor all the !ells of therole of the CD8 T !ells is to monitor all the !ells of thebod&, read& to destro& an& that e2press forei)n anti)enbod&, read& to destro& an& that e2press forei)n anti)enfra)ments in their !lass I mole!ules.fra)ments in their !lass I mole!ules.

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A'i-aion o% Cyoo(i' T C!""s

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CTL.

 - dapa m!m/$n$h s!" asing s!!"ah dipr!s!nasi#an o"!h MHC #!"as I0

 1 s!/agai s!"1s!" !%!#or $ama da"am p!no"a#an s!"2s!" asing

 1 CTLs dapa m!m/$n$h s!"1s!" arg! m!"a"$i 3 pah4ay 5

  60 Pah4ay p!rama. yang m!"i/a#an s!#r!si pro!in dan pro!as!

  s!rin a"ami yang #!d$anya ada da"am gran$"a $ni# pada CTLs

 

30 Pah4ay #!d$a. m!m!r"$#an 'ross1"in#!d "igands p!rm$#aan

pada CTLs d!ngan r!s!por p!rm$#aan sp!si%i# pada s!"1s!"

  sasaran $n$# m!rangsang apoposis s!"1s!" i$ 7program

#!maian s!"80

 

C9TOL9TIC TH9MUS1*EPEN*ENT L9MPHOC9TES

7CTLs8 2 Cyoo(i' T '!""s

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C'* T cellsC'* T cells

CD" T !ells bind an epitope !onsistin) of an anti)en fra)mentCD" T !ells bind an epitope !onsistin) of an anti)en fra)mentl&in) in the )roo0e of al&in) in the )roo0e of a !lass II !lass II histo!ompatibilit&histo!ompatibilit&  mole!ulemole!ule..CD" T !ells are essential for both theCD" T !ells are essential for both the !ell*mediated!ell*mediated andand

antibod&*mediated bran!hes of the immune s&stem+antibod&*mediated bran!hes of the immune s&stem+cell"mediated immunitycell"mediated immunity These CD" !ells bind to anti)en presented b& anti)en*These CD" !ells bind to anti)en presented b& anti)en*presentin) !ells '/PCs( like pha)o!&ti!presentin) !ells '/PCs( like pha)o!&ti! ma!ropha)esma!ropha)es andanddendriti!dendriti! !ells!ells. The T !ells then release. The T !ells then release lymphokineslymphokines thatthatattra!t other !ells to the area. The result isattra!t other !ells to the area. The result is inflammationinflammation+ the+ the

a!!umulation of !ells and mole!ules that attempt to wall offa!!umulation of !ells and mole!ules that attempt to wall offand destro& the anti)eni! material 'an abs!ess is one e2ample,and destro& the anti)eni! material 'an abs!ess is one e2ample,the rash followin) e2posure to poison i0& is another(.the rash followin) e2posure to poison i0& is another(.

antibody"mediated immunityantibody"mediated immunity These CD" !ells, !alledThese CD" !ells, !alled helper T cellshelper T cells, bind to anti)en, bind to anti)enpresented b& B !ells 'presented b& B !ells 'as shown abo0eas shown abo0e(. The result is the(. The result is thede0elopment ofde0elopment of clonesclones ofof plasma cellsplasma cells se!retin) antibodiesse!retin) antibodies

a)ainst the anti)eni! material.a)ainst the anti)eni! material.

/IDS pro0ides a 0i0id and tra)i! illustration of the importan!e of CD" T !ells in/IDS pro0ides a 0i0id and tra)i! illustration of the importan!e of CD" T !ells inimmunit&. The human immunodefi!ien!& 0irus 'immunit&. The human immunodefi!ien!& 0irus '-+-+( binds to CD" mole!ules and thus is( binds to CD" mole!ules and thus isable to in0ade and infe!t CD" T !ells. /s the disease pro)resses, the number of CD" Table to in0ade and infe!t CD" T !ells. /s the disease pro)resses, the number of CD" T!ells de!lines below its normal le0el of about 111 per mi!roliter 'l(. '/ partial!ells de!lines below its normal le0el of about 111 per mi!roliter 'l(. '/ partiale2planation for this ma& be the un!easin) efforts of the patientEs CD8 T !ells to destro&e2planation for this ma& be the un!easin) efforts of the patientEs CD8 T !ells to destro&the infe!ted CD" !ells.the infe!ted CD" !ells.

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H!"p!r T1 C!""s

http://en.wikipedia.org/wiki/File:Lymphocyte_activation_simple.png

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A#i-asi S!" T sp!si%i# 1 anig!n

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Fnlike adapti0e T !ells, ha0e a TC-Fnlike adapti0e T !ells, ha0e a TC-!omposed of a heterodimer of

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&ymphoine-A%tivated&ymphoine-A%tivated

iller %ells (&A %ells!iller %ells (&A %ells!

&A %ells#&A %ells#

Subset null lympho%yte berbeda dariSubset null lympho%yte berbeda dari

sel-sel N dan "T&s.sel-sel N dan "T&s.*apat dihasilan in vitro# %aranya*apat dihasilan in vitro# %aranya

mengul-mengul-

tur sel-sel lim+osit , interleuin-$# onsen-tur sel-sel lim+osit , interleuin-$# onsen-

trasi I&-$ tinggitrasi I&-$ tinggi)emilii ativitas anti tumor (membunuh)emilii ativitas anti tumor (membunuh

sel tumor!.sel tumor!.

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Ki""!r T '!""s

SEL NK ($at#!al ille!) = LAK (lm*hoi$e a1ti8ate' ille!)SEL NK ($at#!al ille!) = LAK (lm*hoi$e a1ti8ate' ille!)

http://en.wikipedia.org/wiki/File:Cytotoxic_T_cell.jpg

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SEL NK ($at#!al ille!) = LAK (lm*hoi$e a1ti8ate' ille!)SEL NK ($at#!al ille!) = LAK (lm*hoi$e a1ti8ate' ille!)Se1a!a $o$ s*esifiSe1a!a $o$ s*esifi mem%#$#h 8i!#s 'a$ sel>sel t#mo!mem%#$#h 8i!#s 'a$ sel>sel t#mo!

B#a$B#a$ %a"ia$ 'a!i%a"ia$ 'a!i !es*o$ !a'a$"!es*o$ !a'a$" 

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S!"1s!" NK dapa m!m/$n$h s!"1s!" sasaran anpa

m!nsin!sa s!/!"$mnya Anig!n sp!si%i#. a#i-ias1

nya ida# m!m!r"$#an adanya MHC #!"as I pada

s!"1s!" arg!0

*ip!r#ira#an s!"1s!" NK am/i" /agian da"am p!nga1

4asan $mor yang m$"ai im/$" dan

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Sel N#Sel N#

mungin salah satu dari sel T Sitotosi mungin salah satu dari sel T Sitotosi 

)empunyai reseptor yang beriatan dengan bagian)empunyai reseptor yang beriatan dengan bagiandari moleul Ig.dari moleul Ig.

Saat beriatan# sel-sel N memasuan suatu proteinSaat beriatan# sel-sel N memasuan suatu proteine sele sel

  target# menyebaban sel target membenga dantarget# menyebaban sel target membenga danpe%ah.pe%ah.

  )arernya "* 1)arernya "* 1

 

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NATURAL KILLER CELLS

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NK '!""s* N+ cells mer%pakan s%at% "r%p y"

  dise#%t ,lar"e "ran%lar lymphocytes,* Sel-sel ini #ersi'at non-speci'ic. M()-

  %nrestricted cells #erperan %nt%k

eliminasi sel-sel neoplastik ata% t%mor.* Mekanisme #a"aimana sel ini

men"enal  sel sasarannya #el%m diketah%i secara

 /elas* +em%n"kinan terdapat #e#erapa tipe

  N+-determinant y" diekspresikan oleh

  sel sasaran y" dikenal oleh reseptor   N+-receptor pd perm%kaan sel N+ * Be"it% sel sasaran dikenali

pem%snahan m%n"kin sama den"an

  cara ker/a )TL

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)a%rophages)a%rophages

Sel +agosit mono nuleus non lim+ositSel +agosit mono nuleus non lim+osit

Ada pada jaringan dan dalam darah# derivatAda pada jaringan dan dalam darah# derivatdaridari

stem sel monositi%.stem sel monositi%.

/enting sebagai sel pelengap pada respon/enting sebagai sel pelengap pada responimunimun

)aro+ag husus ada pada beberapa loasi# sel-)aro+ag husus ada pada beberapa loasi# sel-selsel

up0er dan histiosit.up0er dan histiosit.

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MAKROFA?MAKROFA?

Ma!ofa" 'a$ mo$osit a$" %a!#Ma!ofa" 'a$ mo$osit a$" %a!#

'i!e!#t mela#a$'i!e!#t mela#a$ fa"ositosisfa"ositosis se!tase!tamem%#$#hmem%#$#h mi!oo!"a$ismemi!oo!"a$isme 'i'i'alam sel'alam sel

Ma!ofa" ,#"a mam*#Ma!ofa" ,#"a mam*# mem%#$#hmem%#$#hse1a!a est!asel#le!se1a!a est!asel#le!

Ma!ofa" me$'##$" *e!%aia$Ma!ofa" me$'##$" *e!%aia$ ,a!i$"a$ 'a$ %e!asi se%a"ai ,a!i$"a$ 'a$ %e!asi se%a"aia$ti"e$>*!ese$ti$" 1ells (AP+)a$ti"e$>*!ese$ti$" 1ells (AP+)33a$" 'i*e!l#a$ #$t# memi1#a$" 'i*e!l#a$ #$t# memi1#!es*o$ im#$ s*esifi!es*o$ im#$ s*esifi

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Fungsi Complement Fungsi Complement 

ComplementComplement merupakan suatu )rup protein serum &an) berkera seba)aimerupakan suatu )rup protein serum &an) berkera seba)ai

komplemen akti0itas antibodi untuk melen&apkan pato)en.komplemen akti0itas antibodi untuk melen&apkan pato)en.

/dalah suatu kaskade enAim &an) membentu pertahanan tubuh thd/dalah suatu kaskade enAim &an) membentu pertahanan tubuh thdinfeksi.infeksi.

Complement bukan bersifat spesifik thd anti)en dan komponenn&aComplement bukan bersifat spesifik thd anti)en dan komponenn&a

diaktifkan den)an se)era bila terdapat pato)en, sehin))a di)olon)kandiaktifkan den)an se)era bila terdapat pato)en, sehin))a di)olon)kandalam imunitas didapat 'innate immunit&(. /kan tetapi adapula anti)endalam imunitas didapat 'innate immunit&(. /kan tetapi adapula anti)en&an) dapt men)aktifkan protein komplemen sehin))a akti0asi komplemen&an) dapt men)aktifkan protein komplemen sehin))a akti0asi komplemenseba)ian di)olon)kan pula dalamseba)ian di)olon)kan pula dalam humoral immunityhumoral immunity..

Complement menstimulasi inflamasi, memfasilitasi fa)ositosis anti)en danComplement menstimulasi inflamasi, memfasilitasi fa)ositosis anti)en danlisis dari beberapa ma!am sel se!ara lan)sun).Garena merupakan suatulisis dari beberapa ma!am sel se!ara lan)sun).Garena merupakan suatua)en inflamasi &an) kuat maka akti0itasn&a dire)ulasi se!ara ketat..a)en inflamasi &an) kuat maka akti0itasn&a dire)ulasi se!ara ketat..

Complement protein diproduksi se!ara konstitutif oleh makrofa) danComplement protein diproduksi se!ara konstitutif oleh makrofa) danhepatosit. H) terdapat dalam sirkulasi merupakan seba)ai molekul &)hepatosit. H) terdapat dalam sirkulasi merupakan seba)ai molekul &)belum aktif. Seba)ian besar protein komplemen merupakanbelum aktif. Seba)ian besar protein komplemen merupakan pro"en!ymepro"en!yme(!ymogen)(!ymogen) dan seba)ian ditemukan pula pada permukaan sel..dan seba)ian ditemukan pula pada permukaan sel..

Complement proteins o!!ur in serum as ina!ti0e enA&me pre!ursorsComplement proteins o!!ur in serum as ina!ti0e enA&me pre!ursors

'A&mo)ens(4 others reside on !ell surfa!es.'A&mo)ens(4 others reside on !ell surfa!es.

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Sistem complementSistem complement ++

Sistem komplemen menembatani antara innateSistem komplemen menembatani antara innatedan a!uired immunit& melalui +dan a!uired immunit& melalui +– Memperbesar respons antibod& '/b( responses danMemperbesar respons antibod& '/b( responses dan

immunolo)i! memor&immunolo)i! memor&

– Melisiskan selsel asin)Melisiskan selsel asin)

–Membersihkan kompleks imun dan sel &) men)alamiMembersihkan kompleks imun dan sel &) men)alamiapoptosis.apoptosis.

– Gomponen* komponen komplemen mempun&ai ban&akGomponen* komponen komplemen mempun&ai ban&akfun)si biolo)is 'a,l. Stimulasi proses !hemota2is, memi!ufun)si biolo)is 'a,l. Stimulasi proses !hemota2is, memi!ude)ranulasi sel mast tanpa ter)antun) pada I)7(.de)ranulasi sel mast tanpa ter)antun) pada I)7(.

/kti0asi komplemen+ Terdapat 9 alur pen)aktifan/kti0asi komplemen+ Terdapat 9 alur pen)aktifan

komplemen+komplemen+– Classi!alClassi!al

– %e!tin%e!tin

– /lternati0e/lternati0e

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Classical pathwayClassical pathway 

/kti0asi dependen thd /b, teradi bila C berinteraksi/kti0asi dependen thd /b, teradi bila C berinteraksi

den)an /)*I)M atau a))re)ated /)*I)# !omple2es,den)an /)*I)M atau a))re)ated /)*I)# !omple2es,atau /b*independent, &) teradi bila pol&anion 'e),atau /b*independent, &) teradi bila pol&anion 'e),heparin, protamine, D/ dan -/ dari sel apoptoti!(,heparin, protamine, D/ dan -/ dari sel apoptoti!(,)ram*ne)ati0e ba!teria, atau terikat pada C*rea!ti0e)ram*ne)ati0e ba!teria, atau terikat pada C*rea!ti0eprotein &) bereaksi lan)sun) den)an C.protein &) bereaksi lan)sun) den)an C.

Pathwa& ini dire)ulasi oleh C inhibitor 'C*I3(.Pathwa& ini dire)ulasi oleh C inhibitor 'C*I3(.Lectin pathwayLectin pathway 

/kti0asi adalah /b*independent4 &an) teradi bila/kti0asi adalah /b*independent4 &an) teradi bilamannose*bindin) le!tin 'MB%(, suatu protein serum,mannose*bindin) le!tin 'MB%(, suatu protein serum,terikat pada )u)us manosa atau fruktosa pada dindin)terikat pada )u)us manosa atau fruktosa pada dindin)

sel bakteri, dindin) sel ra)i '&east(, atau 0irus.sel bakteri, dindin) sel ra)i '&east(, atau 0irus.Se!ara fun)sionil dan struktural alur ini men&erupaiSe!ara fun)sionil dan struktural alur ini men&erupai alur klasik. alur klasik.

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L/CT+0 &%T-1%2L/CT+0 &%T-1%2 

3annose"binding lectin3annose"binding lectin ''3BL3BL(( cascadecascade memerlukan sintesismemerlukan sintesisMB% oleh hati seba)ai awaban terhadap sitokin inflamasi dariMB% oleh hati seba)ai awaban terhadap sitokin inflamasi dari

Jalur ini diinisiasi oleh ikatan MB% pada permukaan bakteri &)Jalur ini diinisiasi oleh ikatan MB% pada permukaan bakteri &)

mempun&ai polisakarida &an) men)andun) manosa 'mannans(.mempun&ai polisakarida &an) men)andun) manosa 'mannans(.Ikatan antara MB% pada pato)en men)hasilkan dua ma!amIkatan antara MB% pada pato)en men)hasilkan dua ma!amprotease serin &aitu M/SP* dan M/SP*K 'L MB%*asso!iatedprotease serin &aitu M/SP* dan M/SP*K 'L MB%*asso!iatedserine proteases(. M/SP* and M/SP*K adalah sama den)an Crserine proteases(. M/SP* and M/SP*K adalah sama den)an Crdan Cs, dan MB% adalah sama den)an C. Pembentukandan Cs, dan MB% adalah sama den)an C. PembentukanMB%$M/SP*$M/SP*K tri*mole!ular !omple2 menhasilkanMB%$M/SP*$M/SP*K tri*mole!ular !omple2 menhasilkanpen)aktifan dari kedua M/SP dan pembelahan selanutn&a daripen)aktifan dari kedua M/SP dan pembelahan selanutn&a dari

C" menadi C"a dan C"b. ra)men C"b terikat pada membranC" menadi C"a dan C"b. ra)men C"b terikat pada membrandan fra)men C"a dibebaskan pada lin)kun)an mikro itu dandan fra)men C"a dibebaskan pada lin)kun)an mikro itu danakti0asi kedua M/SP u)a meme!ah CK menadi CKa dan CKb.akti0asi kedua M/SP u)a meme!ah CK menadi CKa dan CKb.CKa kmdn terikat pada membran &) berasosiasi den)an C"b danCKa kmdn terikat pada membran &) berasosiasi den)an C"b danCKb kemudian dibebaskan ke lin)kun)an mikro itu.CKb kemudian dibebaskan ke lin)kun)an mikro itu.

Gompleks C"bCKa &) terbentuk merupakan suatu C9 !on0ertase,Gompleks C"bCKa &) terbentuk merupakan suatu C9 !on0ertase,

&an) berikutn&a akan membelah C9 menadi C9a dan C9b. C9b&an) berikutn&a akan membelah C9 menadi C9a dan C9b. C9bakan terikat pada membran dalam asosiasi den)an C"b dan CKaakan terikat pada membran dalam asosiasi den)an C"b dan CKadan C9a akan dibebaskan pada lin)kun)an mikro tersebut.dan C9a akan dibebaskan pada lin)kun)an mikro tersebut.

Gompleks C"bCKaC9b &) terbentu asalah suatu CN !on0ertase.Gompleks C"bCKaC9b &) terbentu asalah suatu CN !on0ertase.Pembentukan CN !on0ertase merupakan akhir dari le!tin pathwa&.Pembentukan CN !on0ertase merupakan akhir dari le!tin pathwa&.

%kti$itas biologis dan protein regulasi 4alur lectin adalah%kti$itas biologis dan protein regulasi 4alur lectin adalah

sama dengan 4alur klasik.sama dengan 4alur klasik.

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Table 1. Proteins of the Complement systemTable 1. Proteins of the Complement system

Classical PathwayClassical Pathway LectinLectin PathwayPathway Alternative PathwayAlternative Pathway Lytic PathwayLytic Pathway

A1ti8atio$ P!otei$s9A1ti8atio$ P!otei$s9

+.@+.@!s!s3 +3 +223 +43 +63 +43 +6 

+o$t!ol P!otei$s9+o$t!ol P!otei$s9

+.>INH3 +6>BP+.>INH3 +6>BP 

Ma$$a$ %i$'i$" *!otei$ (MBP)3Ma$$a$ %i$'i$" *!otei$ (MBP)3

ma$$a$>aso1iate' se!i$ema$$a$>aso1iate' se!i$e

*!otease (MASP3 MASP2)*!otease (MASP3 MASP2)

 

+43 Fa1to!s+43 Fa1to!s BB = D= D33

P!o*e!'i$ (P)P!o*e!'i$ (P) 

Fa1to!s IFa1to!s I = H3 'e1a= H3 'e1a

a11ele!ati$" fa1to! (DAF)3a11ele!ati$" fa1to! (DAF)3

+om*leme$t !e1e*to!+om*leme$t !e1e*to!

.(+R.)3.(+R.)3 etcetc

 +53 +/3 +3 +73 +C+53 +/3 +3 +73 +C 

P!otei$ SP!otei$ S

+om*o$e$ts+om*o$e$ts #$'e!li$e'#$'e!li$e' a1@#i!e e$mati1 a1ti8it &he$ a1ti8ate'a1@#i!e e$mati1 a1ti8it &he$ a1ti8ate'

+om*o$e$ts ma!e' &ith a$ aste!is ha8e e$mati1 a1ti8it i$ thei! $ati8e fo!m+om*o$e$ts ma!e' &ith a$ aste!is ha8e e$mati1 a1ti8it i$ thei! $ati8e fo!m

http://cgap.nci.nih.gov/Pathways/BioCarta/h_classicPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_classicPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_alternativePathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_alternativePathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_alternativePathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_lectinPathwayhttp://cgap.nci.nih.gov/Pathways/BioCarta/h_classicPathway

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#omponents o$ the #lassical Pathway#omponents o$ the #lassical Pathway

Nati"eNati"e

componcompon

entent

!cti"e!cti"e

componecompone

nt(s)nt(s)%unction(s)%unction(s)

#3(7rs#3(7rs

))

#37#37Binds to antibody that has boundBinds to antibody that has bound

antigen activates #3r!antigen activates #3r!

#3r #3r #leaves #3s to activate protease#leaves #3s to activate protease

function!function!

#3s#3s #leaves #8 and #+!#leaves #8 and #+!

#8#8#8a#8a 6n2non!6n2non!

#8b#8bActive en,yme of classicalActive en,yme of classical

 pathay9 cleaves #* and #:! pathay9 cleaves #* and #:!

#*#*

#*a#*a&ediates inflammation9&ediates inflammation9

anaphylatoxin!anaphylatoxin!

#*b#*b

Binds #: for cleavage by #8b!Binds #: for cleavage by #8b!

Binds cell surfaces forBinds cell surfaces for

opsoni,ation and activation ofopsoni,ation and activation ofalternate pathay!alternate pathay!

#+#+

#+a#+a &ediates inflammation!&ediates inflammation!

#+b#+bBinds #8 for cleavage by #3s!Binds #8 for cleavage by #3s!

Binds cell surfaces forBinds cell surfaces for

opsoni,ation!opsoni,ation!

)omponent cleava"e

0n1ymatic activity

)omponent assem#ly

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#omponents o$ the !lternate Pathway#omponents o$ the !lternate Pathway

Nati"eNati"ecomponcompon

entent

!cti"e!cti"ecomponecompone

nt(s)nt(s)%unction(s)%unction(s)

#*#*

#*a#*a&ediates inflammation9&ediates inflammation9

anaphylatoxin!anaphylatoxin!

#*b#*bBinds cell surfaces for opsoni,ationBinds cell surfaces for opsoni,ation

and activation of alternate pathay!and activation of alternate pathay!

$actor B$actor B

BBBinds membrane bound #*b!Binds membrane bound #*b!

#leaved by $actor "!#leaved by $actor "!

BaBa 6n2non!6n2non!

BbBb#leaved form stabili,ed by #leaved form stabili,ed by

 produces #* convertase! produces #* convertase!

$actor "$actor " ""#leaves $actor B hen bound to#leaves $actor B hen bound to

#*b!#*b!

roperdiroperdi

nn

Binds and stabili,es membraneBinds and stabili,es membrane

 bound #*bBb! bound #*bBb!)omponent cleava"e

0n1ymatic activity

)omponent assem#ly

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#omponents o$ the Mem&rane'!ttac #omple#omponents o$ the Mem&rane'!ttac #omple

Nati"e componentNati"e component !cti"e component(s)!cti"e component(s) %unction(s)%unction(s)

#:#:

#:a#:a &ediates inflammation9 anaphylatoxin chemotaxin!&ediates inflammation9 anaphylatoxin chemotaxin!

#:b#:b %nitiates assembly of the membrane-attac2 complex (&A#)!%nitiates assembly of the membrane-attac2 complex (&A#)!

#;#; #;#; Binds #:b forms acceptor for #

#

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%lternate pathway%lternate pathway 

/kti0asi teradi bila komponen permukaan sel/kti0asi teradi bila komponen permukaan sel

mikroba 'a.l., &east walls, ba!terial !ell wallmikroba 'a.l., &east walls, ba!terial !ell walllipopol&sa!!haride :endoto2in;( atau I) 'a.l.,lipopol&sa!!haride :endoto2in;( atau I) 'a.l.,nephriti! fa!tor, a))re)ated I)/( meme!ahnephriti! fa!tor, a))re)ated I)/( meme!ahseba)ian ke!il C9.seba)ian ke!il C9.

Jalur ini dire)ulasi oleh properdin, fa!tor 3, danJalur ini dire)ulasi oleh properdin, fa!tor 3, dan

de!a&*a!!eleratin) fa!tor.de!a&*a!!eleratin) fa!tor.Ge 9 alur itu kemudian akan men)eru!ut menadiGe 9 alur itu kemudian akan men)eru!ut menadisuatu alur final bersama bilamana C9 !on0ertasesuatu alur final bersama bilamana C9 !on0ertasememe!ah C9 menadi C9a dan C9bmeme!ah C9 menadi C9a dan C9b

Peme!ahan C9 akan men)hasilkan pembentukanPeme!ahan C9 akan men)hasilkan pembentukan

membrane attack comple, (3%C)5membrane attack comple, (3%C)5 &)&)merupakan komponen sitotoksik sistemmerupakan komponen sitotoksik sistemkomplemen. M/C men&ebabkan l&sis dari sel*selkomplemen. M/C men&ebabkan l&sis dari sel*selasin).asin).

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6ormation of the 3embrane %ttack Comple,6ormation of the 3embrane %ttack Comple,(3%C)(3%C):: 

/kti0asi komplemen stimulasi berba)ai akti0itas antimikrobial./kti0asi komplemen stimulasi berba)ai akti0itas antimikrobial.Titik akhir adalah pembentukanTitik akhir adalah pembentukan membrane attack comple,membrane attack comple, ''3%C3%C(, &) akan berinsersi ke pada lipid membran bakteri atau(, &) akan berinsersi ke pada lipid membran bakteri atausel eukariot dan men&ebabkan lisis osmotik.sel eukariot dan men&ebabkan lisis osmotik.

Be)itu C9 !on0ertase terbentuk baik dari alur klasik atauBe)itu C9 !on0ertase terbentuk baik dari alur klasik ataualternatif suatu seri kaskade enAimatik teradi &) berakhiralternatif suatu seri kaskade enAimatik teradi &) berakhirden)an pembentukanden)an pembentukan 3embrane %ttack Comple, (3%C).3embrane %ttack Comple, (3%C). 

Gaskade ini termasuk pen)ikatan sekuensial CEO '!omplementGaskade ini termasuk pen)ikatan sekuensial CEO '!omplementprotein O(, CE dan CE8 pd permukaan sel asin).protein O(, CE dan CE8 pd permukaan sel asin).

 Gompleks ini men)induksi polimerisasi amak molekul CEQ.Gompleks ini men)induksi polimerisasi amak molekul CEQ.

Protein*orotein ini akan men&usun diri pada membran plasma selProtein*orotein ini akan men&usun diri pada membran plasma selsasaran dan membentuk sebuah pori &) akan men&ebabkan airsasaran dan membentuk sebuah pori &) akan men&ebabkan airdan molekul*molekul )aram keluar dan akan merusak sel itudan molekul*molekul )aram keluar dan akan merusak sel itu

melalui lisis osmotik.melalui lisis osmotik.

C " i i h

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Comp"!m!n a'i-aion pah4ays0

The classical. lectin. and alternative pathways conver"e into a 'inal common pathway when )2

convertase !)2 con$ cleaves )2 into )2a and )2# A# 3 anti#ody4 A" 3 anti"en4 )5-IN( 3 )5 inhi#itor4

MA) 3 mem#rane attack comple&4 MAS 3 MBL-associated serine protease4 MBL 3 mannose-#indin"

lectin4 3 properdin 6ver#ar indicates activation 

Biologic acti$itiesBiologic acti$ities+

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Biologic acti$itiesBiologic acti$ities++Complement !omponents ha0e other immune fun!tions thatComplement !omponents ha0e other immune fun!tions thatare mediated b& !omplement re!eptors 'C-( on 0arious !ells.are mediated b& !omplement re!eptors 'C-( on 0arious !ells.

C- 'CD9N( promotes pha)o!&tosis and helps !lear immuneC- 'CD9N( promotes pha)o!&tosis and helps !lear immune!omple2es.!omple2es.

C-K 'CDK( re)ulates /b produ!tion b& B !ells and is theC-K 'CDK( re)ulates /b produ!tion b& B !ells and is the7pstein*Barr 0irus re!eptor.7pstein*Barr 0irus re!eptor.

C-9 'CDb$CD8(, C-" 'CD!$CD8(, and C re!eptorsC-9 'CDb$CD8(, C-" 'CD!$CD8(, and C re!eptorspla& a role in pha)o!&tosis.pla& a role in pha)o!&tosis.

C9a, CNa, and C"a 'weakl&( ha0e anaph&lato2in a!ti0it&+ The&C9a, CNa, and C"a 'weakl&( ha0e anaph&lato2in a!ti0it&+ The&!ause mast !ell de)ranulation, leadin) to in!reased 0as!ular!ause mast !ell de)ranulation, leadin) to in!reased 0as!ularpermeabilit& and smooth mus!le !ontra!tion.permeabilit& and smooth mus!le !ontra!tion.C9b a!ts as an opsonin b& !oatin) mi!roor)anisms andC9b a!ts as an opsonin b& !oatin) mi!roor)anisms andthereb& enhan!in) their pha)o!&tosis.thereb& enhan!in) their pha)o!&tosis.

C9d enhan!es /b produ!tion b& B !ells.C9d enhan!es /b produ!tion b& B !ells.

CNa is a neutrophil !hemoattra!tant4 it re)ulates neutrophilCNa is a neutrophil !hemoattra!tant4 it re)ulates neutrophiland mono!&te a!ti0ities and ma& !ause au)mented adheren!eand mono!&te a!ti0ities and ma& !ause au)mented adheren!e

of !ells, de)ranulation and release of intra!ellular enA&mesof !ells, de)ranulation and release of intra!ellular enA&mesfrom )ranulo!&tes, produ!tion of to2i! o2&)en metabolites,from )ranulo!&tes, produ!tion of to2i! o2&)en metabolites,and initiation of other !ellular metaboli! e0ents.and initiation of other !ellular metaboli! e0ents.

3ereditar& an)ioedema is due to a )eneti! defi!ien!& of C*3ereditar& an)ioedema is due to a )eneti! defi!ien!& of C*I3.I3.

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B+7L78+C%LL2 %CT+/ &7'9CTS dari %T+%S+ 73&L/3/0B+7L78+C%LL2 %CT+/ &7'9CTS dari %T+%S+ 73&L/3/0 

/kti0asi komplemen men)hasilkan produksi seumlah molekul biolo)is &an)/kti0asi komplemen men)hasilkan produksi seumlah molekul biolo)is &an)aktif &) berkontribusi oada teradin&a resistan!e, anaph&la2is danaktif &) berkontribusi oada teradin&a resistan!e, anaph&la2is daninflammation..inflammation..

inin productioninin productionCKb &) dihasilkan pd alur klasik dari pen)aktifan C merupakan suatuCKb &) dihasilkan pd alur klasik dari pen)aktifan C merupakan suatuprokinin &) akan menadi aktif se!ara biolo)is setelah men)alami alterasiprokinin &) akan menadi aktif se!ara biolo)is setelah men)alami alterasienAimatik oleh plasmin. Gelebihan produksi CKb di!e)ah oleh pembatasanenAimatik oleh plasmin. Gelebihan produksi CKb di!e)ah oleh pembatasanakti0asi CK a!ti0ation oleh C inhibitor 'C*I3( &) dikenal pula seba)aiakti0asi CK a!ti0ation oleh C inhibitor 'C*I3( &) dikenal pula seba)aiserpin &) men))antikan Crs dari kompleks Crs.serpin &) men))antikan Crs dari kompleks Crs.

Suatu defisiensi )ene"tik dari C*I3 men&ebabkan o0erproduksi dari CKbSuatu defisiensi )ene"tik dari C*I3 men&ebabkan o0erproduksi dari CKbdan men&ebabkan hereditar& an)ioneuroti! edema. Geadaan ini dapatdan men&ebabkan hereditar& an)ioneuroti! edema. Geadaan ini dapatdiperbaiki den)an DanaAol &) mempromosikan produksi C*I3 atau asamdiperbaiki den)an DanaAol &) mempromosikan produksi C*I3 atau asamR*amino !aproi! &) dapat menurunkan akti0itas plasmin.R*amino !aproi! &) dapat menurunkan akti0itas plasmin.

%naphyloto,ins%naphyloto,insC"a, C9a dan CNa merupakan anaph&loto2ins &) men&ebabkanC"a, C9a dan CNa merupakan anaph&loto2ins &) men&ebabkanbasophil$mast !ell de)ranulation dan smooth mus!le !ontra!tion. 7dek &)basophil$mast !ell de)ranulation dan smooth mus!le !ontra!tion. 7dek &)tidak diin)inkan dari peptida ini dapat dikontrol oleh pemberiantidak diin)inkan dari peptida ini dapat dikontrol oleh pemberian!arbo2&peptidase B 'C9a*I/(.!arbo2&peptidase B 'C9a*I/(.

Chemotactic 6actorsChemotactic 6actorsCNa dan M/C 'CNbO( bersifat !hemota!ti!. CNa u)a merupakan akti0atorCNa dan M/C 'CNbO( bersifat !hemota!ti!. CNa u)a merupakan akti0atorkuat dari neutrophils, basophils dan ma!ropha)es dan men&ebabkankuat dari neutrophils, basophils dan ma!ropha)es dan men&ebabkaninduksi molekul adhesi dan sel*sel endotel 0askuler..induksi molekul adhesi dan sel*sel endotel 0askuler..

7psonins7psoninsC9b dan C"b pada permukaan mikroor)anisme akan menempel pada C*C9b dan C"b pada permukaan mikroor)anisme akan menempel pada C*re!eptor 'C-( pada sel pha)o!&ti! dan men&ebabkan pha)o!&tosis.re!eptor 'C-( pada sel pha)o!&ti! dan men&ebabkan pha)o!&tosis.

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Biologically acti$e products dari akti$asi CBiologically acti$e products dari akti$asi C

De)radaei produk C9 'iC9b, C9d and C9e( u)a daparDe)radaei produk C9 'iC9b, C9d and C9e( u)a dapar

terikat pada berba)ai ma!am sel oleh reseptor khususterikat pada berba)ai ma!am sel oleh reseptor khususdan akan memodulasi fun)si dari sel itu.dan akan memodulasi fun)si dari sel itu.

Ju)a terdapat defisiensi )enetik pada indi0idu tertentuJu)a terdapat defisiensi )enetik pada indi0idu tertentupada komponen komplemen C, dan ditemukan pulapada komponen komplemen C, dan ditemukan puladiantaran&a defisiensi C9 )en)an akibat serius dandiantaran&a defisiensi C9 )en)an akibat serius dan

fatal. Defisiensi komplemen u)a ditemukan padafatal. Defisiensi komplemen u)a ditemukan padaimmune !omple2 diseases 'e.)., S%7( a!ute danimmune !omple2 diseases 'e.)., S%7( a!ute dan!hroni! ba!terial, 0iral dan parasiti! infe!tions.!hroni! ba!terial, 0iral dan parasiti! infe!tions.

  ingkasan : sistem komplemen berperaningkasan : sistem komplemen berperanpada resistensi spesifik maupun non"pada resistensi spesifik maupun non"

spesifik dan menghasilkan berbagaispesifik dan menghasilkan berbagaiproduk biologis dan patofisiologis yangproduk biologis dan patofisiologis yangsignifikansignifikan

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Ta&le *+ !cti"ities o$ #omplement !cti"ation Products and their #ontrol %actorsTa&le *+ !cti"ities o$ #omplement !cti"ation Products and their #ontrol %actors

$ragment$ragment ActivityActivity EffectEffect #ontrol $actor (s)#ontrol $actor (s)

#8a#8a ro2inin accumulation of fluidsro2inin accumulation of fluids EdemaEdema #3-%5#3-%5

#*a#*aBasophil and mast cells degranulation9 enhancedBasophil and mast cells degranulation9 enhanced

vascular permeability smooth musclevascular permeability smooth muscle

contractioncontractionAnaphylaxisAnaphylaxis #*a-%5A#*a-%5A

#*b#*b >psonin phagocyte activation>psonin phagocyte activation hagocytosishagocytosis $actors and %$actors and %

#+a#+aBasophil and mast cells degranulation9 enhancedBasophil and mast cells degranulation9 enhanced

vascular permeability smooth musclevascular permeability smooth muscle

contractioncontraction

AnaphylaxisAnaphylaxis

(least potent)(least potent)

 #*a-%5A#*a-%5A

#+b#+b >psonin>psonin hagocytosishagocytosis #+-B and $actor %#+-B and $actor %

#:a#:a

Basophil and mast cells degranulation9 enhancedBasophil and mast cells degranulation9 enhanced

vascular permeability smooth musclevascular permeability smooth muscle

contractioncontraction

AnaphylaxisAnaphylaxis

(most potent)(most potent)

#*a-%5A#*a-%5A

#hemotaxis stimulation of respiratory burst#hemotaxis stimulation of respiratory burst

activation of phagocytes stimulation ofactivation of phagocytes stimulation of

inflammatory cyto2inesinflammatory cyto2ines%nflammation%nflammation

#:b#;#

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#omplement de$iciencies and disease#omplement de$iciencies and disease

Pathway,#omponentPathway,#omponent -isease-isease MechanismMechanism

#lassical Pathway#lassical Pathway  

#3%5#3%5 ereditary angioedemaereditary angioedema >verproduction of #8b (pro2inin)>verproduction of #8b (pro2inin)

  #3 #8 #+#3 #8 #+ redisposition to S/Eredisposition to S/E>psoni,ation of immune complexes help 2eep them soluble deficiency results in>psoni,ation of immune complexes help 2eep them soluble deficiency results in

increased precipitation in tissues and inflammationincreased precipitation in tissues and inflammation

Lectin PathwayLectin Pathway  

&B/&B/Susceptibility to bacterialSusceptibility to bacterial

infections in infants orinfections in infants or

immunosuppressedimmunosuppressed%nability to initiate the lectin pathay%nability to initiate the lectin pathay

!lternati"e Pathway!lternati"e Pathway  

$actors B or "$actors B or "Susceptibility toSusceptibility to

 pyogenic (pus-forming) pyogenic (pus-forming)

 bacterial infections bacterial infections/ac2 of sufficient opsoni,ation of bacteria/ac2 of sufficient opsoni,ation of bacteria

  #*#*Susceptibility to bacterialSusceptibility to bacterial

infectionsinfections/ac2 of opsoni,ation and inability to utili,e the membrane attac2 pathay/ac2 of opsoni,ation and inability to utili,e the membrane attac2 pathay

  #: #; #< #. and #=#: #; #< #. and #= Susceptibility to ?ram-Susceptibility to ?ram-negative infectionsnegative infections

%nability to attac2 the outer membrane of ?ram-negative bacteria%nability to attac2 the outer membrane of ?ram-negative bacteria

 roperdin (@-lin2ed)roperdin (@-lin2ed)SusceptibilitySusceptibility

meningococcalmeningococcal

meningitismeningitis/ac2 of opsoni,ation of bacteria/ac2 of opsoni,ation of bacteria

 $actors or %$actors or %#* deficiency and#* deficiency and

susceptibility to bacterialsusceptibility to bacterial

infectionsinfections6ncontrolled activation of #* via alternative pathay resulting in depletion of #*6ncontrolled activation of #* via alternative pathay resulting in depletion of #*

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CytokinesCytokinesCytokineCytokine

CytokineCytokine merupakan protein sekresi ke!il &an) berperan memediasimerupakan protein sekresi ke!il &an) berperan memediasidan pen)aturan imunitas, inflamasi dan hematopoiesis. Protein inidan pen)aturan imunitas, inflamasi dan hematopoiesis. Protein inidihasilkan ddihasilkan de novoe novo seba)ai respons stimulus imun.seba)ai respons stimulus imun.Fmumn&a berperan pada arak dekat dan mempun&ai half life &)Fmumn&a berperan pada arak dekat dan mempun&ai half life &)pendek dan terdapat dalam konsentrasi ke!il.pendek dan terdapat dalam konsentrasi ke!il.

Mereka bertindak den)an men)ikat reseptor spesifik pada membranMereka bertindak den)an men)ikat reseptor spesifik pada membran&) kemudian memberi sin&al pada sel itu melalui&) kemudian memberi sin&al pada sel itu melalui secondsecondmessengersmessengers, umumn&a t&rosine kinase, untuk men)ubah ekspresi, umumn&a t&rosine kinase, untuk men)ubah ekspresi)en)en

-espons thd !&tokine termasuk penin)katan atau penurunan-espons thd !&tokine termasuk penin)katan atau penurunanekspresi protein membran termasuk u)a reseptor !&tokine,ekspresi protein membran termasuk u)a reseptor !&tokine,proliferasi, dan sekresi effe!tor mole!ule..proliferasi, dan sekresi effe!tor mole!ule..

C&tokine merupakan nama umum dan serin) u)a disebutC&tokine merupakan nama umum dan serin) u)a disebutlymphokinelymphokine '!&tokines &) dibuat l&mpho!&te(,'!&tokines &) dibuat l&mpho!&te(, monokinemonokine '!&tokines dibuat oleh mono!&te(,'!&tokines dibuat oleh mono!&te(, chemokinechemokine '!&tokines d)n'!&tokines d)n!hemota!ti! a!ti0ities(, dan!hemota!ti! a!ti0ities(, dan interleukininterleukin '!&tokines dibuat oleh'!&tokines dibuat olehleuko!&te dan berperan thd leukosit lainn&a(. C&tokines dapatleuko!&te dan berperan thd leukosit lainn&a(. C&tokines dapatbekera pada sel &) men)hasilkann&a 'bekera pada sel &) men)hasilkann&a 'autocrine actionautocrine action(, pd sel(, pd sellain &) dekat 'lain &) dekat 'paracrine actionparacrine action(, atau pada sel lain &) letakn&a(, atau pada sel lain &) letakn&a

 auh dari tempat dihasilkan Lmelalui pemb.darah* ' auh dari tempat dihasilkan Lmelalui pemb.darah* 'endocrineendocrineactionaction(.(.

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Cytokine ActivitiesCytokine Activities

C&tokine a!ti0ities are !hara!teriAed usin)C&tokine a!ti0ities are !hara!teriAed usin)re!ombinant !&tokines and purified !ell populationsre!ombinant !&tokines and purified !ell populations inin

vitrovitro, or with, or with knock"out miceknock"out mice for indi0idual !&tokinefor indi0idual !&tokine)enes to !hara!teriAe !&tokine fun!tions)enes to !hara!teriAe !&tokine fun!tions in vivoin vivo..C&tokines are made b& man& !ell populations, but theC&tokines are made b& man& !ell populations, but thepredominant produ!ers are helper T !ells 'Th( andpredominant produ!ers are helper T !ells 'Th( andma!ropha)es.ma!ropha)es.

The lar)est )roup of !&tokines stimulates immune !ellThe lar)est )roup of !&tokines stimulates immune !ellproliferation and differentiation. This )roup in!ludesproliferation and differentiation. This )roup in!ludesInterleukin 'I%*(, whi!h a!ti0ates T !ells4 I%*K,Interleukin 'I%*(, whi!h a!ti0ates T !ells4 I%*K,whi!h stimulates proliferation of anti)en*a!ti0ated Twhi!h stimulates proliferation of anti)en*a!ti0ated Tand B !ells4 I%*", I%*N, and I%*O, whi!h stimulateand B !ells4 I%*", I%*N, and I%*O, whi!h stimulate

proliferation and differentiation of B !ells4 Interferonproliferation and differentiation of B !ells4 Interferon)amma 'I)(, whi!h a!ti0ates ma!ropha)es4 and I%*)amma 'I)(, whi!h a!ti0ates ma!ropha)es4 and I%*9, I%* and #ranulo!&te Mono!&te Colon&*Stimulatin)9, I%* and #ranulo!&te Mono!&te Colon&*Stimulatin)a!tor '#M*CS(, whi!h stimulate hematopoiesis.a!tor '#M*CS(, whi!h stimulate hematopoiesis.

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Selected +mmune Cytokines and Their %cti$ities;Selected +mmune Cytokines and Their %cti$ities;

CytokineCytokine &roducing Cell&roducing Cell Target CellTarget Cell 6unction;;6unction;;

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yy gg gg

#M*CS#M*CS Th !ellsTh !ells pro)enitor !ellspro)enitor !ells)rowth and differentiation)rowth and differentiation

of mono!&tes and DCof mono!&tes and DC

I%*I%*αα

I%*I%*ββ

mono!&tesmono!&tes

ma!ropha)esma!ropha)es

B !ellsB !ells

DCDC

Th !ellsTh !ells !o*stimulation!o*stimulation

B !ellsB !ells

maturation andmaturation and

proliferationproliferation

G !ellsG !ells a!ti0ationa!ti0ation

0arious0ariousinflammation, a!uteinflammation, a!ute

phase response, fe0erphase response, fe0er

I%*KI%*K Th !ellsTh !ellsa!ti0ated T and B !ells,a!ti0ated T and B !ells,

G !ellsG !ells)rowth, proliferation,)rowth, proliferation,

a!ti0ationa!ti0ation

I%*9I%*9Th !ellsTh !ells

G !ellsG !ells

stem !ellsstem !ells )rowth and differentiation)rowth and differentiation

mast !ellsmast !ells)rowth and histamine)rowth and histamine

releaserelease

I%*"I%*" ThK !ellsThK !ells

a!ti0ated B !ellsa!ti0ated B !ells

proliferation andproliferation and

differentiationdifferentiation

I)#I)# and I)7 s&nthesisand I)7 s&nthesis

ma!ropha)esma!ropha)es M3C Class IIM3C Class II

T !ellsT !ells proliferationproliferation

I%*NI%*N ThK !ellsThK !ells a!ti0ated B !ellsa!ti0ated B !ellsproliferation andproliferation and

differentiationdifferentiation

I)/ s&nthesisI)/ s&nthesis

I%*OI%*O

mono!&tesmono!&tes

ma!ropha)esma!ropha)es

ThK !ellsThK !ellsstromal !ellsstromal !ells

a!ti0ated B !ellsa!ti0ated B !ellsdifferentiation intodifferentiation into

plasma !ellsplasma !ells

plasma !ellsplasma !ells antibod& se!retionantibod& se!retion

stem !ellsstem !ells differentiationdifferentiation

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I%*8I%*8ma!ropha)esma!ropha)es

endothelial !ellsendothelial !ellsneutrophilsneutrophils !hemota2is!hemota2is

I%*1I%*1 ThK !ellsThK !ellsma!ropha)esma!ropha)es cytokine productioncytokine production

B !ellsB !ells a!ti0ationa!ti0ation

I%*KI%*Kma!ropha)esma!ropha)es

B !ellB !ellss

a!ti0ated T! !ellsa!ti0ated T! !ellsdifferentiation into CT%differentiation into CT%

'with I%*K('with I%*K(

G !ellsG !ells a!ti0ationa!ti0ation

I*I*αα leuko!&tesleuko!&tes 0arious0ariousviral replicationviral replication

M3C I e2pressionM3C I e2pression

I*I*ββ fibroblastsfibroblasts 0arious0ariousviral replicationviral replication M3C I e2pressionM3C I e2pression

I*I*γ γ Th !ells,Th !ells,

T! !ells, G !ellsT! !ells, G !ells

0arious0arious Viral replicationViral replication

ma!ropha)esma!ropha)es M3C e2pressionM3C e2pression

a!ti0ated B !ellsa!ti0ated B !ells I) !lass swit!h to I)#I) !lass swit!h to I)#KaKa

ThK !ellsThK !ells  proliferation proliferation

ma!ropha)esma!ropha)es patho)en eliminationpatho)en elimination

MIP*MIP*αα ma!ropha)esma!ropha)es mono!&tes, T !ellsmono!&tes, T !ells !hemota2is!hemota2is

MIP*MIP*ββ l&mpho!&tesl&mpho!&tes mono!&tes, T !ellsmono!&tes, T !ells !hemota2is!hemota2is

I%*I%*marrow stromamarrow stroma

th&mus stromath&mus stromastem !ellsstem !ells

differentiation intodifferentiation into

pro)enitor B and T !ellspro)enitor B and T !ells

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T#*T#*ββ T !ells, mono!&tesT !ells, mono!&tes

mono!&tes, ma!ropha)esmono!&tes, ma!ropha)es !hemota2is!hemota2is

a!ti0ated ma!ropha)esa!ti0ated ma!ropha)es I%* s&nthesisI%* s&nthesis

a!ti0ated B !ellsa!ti0ated B !ells I)/ s&nthesisI)/ s&nthesis

0arious0arious  proliferation proliferation

TTααma!ropha)es, mast !ells,ma!ropha)es, mast !ells,

G !ellsG !ells

ma!ropha)esma!ropha)esC/M and !&tokineC/M and !&tokine

e2pressione2pression

tumor !ellstumor !ells !ell death!ell death

T*T*ββ Th and T! !ellsTh and T! !ellspha)o!&tespha)o!&tes

pha)o!&tosis, @pha)o!&tosis, @

produ!tionprodu!tion

tumor !ellstumor !ells !ell death!ell death

7 )TL8 cytoto&ic T lymphocytes4 D)8 dendritic cells4 9M-)S:8 9ran%locyte-

Monocyte )olony Stim%latin" :actor4 IL8 interle%kin4 I:N8 Inter'eron4 T9:8

T%mor 9rowth :actor4 TN:8 T%mor Necrosis :actor

77 Italici1ed activities are inhi#ited

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@ther )roups of !&tokines in!lude interferons and@ther )roups of !&tokines in!lude interferons and!hemokines.!hemokines.

+nterferons+nterferons Ia and Ib inhibit 0irus repli!ationIa and Ib inhibit 0irus repli!ationin infe!ted !ells, while I) also stimulates anti)en*in infe!ted !ells, while I) also stimulates anti)en*presentin) !ell M3C e2pression.presentin) !ell M3C e2pression.

ChemokinesChemokines attra!t leuko!&tes to infe!tion sites.attra!t leuko!&tes to infe!tion sites.Chemokines ha0e !onser0ed !&steine residues thatChemokines ha0e !onser0ed !&steine residues thatallow them to be assi)ned to four )roups. Theallow them to be assi)ned to four )roups. The

)roups, with representati0e !hemokines, are C*C)roups, with representati0e !hemokines, are C*C!hemokines '-/T7S, MCP*, MIP*a, and MIP*b(,!hemokines '-/T7S, MCP*, MIP*a, and MIP*b(,C**C !hemokines 'I%*8(, C !hemokinesC**C !hemokines 'I%*8(, C !hemokines'%&mphota!tin(, and CC !hemokines'%&mphota!tin(, and CC !hemokines'ra!talkine(.'ra!talkine(.

Some !&tokines are predominantl& inhibitor&. orSome !&tokines are predominantl& inhibitor&. ore2ample, I%*1 and I%*9 inhibit inflammator&e2ample, I%*1 and I%*9 inhibit inflammator&!&tokine produ!tion b& ma!ropha)es. + to stimulate!&tokine produ!tion b& ma!ropha)es. + to stimulate!ellular immunit& and inflammation, and to!ellular immunit& and inflammation, and tostimulate B !ells to produ!estimulate B !ells to produ!e

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Cytokine ReceptorsCytokine Receptors

C&tokines a!t on their tar)et !ells b& bindin) spe!ifi! membrane re!eptors.C&tokines a!t on their tar)et !ells b& bindin) spe!ifi! membrane re!eptors.The 3elper T !ells ha0e two important fun!tions antibod&. Two fun!tionall&The 3elper T !ells ha0e two important fun!tions antibod&. Two fun!tionall&distin!t subsets of T !ells se!rete !&tokines whi!h promote these differentdistin!t subsets of T !ells se!rete !&tokines whi!h promote these different

a!ti0ities. Th !ells produ!e I%*K, I), and Tb, whi!h a!ti0ate T! anda!ti0ities. Th !ells produ!e I%*K, I), and Tb, whi!h a!ti0ate T! andma!ropha)es to stimulate !ellular immunit& and inflammation. Th !ellsma!ropha)es to stimulate !ellular immunit& and inflammation. Th !ellsalso se!rete I%*9 and #M*CS to stimulate the bone marrow to produ!ealso se!rete I%*9 and #M*CS to stimulate the bone marrow to produ!emore leuko!&tes. ThK !ells se!rete I%*", I%*N, I%*O, and I%*1, whi!hmore leuko!&tes. ThK !ells se!rete I%*", I%*N, I%*O, and I%*1, whi!hstimulate antibod& produ!tion b& B !ells.stimulate antibod& produ!tion b& B !ells.

T !ells are initiall& a!ti0ated as Th1 !ells, whi!h produ!e I%*K, I%*" andT !ells are initiall& a!ti0ated as Th1 !ells, whi!h produ!e I%*K, I%*" andI). The nearb& !&tokine en0ironment then influen!es differentiation intoI). The nearb& !&tokine en0ironment then influen!es differentiation into

Th or ThK !ells. I%*" stimulates ThK a!ti0it& and suppresses Th a!ti0it&,Th or ThK !ells. I%*" stimulates ThK a!ti0it& and suppresses Th a!ti0it&,while I%*K promotes Th a!ti0ities. Th and ThK !&tokines arewhile I%*K promotes Th a!ti0ities. Th and ThK !&tokines areanta)onisti! in a!ti0it&. Th !&tokine I) inhibits proliferation of ThK !ells,anta)onisti! in a!ti0it&. Th !&tokine I) inhibits proliferation of ThK !ells,while I) and I%*K stimulate B !ells to se!rete I)#Ka and inhibit se!retionwhile I) and I%*K stimulate B !ells to se!rete I)#Ka and inhibit se!retionof I)# and I)7. ThK !&tokine I%*1 inhibits Th se!retion of I) and I%*of I)# and I)7. ThK !&tokine I%*1 inhibits Th se!retion of I) and I%*K4 it also suppresses Class II M3C e2pression and produ!tion of ba!terialK4 it also suppresses Class II M3C e2pression and produ!tion of ba!terialkillin) mole!ules and inflammator& !&tokines b& ma!ropha)es. I%*"killin) mole!ules and inflammator& !&tokines b& ma!ropha)es. I%*"stimulates B !ells to se!rete I)7 and I)#. The balan!e between Th andstimulates B !ells to se!rete I)7 and I)#. The balan!e between Th andThK a!ti0it& ma& steer the immune response in the dire!tion of !ell*ThK a!ti0it& ma& steer the immune response in the dire!tion of !ell*mediated or humoral immunit&. re!eptors and their !orrespondin)mediated or humoral immunit&. re!eptors and their !orrespondin)!&tokines ha0e been di0ided into se0eral families based on their stru!ture!&tokines ha0e been di0ided into se0eral families based on their stru!tureand a!ti0ities.and a!ti0ities. 

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/L9%8% S+T7+0/L9%8% S+T7+0

-ematopoietin family-ematopoietin family re!eptors are dimers or trimersre!eptors are dimers or trimerswith !onser0ed !&steines in their e2tra!ellular domains andwith !onser0ed !&steines in their e2tra!ellular domains anda !onser0ed Trp*Ser**Trp*Ser seuen!e. 72amples area !onser0ed Trp*Ser**Trp*Ser seuen!e. 72amples arere!eptors for I%*K throu)h I%* and #M*CS.re!eptors for I%*K throu)h I%* and #M*CS.+nterferon family+nterferon family re!eptors ha0e the !onser0ed !&steinere!eptors ha0e the !onser0ed !&steineresidues but not the Trp*Ser**Trp*Ser seuen!e, andresidues but not the Trp*Ser**Trp*Ser seuen!e, andin!lude the re!eptors for Ia, Ib, and I).in!lude the re!eptors for Ia, Ib, and I).

Tumor 0ecrosis 6actor familyTumor 0ecrosis 6actor family re!eptors ha0e fourre!eptors ha0e foure2tra!ellular domains4 the& in!lude re!eptors for solublee2tra!ellular domains4 the& in!lude re!eptors for solubleTa and Tb as well as membrane*bound CD"1Ta and Tb as well as membrane*bound CD"1'important for B !ell and ma!ropha)e a!ti0ation( and as'important for B !ell and ma!ropha)e a!ti0ation( and as'whi!h si)nals the !ell to under)o apoptosis(.'whi!h si)nals the !ell to under)o apoptosis(.

Chemokine familyChemokine family re!eptors ha0e se0en transmembranere!eptors ha0e se0en transmembraneheli!es and intera!t with # protein. This famil& in!ludesheli!es and intera!t with # protein. This famil& in!ludesre!eptors for I%*8, MIP* and -/T7S. Chemokinere!eptors for I%*8, MIP* and -/T7S. Chemokine

re!eptors CC-N and CC-" are used b& 3I tore!eptors CC-N and CC-" are used b& 3I topreferentiall& enter either ma!ropha)es or T !ells.preferentiall& enter either ma!ropha)es or T !ells.

/T/#@IS SIT@GI 4/T/#@IS SIT@GI 4

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/T/#@IS SIT@GI 4/T/#@IS SIT@GI 4

C&tokine a!ti0it& !an be blo!ked b&C&tokine a!ti0it& !an be blo!ked b& antagonistsantagonists,,mole!ules whi!h bind !&tokines or their re!eptors.mole!ules whi!h bind !&tokines or their re!eptors.

I%* has a spe!ifi! anta)onist that blo!ks bindin)I%* has a spe!ifi! anta)onist that blo!ks bindin)of I%*a and I%*b to their re!eptor.of I%*a and I%*b to their re!eptor.

Durin) immune responses, fra)ments ofDurin) immune responses, fra)ments ofmembrane re!eptors ma& be shed and thenmembrane re!eptors ma& be shed and then!ompete for !&tokine bindin).!ompete for !&tokine bindin).

Mi!robes also influen!e !&tokine a!ti0ities. orMi!robes also influen!e !&tokine a!ti0ities. ore2ample, a!!inia 0irus 'Smallpo2 and Cowpo2(e2ample, a!!inia 0irus 'Smallpo2 and Cowpo2(en!odes soluble mole!ules whi!h bind I), whileen!odes soluble mole!ules whi!h bind I), while7pstein*Barr 0irus 'Infe!tious Mononu!leosis(7pstein*Barr 0irus 'Infe!tious Mononu!leosis(

en!odes a mole!ule homolo)ous to I%*1 thaten!odes a mole!ule homolo)ous to I%*1 thatsuppresses immune fun!tion in the host.suppresses immune fun!tion in the host.

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The T re!eptor famil& mole!ules CD"1 and asThe T re!eptor famil& mole!ules CD"1 and asbind !ell surfa!e li)ands on effe!tor T !ells+ CD"1%bind !ell surfa!e li)ands on effe!tor T !ells+ CD"1%and as%. CD"1 is e2pressed on B !ell andand as%. CD"1 is e2pressed on B !ell and

ma!ropha)e plasma membranes.ma!ropha)e plasma membranes.T !ell CD"1% bindin) to B !ell CD"1 stimulates B !ellT !ell CD"1% bindin) to B !ell CD"1 stimulates B !ellproliferation and isot&pe swit!hin). T !ell CD"1%proliferation and isot&pe swit!hin). T !ell CD"1%bindin) to ma!ropha)e CD"1 stimulatesbindin) to ma!ropha)e CD"1 stimulatesma!ropha)es to se!rete Ta and be!ome mu!hma!ropha)es to se!rete Ta and be!ome mu!h

more sensiti0e to I). T !ell as% bindin) to asmore sensiti0e to I). T !ell as% bindin) to asleads to the a!ti0ation of !aspase proteases thatleads to the a!ti0ation of !aspase proteases thatinitiate apoptosis of the !ell e2pressin) membraneinitiate apoptosis of the !ell e2pressin) membraneas.as.

/!ti0ated l&mpho!&tes e2press as, so that as%*/!ti0ated l&mpho!&tes e2press as, so that as%*

positi0e T! !ells !an re)ulate the immune responsepositi0e T! !ells !an re)ulate the immune responseb& eliminatin) a!ti0ated !ells. /n immune defi!ien!&b& eliminatin) a!ti0ated !ells. /n immune defi!ien!&disease linked to e2pression of a mutant as isdisease linked to e2pression of a mutant as is!hara!teriAed b& o0er*proliferation of l&mpho!&tes.!hara!teriAed b& o0er*proliferation of l&mpho!&tes.

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