kul. sistem imun, blok alergi (2)

7/29/2019 Kul. Sistem Imun, Blok Alergi (2)

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IMUNOLOGI DASAR

SISTEM IMUN

Oleh :

T. Husni T.R,dr.,M.kes.,SpTHT-KL


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SISTEM IMUN

NON SPESIFIK

IMUN SPESIFIK

ORGANLIMFID

PERTAHANAN FISIK/MEKANIK

PERTAHANAN BIOKIMIA

PERTAHANAN HUMORAL

KOMPLEMEN

INTERPERON

CRP

PERTAHANAN SELULERFAGOSIT

MAKOFAG

LGL

SISTEM IMUN SPESIFIK HUMORAL

SISTEM IMUN SPESIFIK SELULER

ORGANLIMFID PRIMER

ORGANLIMFID SKUNDER


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Pembagian sistem kekebalan

tubuh manusia

1. Kekebalan tubuh yg. tdk. spesifik:

- Fisik : kulit, sel. Lendir- Kimiawi : enzim, asam lambung- Mekanik : gerak perist.usus, rambutgetar sel. lendir

- Fagositosis- Komplemen


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Kekebalan tubuh spesifik

- Kekebalan didapat- Perlu pengenalan- Diperankan oleh kekebalan humoral

dan selular yg. saling berinteraksi


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1. Sel-sel yg. berperan padasistem kekebalan tubuh

Sel limfosit : Sel T dan Sel BSel T : - Sel T helper ( sel T4)

- Sel T supressor( sel T8)

Sel limfosit non T, non B: selNatural Killer ( sel NK)


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2. Sel fagosit ( sel penghancurmikroba- Sel neutrofil (leukosit berinti banyak)- Sel eosinofil : berperan pada inf.

parasit serta pada reaksi alergi

- Sel monosit/makrofag : berinti sat

3. Sel basofil dan sel mast

Mengandung zat histamin dll.Berperan pada reaksi peradangan dan reaksialergi


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Komponen sistem kekebalan tubuh

A. Sistem kekebalan humoralTerdiri dari 5 jenis antibodi :Ig M, G, A, E dan D

- Imunoglobulin M :Berperan pada reaksi kekebalan awal mis.

Inf. Tahap awal. Tidak dapat melaluiplasenta


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-Imunoglobulin G:Berperan pada reaksi kekebalansekunder (lanjutan)

- Imunoglobulin A :Pada perm. sel. lendir mis.sal. cerna(IgA sekretorik) atau sal. napas


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-Imunoglobulin E:Menempel pada sel mast (berperan padareaksi peradangan/ alergi ), bekerja samadengan sel eosinofil menghancurkan

parasit

-Imunoglobulin D :

Kadarnya sangat kecil, fungsi belum jelas


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B. Sistem kekebalan selular(Cell

Mediated Immunity/ CMI):- Diperankan oleh sel T danmonosit/ makrofag- Kontak antar sel melalui sitokin- Berperan pada infeksi kronikterutama infeksi kuman dalam selmis. Tbc, virus serta jamur


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C.Proses fagositosis Tiga tahap :1. Pergerakan leukosit ke tempatkuman berada2.Pengikatan kuman oleh antibodi(opsonisasi)3.Pengeluaran enzim oleh leukosituntuk menghancurkan kuman ygsudah ditelan


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D. Sistem komplemen- Memperkuat pertahanan tubuhspesifik dan non spesifik.

- Diaktifkan melalui jalur klasikdan jalur alternatif.


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IMUNITAS INATE DAN ADAPTIF

Im. inatte=natural=nativeSudah ada sebelum infeksiBereaksi thd mikroba

Reaksi berulang juga terjadi1.Barier fisika dan kimiawi, sel epitel,antimikroba yg diproduksi di permk. Epith

2.Sel fagosit: netrofil, makrofag, sel NK

3.Sistem komplemen, mediator inflamasi4.Sitokin:regulasi dan koordinasi aktivitas

sel inate


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Imunitas adaptif

Imunitas timbul setelah ada infeksiSifat spesifik terhadap mikrobaTimbul sel memori, yg akan berperan pada

infeksi berikutnya

Sel limfosit T dan B serta komponennya

Kerja sama antara respon im.inate danim.adaptif


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Imunitas adaptif

Im.humoral , sel limf B mensekresi Ab utkmemusnahkan Ag ekstraselularIm. Selular,sel limf T atau sel makrofag

aktif akan memusnahkan mikroba yg sudahdifagositosis atau sel yg sudah terinfeksi


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Spesifisitas dan sel memori

Antigen A dan B akan memproduksi Abspesifik untuk masing-masing Ag

Respons sekunder thd Ag A terjadi > cepatdan > banyak dp respons primerdisebabkan oleh adanya sel memori A

Kadar Ab akan ber< dengan perjalanan

waktu


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Sel limfosit

Sel limf B akan mengenal Ag dan Ab

Sel limf Th mengenal Ag ygdipresentasikan dipermukaan sel pejamu

(host) sitokin yg akan mengaktifkan sellimf T dan sel B (proliferasi dandiferensiasi); aktifasi makrofag; inflamasi

Sel limf sitolitik mengenal Ag pd sel targetlisis

Sel Natural killer(NK) dg reseptornyamelisis sel target


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Fase respons imun adaptif

Terdiri dari 3 fase:

1. Fase pengenalan Ag

2. Fase aktivasi sel limfosit3. Fase efektor, pemusnahan Ag

Respons imun akan ber < bila sel sudahdi eliminasi (apoptosis) sedangkan selmemori bertahan


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Hipotesis seleksi klonal

Setiap Ag A atau B akan memilih klon sellimfosit dan berproliferasi dan diferensiasiklon


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Aktivas sel limfosit

Signal 1:Mikroba memproduks Ag yg dikenalsel limfosit spesifik

Signal 2: Mikroba, endotoksin akan terikatpd reseptor pd sel asesori ( sel makrofag)dan akan sitokin (Bagian dari respon im

inate)

Sel limfosit berproliferasi dan diferensiasi


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Respons sel limfosit

Sel limf naiv akan berespons thd Ag,proliferasi sel dan diferensiasi ke sel efektordan sel memori Kemudian terjadi

homeostasis o.k sel limfosit aktif akanmusnah (apoptosis)


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COMPLEMENT SYSTEM

IN IMMUNE RESPONSE


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DEFINITION

Complement is a collective termtodesignate a group of plasma and cellmembrane proteins that play a key role

in the host defense process

Cascade of serum proteins (designated

C1-C9)that can form a membrane attackcomplex(MAC) capable of lysingcellular & bacterial (particularly Gramnegative) membranes


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DEFINITION

Mostly made in the liver and exist as aninactive proenzymes that arecleaved to generate the active enzyme

componentsComplement components are produced

by: liver (parenchyma),macrophages,monocytes, GI and urinary tract,neutrophils


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Inactivation of Complement

Inactivated (destroyed) by heating serum at56 C for 30 minutes

(antibodies not destroyed at thistemperature)


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NOMENCLATURE

Complements consists of >25 proteinsdesignated by:

1. Numbers

following the letter C (complement)C1 to C9 (classic pathway)

2. Letter

Factor B, D, H, and I (alternativepathway)


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COMPLEMENT ACTIVATION

Classic pathway

Can be activated by antibody ormolecules such as MBL (an acute phaseprotein that binds mannose and is

structurally similar to C1q) bound tobacteria


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Alternative pathway

Alternative pathway is independent of

antibody and can occurs when C3b binds to:bacterial membranes, some viruses, yeast,fungus, helminths, tumor cell membranes,aggregated immunoglobulins


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Both pathways proceed by means ofsequential activation and assembly of aseries of proteins, leading to the formation

of a complex enzyme capable of bindingand cleaving a key protein, C3.

C3 is common to both pathways


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Thereafter, the 2 pathways proceedtogether through binding of the terminalcomponents to form a membrane attack

complex (MAC)

ultimately caused CELL LYSIS

Mechanism of Action: Complement


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Mechanism of Action: Complement

Bacterium

Fcantibody

antigen F(ab)2

C1r C1s

C1qC1

Bacterium

Step 1

C4

C4a

C4b

C2C1

C4b2b

C4b2b Complex

( C3/C5 convertase)

Step 2

C2a

C4bBacterium Bacterium

Note: a is a smaller fragment, while b is a larger fragement

Mechanism: (cont)Alternative Pathway


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(C4b2b)

C3C3a

C3b

C3b

( Binds to several C3)

C3b C5b

C5

C5a

C5b

Step 3Step 4

Bacterium

Lysis

Step 5

C5b

C6

C7C8

C9

Terminal Pathway (Classical and alternative Pathway)

ec a s (co t)

C3bC5

also activates C3

Bacterium

Bacterium

Bacterium

Bacterium

C3C5

Convertase

Alternative Pathway:


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Alternative Pathway:

C3bC3

HC3bH

Inactivation

Terminal Pathway

Lysis

B

C3bB

Activation

C3 convertase

P (properdin)

C3bBb

D

Ba


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Complement Cascade Activation


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ROLE OF COMPLEMENT


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ROLE OF COMPLEMENT

1. Formation of MAC (Membrane AttackComplex) that lyses gram negative bacteria;

viruses and cells.

2. Potentiation of inflammation


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C3a

C5aAnaphylatoxin

Mast cell

- Cause smooth muscle ( lung

and intestinal wall) to contract.

- Mast cells degranulate releasing

vasoactive amines.

- Vascular permeabilty resulting inEDEMA.


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ROLE OF COMPLEMENT

3. Chemoattractant/Chemotaxis

C5a- attracts all types of phagocytic

cells. (Neutrophils, Eosinophils,Macrophages, Basophils)

C5b67- Neutrophils, Eosinophils


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ROLE OF COMPLEMENT

4. Enhances Uptake (Opsonization)

by phagocytic cells (C3b and C4b)

A complement component, C3b,embeds itself on the surface of theinvading microbe, and allows it tobecome bound to C3b receptors onphagocytes

Opsonization/Phagocytosis


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Opsonization/Phagocytosis

Bacteria Binding

Complement

(ie. C3b)

Macrophage

(with receptor

for C3b)

** Phagocytic cells bear C3b receptor

and FC receptor efficient phagocytosis


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Deficiency of Complement

C3

C5,C6,C7

Severe Pyogenic Infection[ Example. Brittany Spaniel ]

-Immunecomplex deposition

(Lupus-like disease) affecting joints

and kidneys.

Recurrent infection, Lysis?

CONCLUSION


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CONCLUSION

The complement system consists of aseries of proteins that work to"complement" the work of antibodies in

destroying bacteria.

Complement proteins circulate in theblood in an inactive form.


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CONCLUSION

The so-called "complement cascade"set off when the first complementmolecule, C1, encounters antibody

bound to antigen in an antigen-antibody complex. Each of thecomplement proteins performs itsspecialized job in turn, acting on themolecule next in line.


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CONCLUSION

The end product is a cylinder that

punctures the cell membrane and, byallowing fluids and molecules to flow inand out, dooms the target cell


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kul. sistem imun, blok alergi (2)

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