Immunologi Dasar Loly

8/12/2019 Immunologi Dasar Loly

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IMUNOLOGI DASAR

Loly R D Siagian



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Sejarah Imunologi

Louis Pasteur : the Father of immunology Edward jenner, 1796 :

Mengumpulkan nanah dari luka pox sapi dari tangan

pemerah susu nanah tsb diinokulasikan ke seorang

anak 4 thn anak hanya panas tp tdk timbul sakit. Anan tsb mendapat inokulasi nanah dari cacar aktif

tdk timbul reaksi yg berarti

George Kohler. 1975 :

Memproduksi Ab monoklonal dgnhibridisasi sel mutan

mieoloma dgn sel B yg memproduksi Ab (teknis

hibridoma).

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Imunitas

Imunitas :resistensi thd penyakit terutama penyakit infeksi

Sistem imun :

Gabungan sel, molekul, dan jaringan yg berperan

dlm resistensi thd infeksi tsb.

Respon Imun :

Reaksi yg dikoordinasi oleh sel-sel, molekul-

molekul

thd mikroba & bahan lainnya.

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Bahasan

Konsep Imunitas

Imunitas Alamiah (Innate) Immunity

Imunitas Didapat (Adaptive) Immunity_



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Imunitas

Asal : perlindungan thd tuntutan legal senatorRomawi pd masa pemerintahannya

Def : perlindungan thd penyakit, khususnya

peny.infeksi

Sistem imun : kumpulan sel & molekul ygbertanggung jawab thd imunitas

Fx fisiologis : pertahanan thd mikroba infeksius (&

substansi asing non infeksius)



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Peran Sistem Imun

Role of the immun system Implications

Defense against infections Deficiency immunity result in

increased susceptibility to infections

Vaccination boost immun defenses &

protect against infection

The immun system recognizes &

responds to tissue grafts & newly

introduced proteins

Immune responds are important

barriers to transplantation & gene

therapy

Defense against tumors Potential for immunotherapy of

cancer Antibodies are highly spesific reagents for

detecting any class of molecules

Immunologic approaches for

laboratory testing are widely used in

clinical medicine & research



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Sistem Imun

Imunitas alamiah (Innate / Natural / NativeImmunity)

Pertahanan lini pertama thd mikroba

Tdd pertahanan seluler & biokimia utk berespon scr

cepat thd mikroba, bahkan sblm infeksi Bereaksi lgsg thd mikroba atau hsl produksi injury cell

Berespon sama thd infeksi yg berulang

Imunitas didapat (Adaptive / Spesific Immunity)

Distimulasi oleh paparan agent infeksius, kemampuan

& pertahanannya meningkat pd setiap paparan

Karakteristik .....



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Karakteristik : Sangat spesifik utk molekul yg berbeda

Memiliki kemampuan utk mengingat & merespon yg >>

thd paparan berulang mikroba yg sama.

Memiliki kemampuan membedakan mikroba & molekul(spesifik)

Memiliki kemampuan protektive yg didapat dr

pengalaman pertama (didapat)



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Gambaran Innate & Adaptive Immunity

INNATE ADAPTIVECHARACTERISTIC

Spesificity

Diversity

MemoryNonreactivity to self

For structured shared by groups of

related mickrobes

Limited, germline encoded

NoneYes

For antigens of microbes & for nonmicrobial Ag

Very large, receptor are produced by somatic

recombination of gene segments

YesYes

COMPONENTS

Cellular & chemical

barriers

Blood protein

Cells

Skin, mucosal epithelial, antimicrobial

chemicals

Complement, others

Phagocytes (Macrophage, neutrophil,

NK cells)

Lynphocytes in epithelia, Ab secreted at

epithrlial surface

Antibodies

Lymphocytes



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Imunitas Alamiah

Fx : Sbg respon inisial utk mikroba (mencegah, mengontrol,

mengeliminasi infeksi pd host)

Menstimulasi /mempengaruhi respon imun didapat spy

optimal Komponen :

Barrier fisik & kimia : epitel, substansi antimikroba

Sel fagositik (sel NK)

Protein darah (sistem komplemen, mediator inflamasi)

Sitokin (regulasi & koordinasi aktifitas imun.alamiah)



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Mengenali struktur karakteristik mikroba patogen Substansi mikroba yg menstimulasi imun.alamiah :

PAMPs (pathogen associated molecular patern)

Reseptor yg terikat pd PAMPs : patern recognition

receptors Kelas mikroba berbeda PAPMs berbeda

Spesificity: dpt mengenali self & nonself

Mengenali produk mikroba yg penting utk survive

mikroba (c/ ds viral RNA, LPS, teicnoic acid) Kdg mikroba mengalami mutasi atau kehilangan Ag yg

dikenali adaptive

Gambaran utama Imunitas alamiah



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Memiliki patern recognition molecules, tdd :

Cell-associated patern recognition receptor (permukaan & dlm sel)

Soluble protein dlm darah & cairan ekstrasel

Patern recognition receptors dikode pd germline DNA

Shg spesifisitas terbatas, hanya mengenali 103 patern mikroba

Hny dpt membedakan kelas mikroba berbeda

Mengenali sel host yg stress/injury :

c/ Heat shock protein (HSP)

Class I MHC-like molecul

Altered membrane phospholipids



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Komponen

Imunitas Alamiah



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Fagosit & respon inflamasi Neutrophils : bermigrasi ke tempat infeksi bbrp jam stlh

masuknya mikroba

Sistem Fagosit mononuklear : kumpulan sel yg

berfungsi fagositosis, punya peranan penting dlmimunitas alamiah & didapat



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Rekrutment lekosit ke tempat infeksi :

Selectin-mediated roling of leucocyte on endothelium Result: leucocytes repetitively detach & bind & roll along the endothelial surface

Chemokine-mediated increase in affinity of integrins Fx chemokine : stimulate chemotaxis of cells

Stable integrin-mediated adhesion of leucocytes to endothelium Result: leucocytes attach firmly to the endothelium, their cytoskleton is reorganized,

spread out on the endothelium surface

Transmigration of leucocytes through the endothelium Stimulate the cells to migrate through interendothelial spaces along the chemical

concentration

Akumulasi leukosit di jaringan adlh sbg komponen utama inflamasi



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Rekrutmen Leukosit



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Sistem komplemen :

Tdd bbrp protein plasma yg diaktivasi oleh mikroba

Berfungsi : meningkatkan destruksi mikroba daninflamasi

Pengenalan mikroba oleh komplemen tjd dlm 3 jalur :

Jalur klasik :

Ditemukan 1x

Menggunakan C1 utk deteksi antibodi IgM, IgG1dan IgG3 yg

terikat pd permukaan mikroba atau struktur lainnya

Jalur alternatif :

Distimulasi oleh pengenalan langsung struktur permukaan

mikroba

Jalur lectin :

Distimulasi protein plasma mannosa binding lectin (MBL) yg dpt

mengenali residu terminal manosa pd glikoprotein &glikolipid

mikroba



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Jalur Aktivasi Komplemen



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Sitokin : Menarik & mengaktivasi leukosit dan perubahan

produksi sistemik

Meningkatkan sintesis sel efektor & protein yg

mempotensiasi respon antimikroba Sumber sitokin : makrofag, neutrofil, sel NK, sel

endotel, bbrp sel epitel

Pd imun.didapat : sitokin berfungsi

mengkomunikasikan informasi diantara sel inflamasidan sel inflamasi & sel jaringan respon (spt sel endotel

veskular)



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Imunitas Didapat

Terdiri dr 2 tipe : Imunitas humoral :

Dimediasi oleh molekul dlm darah & sekresi mukosa (Antibodi)

yg diproduksi limfosit B (sel B)

Pertahanan thd mikroba ekstrasel & toksinnya (Ab berikatan

dgn mikroba & toksin)

Imunitas cell-mediated (seluler)

Dimediasi oleh limfosit T (sel T)

Pertahanan thd mikroba intrasel (virus, bakteri).



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Gambaran utama Imunitas didapat

Feature Funct io nal signi f icance for Imm uni ty to micro bes

Spesificity

Diversity

Memory

Clonal expansion

Specialization

Contraction &

Hoemastasis

Nonreactivity to self

Ensure that distinct microbes elicit spesific respons

Enables immun system to respon to a large variety of antigens

Leads to enhance responses to repeated exposures to the same

antigens

Increases number of antigen-spesific lymphocytes to keep pace with

microbes

Generated responses that are optimal for defense against different type

of microbes

Allows immun system to respon to newly encountered antigens

Prevents injury to the host during respons to foreign antigens



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Specificity & diversity : Antigen berbeda utk porsi yg berbeda ( single complex

protein, polisakarida, molekul lain)

Bagian dr antigen yg dikenali oleh limfosit disbt epitope

/ determinant Limfosit mengekspresikan reseptor membran yg dpt

membedakan perbedaan struktur Ag.

Lymphocyte repertoire : kapasitas limfosit mengenali

Ag yg berbeda (± 10

7

-10

9

determinan Ag yg berbeda) Memory :

Sbg respon thd paparan sekunder thd Ag yg sama



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Clonal expansion : Limfosit berproliferasi pd paparan Ag

Peningkatan jumlah sel yg mengekspresikan reseptoridentik thd Ag & membentuk suatu klon

Spesialization : Kelas mikroba yg berbeda, mikroba yg sama dgn

stage infeksi yg berbeda (intrasel & ekstrasel).

Nonreactivity to self : Immunilogical unresponsiveness : Tolerance

Abnormalities in the induction or maintenance of selftolerance immune respons against self antigens Autoimmun disease



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Komponen Seluler Imun.didapat

Limfosit

APC (Antigen Presenting Cells)

Sel efektor



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Limfosit

Sel yg dpt mengenali & berespon thd Ag, sbg mediator imunitas humoral& seluler

Jenis limfosit (gambar)

Limfosit B : Mengenali Ag ekstrasel (tmsk permukaan sel)

Berdiferensiasi mnjd Ab-secreting plasma cell (mediator humoral)

Limfosit T : Mengenali Ag dr mikroba intrasel

Berfungsi menghancurkan mikroba & sel yg terinfeksi

Hanya mengenali peptida Ag yg melekat pd protein host (MHC), ygdiekspresikan pd permukaan sel lain

Hanya mengenali & berespon thd permukaan sel , bukan Ag soluble

Tdd : Helper T lymphocyte, Cytotoxic T lymphocyte (CTL)

Natural Killer cells (NK cells) Thd virus, mikroba intrasel

Pembagian kelas limfosit lain : mnrt ekspresi protein pemukaan“molekul CD”



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Immunologi Dasar Loly

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