1 IMUNOLOGI DASAR Loly R D Siagian
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 1/35
1
IMUNOLOGI DASAR
Loly R D Siagian
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 2/35
2
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 3/35
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).
3TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 4/35
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.
4TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 5/35
5TR_imun1_loly
Bahasan
Konsep Imunitas
Imunitas Alamiah (Innate) Immunity
Imunitas Didapat (Adaptive) Immunity_
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 6/35
6TR_imun1_loly
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)
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 7/35
7TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 8/35
8TR_imun1_loly
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 .....
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 9/35
9TR_imun1_loly
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)
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 10/35
10TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 11/35
11TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 12/35
12TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 13/35
13TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 14/35
14TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 15/35
15TR_imun1_loly
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)
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 16/35
16TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 17/35
17TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 18/35
18TR_imun1_loly
Komponen
Imunitas Alamiah
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 19/35
19TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 20/35
20TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 21/35
21TR_imun1_loly
Rekrutmen Leukosit
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 22/35
22TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 23/35
23TR_imun1_loly
Jalur Aktivasi Komplemen
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 24/35
24TR_imun1_loly
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)
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 25/35
25TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 26/35
26TR_imun1_loly
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).
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 27/35
27TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 28/35
28TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 29/35
29TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 30/35
30TR_imun1_loly
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
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 31/35
31TR_imun1_loly
Komponen Seluler Imun.didapat
Limfosit
APC (Antigen Presenting Cells)
Sel efektor
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 32/35
32TR_imun1_loly
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”
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 33/35
33TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 34/35
34TR_imun1_loly
8/12/2019 Immunologi Dasar Loly
http://slidepdf.com/reader/full/immunologi-dasar-loly 35/35
35TR i 1 l l