immunokimia - 2
TRANSCRIPT
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IMUNOKIMIA
Nurlaely Mida Rachmawati
FK-UPN “VETERAN” JAKARTA
21 OKTOBER 2005
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IMUNITAS
Lingkungan TIDAK Steril
Tubuh punya mekanisme pertahanan
KEBAL terhadap infeksi (Latin: immunitas = kebal dari)
Proses mekanisme pertahanan tubuh
IMUNOLOGI
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JALAN MASUK INFEKSIInfeksi terjadi saat patogen/antigen masuk ke dalam tubuh & melakukan multiplikasi
Makanan dan air
-cacing parasit, demam tifoid
-amoeba disentri dll
Gigitan serangga
-protozoa malaria, demam berdarah
Luka terbuka
-tetanus
Hub. Seksual
-virus HIV, Herpes genital
-bakteri gonorrhea
-spirochaeta sipilis
Infeksi butiran/droplet
-Virus influensa, bakteri pneumonia
-Bakteri dipteri, bakteri TBC dll.
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Variasi ukuran bakteri
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Barier non spesifik
MATA (airmata, lisosim)
PHARYNX (bakteri)
KULIT (Barier fisik, kelenjar sebaceous, bakteri)
LAMBUNG (pH asam)
DUODENUM (pH alkali)
KOLON (bakteri)
KANTUNG KEMIH (flushing)
VAGINA (pH asam)
Trachea (mukus, cilia)
Rongga Hidung (mukus)
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IMUNITAS
Dibagi menjadi 2 macam, a.l: Alami/non spesifik
Humoral: Komplemen, Interferon, CRP Seluler : - Fagosit (mononuklear & PMN) - Sel NK - Sel Mast
- Basofil Dapatan/Spesifik
Humoral: Sel B (IgD, IgM, IgG, IgE, IgA) Seluler : Sel T (Th, Ts, TC, TCTL)
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A n t I g e n
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DEFINISI Patogen = Antigen Antigen ≠ Patogen PATOGEN =
Sesuatu yang dapat menyebabkan penyakit
ANTIGEN/IMUNOGEN = Sesuatu yang dapat menginduksi sistem
kekebalan tubuh
Contoh: Patogen = mikroorganisme Antigen = mikroorganisme + Harmless (serbuk sari, alergen)
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SIFAT ANTIGEN
Ukuran molekul bersar (BM > 10.000 dalton) Strukturnya kompleks (Misal: protein) Mudah kontak dengan Sistem imun Asing
IMUNOGENISITAS ditentukan oleh: Sifat antigen Spesies Jalan masuk Kepekaan metoda deteksi
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DETERMINAN ANTIGEN (Ag) EPITOP/Determinan antigen:
Bagian antigen yang kontak dengan daerah paratop
PARATOP: Daerah hipervariabel pada antibodi yang
berkontak dengan epitop
Jumlah epitop ditentukan oleh: 1. Ukuran Ag
Ovalbumin (BM= 42.000 dalton 5 epitop) Tiroglobulin (BM= 700.000 dalton ± 40 DA)
2. Kompleksitas Glikolipid lebih imunogenik daripada Lipoprotein lipid murni
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Pembagian Ag JENIS CONTOH
UnideterminanUnivalen
UnideterminanMultivalen
MultideterminanUnivalen
MultideterminanMultivalen
H A P T E N
POLISAKARIDA
P R O T E I N
Zat kimia kompleks
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H A P T E N
Adalah: Molekul kecil non imunogenik yang
dapat menginduksi respon imun bila diikatkan dengan makromolekul (sebagai Carier)
Contoh: RNA, DNA
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ANTIBODI ADALAH:
Glikoprotein yang dihasilkan untuk merespon Ag secara spesifik
Jenis ikatan dengan Ag = NON KOVALEN
STRUKTUR Terdiri atas:
2 rantai BERAT (H=Heavy) 4 polipeptida
2 rantai RINGAN (L=Light) berbentuk Y
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STRUKTUR
Rantai H (CH2) mengikat OLIGOSAKARIDA melalui ikatan N-glikosidik
Unit KH: manosa, galaktosa,fruktosa, asetil-
neuramin, glukosamin.
DAERAH 1. konstan/C (CH & CL)
2. Variabel/V (VH & VL) 3. Hipervariabel
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ANTIBODI
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Daerah HIPERVARIABEL
CDR: Complementary Determining Regions
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BINDING SITE
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Kelas Utama Ig Manusia
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Klasifikasi Antibodi
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Antibodi sekretori (sIgA)
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Perkembangan IgG Plasenta
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IgG kolostrum
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Definisi
Reaksi Ag – Ab RESPON IMUN Respon imun adalah:
Respon sistem kekebalan akibat terjadi ikatan Ag – Ab (kompleks imun)
Macam-macam ikatan Ag-Ab (non-kovalen): Ikatan ion Ikatan hidrogen Ikatan hidrofob Ikatan Van der Waals
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Ikatan ION & Ikatan HIDROGEN
Ikatan ION
Ikatan HIDROGEN
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Ikatan HIDROFOB & VEN Der WAALS
Ikatan HIDROFOB
Ikatan VAN der WAALS
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AVINITAS & AVIDITAS AVINITAS = kekuatan ikatan (Ag-Ab) Reaksi: Ab + H AbH Ka = [AbH]/[Ab][H]
Avinitas = Ka
AVIDITAS = afinitas fungsional (efek BONUS)
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Efek BONUS
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HUMORAL
Sistem KOMPLEMEN Adalah Protein serum (9 macam:C1-C9) Jumlah ± 20 buah Peran:
Lisis sel (fiksasi,opsonisasi, inflamasi) Inflamasi (sinyal)
Sintesis: HATI & makrofag Ada 2 jalur aktifasi:
1. Jalur KLASIK/antibody dependent 2. Jalur ALTERNATIF/antibody independent
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Komponen Protein Komplemen
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Jalur KLASIK & Jalur ALTERNATIF
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Membrane Attack Complex (MAC)
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SELULER -Fagositosis
Jalur mikroba oksodatif di NEUTROFIL
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SEL EFEKTOR
Monosit – esterase non spesifik
4 neutrofil -1 eusinofil
makrofag
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FAGOSITOSIS
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HUMORAL – Sel B Teori pembentukan Ab
1. Teori INSTRUKTIF (L.Pauling, 1940) Ag = cetakan
2. Teori SELEKSI (M Burnet, N Jerne, D Talmage, J Lederberg, 1950-an)
Combining site Ab SUDAH ADA sebelum bertemu Ag
KESIMPULAN: 1. 1 jenis Ab dibentuk dari 1 klon sel Pasma 2. Spesifisitas Ab ditentukan oleh urutan asam
aminonya 3. Ab bersifat Self Tolerant 4. Suatu klon TETAP ADA, walaupun tidak bertemu
dengan Ag SEL MEMORI
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Pembentukan sel memori & Ab
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SELULER – Sel T
Tujuan: Menghancurkan Ag intraseluler Sel yang berperan:
Antigen Presenting Cel/APC (Makrofag) Sel T {sitotoksik (Tc), supresi (Ts), helper
(Th) } Sel NK
Pengenalan sel terinfeksi MHC
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Reaksi Seluler Imunitas DAPATAN
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Major Histocompatibility Complex (MHC)
Berdasarkan struktur, fungsi dan distribusi di jaringan, Jenis: - MHC I & MHC II
Pada manusia dikenal dengan HLA
MHC I glikoprotein integral membran fungsi: reseptor antigen yang telah
diproses
dan melibatkan reaksi selular
letak gen: manusia → lengan pendek krom. 6
tikus → lengan pendek krom. 17
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-Tikus = H-2k, H-D dan H-L
- Manusia = HLA-A, HLA-B, HLA-C- terdapat pada sel tubuh
MHC II Terdapat pada: sel B, makrofag, sel dendritik, sel
Langerhans Tikus: I-A dan I-E Manusia: HLA-DR, HLA-DQ, HLA-DP, HLA-DO, HLA-
DZ Glikoprotein
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STRUKTUR MHC
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Skema Prossesing & Presenting Ag
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Sel efektor Kekebalan DAPATAN
Limfosit T
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Skema Respon Imun
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DEFINISI
Adalah : memberikan kekebalan
Individu yang belum mengenal Ag & dipaparkan dengan Ag akan melakukan RESPON PRIMER
Bila dipaparkan kembali dengan Ag yang sama menghasilkan RESPON SEKUNDER
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Respon PRIMER & Respon SEKUNDER
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Respon Primer Respon Sekunder
- lambat - cepat
- mudah hilang - tahan lama
- kadar/intensitas - tinggi
rendah
- spesifisitas rendah - tinggi
- IgM > IgG - IgM < IgG
- umumnya - tidak sakit
mengalami sakit
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Imunisasi ada 2 macam:
1. Kekebalan alami:- kekebalan alami pasif : maternal misal: ASI
- kekebalan alami aktif : pernah sakit & tinggal di daerah endemis2. Kekebalan buatan: - kekebalan buatan pasif : Ab misal: ABU (anti bisa ular), ATS - kekebalan buatan aktif : Ag
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- mikroorganisme utuh yang dilemahkan
- mikroorganisme utuh yang dimatikan
- Komponen mikroorganisme, misal:
- membran sel
- flagel
- toksin yang dilemahkan atau komponennya
- gen
Ag yang digunakan pada kekebalan buatan aktif
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1. Usia, tidak dapat digeneralisasi2. Gender, laki-laki atau perempuan3. Dosis & interval,4. Cara pemberian, oral, IM, SC, IP, IC5. Lokasi anatomik,
Misal: Pemberian secara IM ditentukan
dimana?
Faktor-faktor yang mempengaruhi keberhasilan imunisasi
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Bahaya Imunisasi
1. Hipersensitifitas, misal virus influenza, banyak yang
alergi terhadap komponen penyertanya, a.l: Telur ayam
2. Imunokompremasi, bila menggunakan vaksin
hidup yang dilemahkan, karena diduga dapat
bermutasi menjadi virulen3. ibu hamil dan akan hamil, misal MMR karena
dapat memberikan gangguan pada bayi
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KONSEKUENSI KLINIK
Imunitas terhadap mikroorganisme Infeksi (bakteri, virus, parasit, jamur)
Imunodefisiensi AIDS → menyerang sel Thelper
SLE → HLA-DR2 dan HLA-DR3 Alergi → reaksi hipersensitivitas (IgE) DM tipe I → HLA-DR3 dan/atau HLA-DR4 Neisseria meningitidis dan Neisseria
gonorhoeae → C6-C9 Transplantasi → MHC
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Jangan lupa…..
dibaca lagi.. OK !…