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FAKTOR IMUN & FERTILITAS

FAKTOR IMUN & FERTILITAS. Imunologi: gamet dan embrio implantasi. Antisperm antibodies (ASA) terjadi: pria dan wanita Pria: penyakit autoimun  infertilitas Karaterisasi protein spermatozoa dgn antigen  antibodi Fungsi spermatozoa - fertilisasi ↓ : cervix mucus penetration,

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FAKTOR IMUN & FERTILITAS

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  1. FAKTOR IMUN & FERTILITAS

  2. Imunologi: gamet dan embrio implantasi • Antisperm antibodies (ASA) terjadi: pria dan wanita • Pria: penyakit autoimun  infertilitas • Karaterisasi protein spermatozoa dgn antigen  antibodi • Fungsi spermatozoa - fertilisasi ↓ : • cervix mucus penetration, • zona binding, • zona penetration, • oolemma binding, and • pronucleus formation

  3. Immunology of male infertility ASA can be defined as immunoglobulines of the IgG, IgA and/or IgMisotype that is directed to various aspects of the spermatozoa (head, tail, midpiece or combination thereof). Immunoglobulin M is too large molecule to cross into the semen. Immunologic infertility is probable if more than 50% sperm are bound to IgG or IgA antibodies. It may be suspected if more than 10% spermatozoa are antibody bound. These immunoglobulines can be found in both males and females and in serum, semen and cervical mucus.

  4. The blood-testis barrier, the tight junctions between Sertoli cells appears to play a major role in keeping the developing spermatozoa and immune system separate. It prevents those testicular cells expressing "foreign" antigens from coming into contact with lymphoid tissue and immunocompetent cells from entering the seminiferous tubules. However, the BTB is commonly breached by physiological leakage of normally sequestered sperm antigens. Since tight junction does not protect all intratesticular sperm autoantigen due to the presence of autoantigenic cells (spermatogonia and early spermatocytes) below the junction in the basal compartment, other immunosuppressive

  5. Immunology- fertilization • Untukmenentukankualitasfungsi spermatozoa dalamfertilisasi ujiimunnitas (immunobead test) • Abmengikat Ag spesifik (lock-and-key)  AgAbkompleks • Ab  molekul protein = imunoglubulin • Imunoglubulin: IgG, IgA, IgD, IgE, danIgM. • IgA, IgG  motilitas • Abdikepala spermatozoa  fertilisasi • Alami  Ag adadi seminal plasma dinetralisirolehAbdi seminal (ASA)  fungsi spermatozoa

  6. Maturasi Spermatozoa • Spermatozoa  testis: • immotil, • nor-fertil • Kemampuan tinggi  menuju epididimis

  7. Sperm Maturation

  8. Spermatozoa mulai aktif  dalam epididimis • Aktivator  di epididimis • Produk ratusan juta spermatozoa  ejakulat • Kontrasepsi  hormonal (cepat dan reversible)

  9. Fertilisasi  tidak hanya ditentukan oleh jumlah spermatozoa yang ada di saluran repro jantan, tetapi juga yang ada di saluran repro betina • Kondisi lingkungan mikro yang berbeda  meningkatkan perkembangan kemampuan segregasi protein membran spermatozoa menjadi adaptif terhadap lingkungan baru untuk fusi dengan ZP • Spermatozoa yang tidak mengalami segregasi protein membrannya  protein tidak dikenali oleh ZP (protein mistarget)  infertil

  10. Penyebab infertilitas • Wanita • Faktor fisiologi (81%) • Faktor psikologis (19%): Ketidak seimbangan jiwa dan kecemasan berlebihan (stres) • Pria

  11. Masalah Wanita: • Anatomo fisiologi vagina, servik, uterus, ovarium, dan peritonium • Masalah pria: • Kualitas spermatozoa (koagulasi, viskositas, rupa & bau, volume, pH, kadar fruktosa dalam semen, dan sistem imun

  12. Faktor imun penyebab infertilitas • Peran: • sel T & B serta • makrofag • Imunoglobulin: • IgA: serum danmukus vagina/servik • IgG: mudahberdifusidlmekstravaskuler • IgM: besar, terletakdiintravaskuler • IgE: serum, cairansekresi • IgD: serum, dipermukaansel B

  13. Deteksi Ab pada pasutri • Langsung: • Ab yang terikat langsung pada spermatozoa • Tidak langsung: • Kadar Ab di serum, semen, sekresi vagina, sekresi servik

  14. Macam metode deteksi Ab • UjiKibrick • UjiIsojima • Uji Kremer & Jager • Imunobead assays (IBD) • Mixidantiglobulin reaction (MAR) test • ELISA • Tray aglutination test (TAT) • Sperm immobilisation assays test, flow cytometry • Radiolabeledagglutininassays

  15. Langkah Pemeriksaan Tes imobilisasi spermatozoa Tes kontak spermatozoa-mukus servik, diukur kadar Ab Tes aglutinasi Ab lokal (SIgA): ASA Tes dengan mikroskop immunofloresen (tidak rutin)

  16. Pengobatan 1. Turunkan produksi ASA 2. Hilangkan ASA yang terikat pada spermatozoa 3. ART (assisted reproductive technology) Ke3 strategi tsb scr teoritis dapat menurunkan paparan gamet oleh ASA, shg fungsi gamet meningkat

  17. Macam terapi Inseminasi dengan spermatozoa donor (?) Terapi imunosupresif Manipulasi spermatozoa

  18. Expression of ASA during in sperm maturation detected with monoclonal antibodies B C A D E

  19. TERIMA KASIH

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