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Male Immunological In ferti lity

Male Immunological In ferti lity. 田美策 孙钦辉. 魏源 魏艳 王思宇. Sir Frank Macferlane Burnet Clonal Selection Theory. Clonal Selection Theory. There are various lymphocyte clone,each of them bears a single type of Ag receptor of unique specificity.

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Male Immunological In ferti lity

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  1. Male Immunological Infertility • 田美策 孙钦辉 • 魏源 魏艳 王思宇

  2. Sir Frank Macferlane Burnet Clonal Selection Theory

  3. Clonal Selection Theory • There are various lymphocyte clone,each of them bears a single type of Ag receptor of unique specificity. • Ag receptor—Ag’s specific interactions lead to lymphocytes activation (proliferated ), then produce both Ab and memory cells.--- Clone selection • Those clones whose receptor can recognize self will be destroyed or learn to tolerance to self Ags (forbidden clones) at early stage.—Clone deletion • forbidden clones can be revival and cause antoimmunity

  4. For male, spermatogenesis commences(发生) well after the development of neonatal (new born) immune tolerance • And for female, sperm is definitively “non-self”

  5. Mechanisms normally in place to modify the immune response and prevent immune reaction • Blood-testis barrier • Sperm plasma immunosuppressive factors(精浆免疫抑制因子)

  6. The barriers may be disrupted, result in the exposure of sperms to the immune system. • And thus the production of antibody

  7. research on sperm as an antigen has been making little progress

  8. So what do we know about sperm asan antigen? Spermatogenic cells Mostly Membrane proteins Sustentacular cells Deputy gonadal components (副性腺成分)

  9. Mechanism of anti-sperm antibody causing infertility Direct binding influence Function impairment of antigen molecules

  10. Direct binding influence 1.Occlude the sperm penetration through the cervical mucus 2.Accelerate the clearance of sperms in the female genital canal (mainly carried out by complements)

  11. Antigen function impairment • Inhibit fertilization

  12. AsAb binds to Ag P36 and P18, manifesting a reduction of penetration through zona pellucida and oval membrane. Induced spontaneous acrosome(顶体) activation and acrosomal enzyme lost

  13. Failure of fertilization………

  14. Diagnostic techniques Traditional methods sperm membrane extract(膜提取物) or motile sperms(活动精子) as antigen to detect AsAb Being questioned for deficiency and uncertainty

  15. Diagnostic techniques According to WHO Diagnostic basis the surface of motile sperm is attached by immunoglobulin positive result of IBT or MAR

  16. IBT----immunobead test(免疫珠试验) • Utilize polyacrylamide beads(聚丙酰烯胺珠) coated with Ig to human IgG, M and A to detect AsAb.

  17. MAR----mixed agglutination reaction(混合凝集试验) • Uses anti-human Ig to mediate agglutination between latex(胶乳) beads or SRBC labeled with human Ig and viable sperms (活性精子)

  18. Standard ofIBTandMAR • The percentage of viable sperms attached by AsAb among all viable sperms • Detect not only the existence of Ig, but also the position of attachment

  19. Clinical therapy • Different percentage and site of attachment have different clinical significance • It is recommended to choose different methods according to the percentage of sperms attached by AsAb, particularly to their heads.

  20. Clinical therapy • From the lowest highest • We choose IUI IVF ICSI

  21. IUI----intrauterine insemination Send sperms directly into the uterine cavity First choice for male immunological infertility

  22. IUI----intrauterine insemination

  23. IVF---- in vitro fertilization • Not only overcomes the difficulty of AsAb-attached sperms penetrating the cervical mucus, but also make sure there are enough sperms contacting with ovum.

  24. IVF---- in vitro fertilization

  25. ICSI----intracytoplasmic sperm injection • The most effective method for severe immunological infertility • But with the highest cost tens of thousands of dollars!

  26. Other options • Isolation therapy (using condom) • Immune inhabitation (large-dose-glucocorticoid injection) …….

  27. There are questions remaining to be answered!!!

  28. Acknowledgements • Sperm antigen----------------------魏艳 • Production of AsAb----------------魏源 • Mechanism of infertility-----------田美策 • Diagnostic techniques------------孙钦辉 • Clinical therapy---------------------王思宇

  29. Thanks all !

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