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Reproductive Immunology

Explore comprehensive screening methods and significance of sperm antibodies, zona pellucida antibodies, and antiphospholipid antibodies in infertility cases. Learn about detection techniques, historical background, and immunological origins in men and women.

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Reproductive Immunology

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  1. ReproductiveImmunology Prof. MUDr. Zdenka Ulcova-Gallova, DrSc. Genetics –Pilsen and Department ofGynecology and Obstetricsof Charles University, Pilsen, Czech Republic www.ulcovagallova.cz Ulcova-Gallova@email.cz

  2. Neuro-hormonal-immu- influences

  3. Screeningforreproductiveimmunology (RI) • Spermantibodies • Zonapellucidaantibodies • Panel of variousantiphospholipidantibodies (eight) • Embryocytotoxiccytokines • Intraacrosomalproteins • Endometrial Ab • Antitrophoblastantibodies • aTSH, aTPO • HLA-I a HLA II • HLA-G • AMH • Inhibin (A, B) • Local CD56+/CD16+ • Detailedimmunological profile according to basic dg.(CD56/CD16)

  4. RI Men Women Both

  5. Immunologicalorigin in unknown/known cause of infertility • Repeatedspontaneousabortionormissedabortion • Repeated IVF failure • Patientswithautoimmuneoroncologicaldiseases • Endometriosis, preeclampsia, PCO, POF, HELLP….. • Andrologicalfactor

  6. Zonapellucidaantibodies Spermantibodies

  7. Anti-spermantibodies (ASA) • History • Incidence in men, women • Methodsofmeasurement • „Treatment“

  8. Richhistoryof ASA • Animals: 1899 by Landsteiner and MetchnikoffMetalnikoff 1932 Baskin Humanstudies:Rumke 1954, Bronson, Shulman (1991), Dondero, Hendry, Fjallbrandt, Hjort, Isojima, Mori, Koyama,Kutteh, Moghissi, Nakov, Bratanov, Lenzi, Mathur, Ingerslev, Clark,Mettler, Ulcova-Gallova (1985), Bohring, etc. Multicentric study -1994-2010, comparisonofvarioustestsfordetectionof ASA

  9. Originof ASA in men • Damageofbloodtestis-barrier • Geneticpredisposition HLA A-28, B-22

  10. Originof ASA in women • Ascendent immunisation (but otherwayispossible)

  11. Sperm antibodies inhibit from: • Sperm transport • Bloking ZP penetration • Sperm capacitation • Acrosomal reaction • Early fertilization • Postfertilization effect

  12. Examination • Serum • Semen • OCM • Peritoneal fluid • Folicular fluid

  13. Detectionof free ASA • Gelatinagglutinationtests (GAT-Kibrick) • Tube-SlideAgglutination test • Trayagglutination test (TAT-Friberg) • Sperm-immobilization test(Isojima) • Mixedreaction anti-immunoglobulintests (MAR-test) • Immunobeadtechnique • ELISA (poorcorrelationwith infertility) • RIA

  14. ASA • IgG • IgM • IgA, s IgA • (i IgE)

  15. ASA and significance • Sperm-agglutinating • Sperm-immobilising • Sperm-cytotoxic

  16. Prof. Isojima S. • Publication • Science • AJRI, 1988-2004

  17. Kibrick test Shulman,1985

  18. Capillary test (Fjallebrandt) Shulman,1985

  19. Sperm-agglutination head to head -TAT

  20. Methods • Direct i i-MAR-test (indirectmixedantiimmunoglobulinreaction test forIgG, IgA ( IgM, IgE) /orimmunobead test 49% Ig H-H

  21. OCM • The Miller-Kurzrok Test) • TheSpermCervicalMucusContact Test • Kremer test

  22. Kremertest

  23. Antizonal antibodies (aZP) • Block sperm adherention and sperm penetration into oocyte • Postfertilization effect

  24. Zonapellucida • Animal models (Oikawa, Yanagimachi, Kamada, Mori, Aitken, Hasegawa, Koyama, Isojima, Inoue, Yamasaki, Clark, et al.) • Importanceof ZP • ZP epitopes

  25. ZP • Human ZP X porcine ZP (Sacco, 1977)

  26. AJRI • Ulcova-Gallova Z., Mardesic T.: Does In Vitro Fertilization ( IVF ) Influence theLevelsofSperm and ZonaPellucida ( ZP ) Antibodies in InfertileWomen? Amer. J. Reprod. Immunol. 1996, 36, p.216-219 • Very important!!!

  27. ZP antigens • Porcineoocytes ZP1 –ZP4 epitopes (60 kDa, Hasegawa et al. 1995) Mice –ZP 1- ZP3 Monoclonalantibodies

  28. Koyama, Hasegawa, Mochida, Colongos, 2005-2015 • Inductionoffolliculardysfunction by ZP • E.g. ↑aZP in POF • Et al.

  29. ExaminationofaZPantibodies • Passive haemmagglutination tests • ELISA

  30. Antiphospholipid antibodies Interference with membrane phospholipid 1. Prae-conceptionally 2 .Post-conceptionally

  31. APA (IgG, IgA, IgM) • Ph-L-serine • ph-L-glycerol • ph-L-inositol • ph-ethanolamine -annexin V • ph-acid • cardiolipin • b2-GP

  32. Criteriaof APA sy • -primary • -secondary(withautoimmunedisease) In general: • aPls • Thrombosis (thrombocytopenie?) • Failure in reproduction

  33. For instance • Immuno-histologicaldetection a-annexin V Ab

  34. Červeně: apoptotic.buňky Zeleně: mrtvé buňky

  35. Detectionofintracrosomalenzymes • IF (monoclonalantibodies)

  36. Immunological tolerance • Mother X foetus

  37. Dr. Peter Medawar a prof.MilanHasek

  38. Nidation and implantation

  39. Mother -immunotolerance • Barier of decidua • Blockadeantibodies • Immunotolerance to foetusantigens • Pregnancyspecificproteins (Bohn p.) • HCG, E, P • Anti-idiotypeantibodies • Immunosuppressivecells (spec., non-sp.) • Othermechan.

  40. Foetus -immunotolerance • Throphoblastbariereof placenta • Sialomucinglycocalixlayer • Lowexpressionof MHC • Damping elements:e.g. α FP, PGE, … • C system

  41. Ab -detection • Anti-foetus • Anti-placental • Anti-paternal

  42. Development of a particular immune response which enhances embryo acceptance Recognition by decidual cells Th2 Trophoblast antigens HLA-G? CD46? R80k? CD1? γδTcells? Th2 RESPONSE Th2 • Immunoabsorbent placenta • Trophoblast resistant • to NK cell lysis • Local hormone-dependent immunosuppression FACILITATION REACTION IMMUNOTROPHISM growth, maturation of the placenta Blocking antibodies  BLOCKAGE of cytotoxic reactions ? ΑΝΤΙΓΟΝΑ ΤΡΟΦΟΒΛΑΣΤΗΣ HLA-G; CD46; R80k; CD1; ; «ÔÇ2»

  43. Rh-incompatibility(ery-C,D,E,c,d,e) • Rh negative mother • Rh positive foetus • Treatment: anti D (to 72 hours) • ABO –incomp.veryrare • Keely, Lewinetc.

  44. CAVE! • - foetuserytroblastosis • 1. Anaemianeonatorum • 2. Icterusneonati gravis • 3. Hydrops fetus universalis

  45. 15-20% ofinfertilecouple • Clearimmunological cause of infertility orcombinewithothercauses

  46. FERTILITY and RI • biologicagingofthehypothalamic-pituitary-ovarian axis in elderwomen • →changes in endocrinology, immunity, psychology • Tests in RI withereason

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