html5-img
1 / 26

Transfer of Immunity

Transfer of Immunity. D. I. Stott. Introduction. Fetus as allograft . Rejection avoided by:- Separation of fetal & maternal circulation No MHC Class I & II on trophoblast Placental hormones (progesterone, prostaglandin) & cytokines (IL-4, IL-10) suppress Th1 (but not Th2) response

fritz
Télécharger la présentation

Transfer of Immunity

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Transfer of Immunity D. I. Stott

  2. Introduction • Fetus as allograft. Rejection avoided by:- • Separation of fetal & maternal circulation • No MHC Class I & II on trophoblast • Placental hormones (progesterone, prostaglandin) & cytokines (IL-4, IL-10) suppress Th1 (but not Th2) response B. Newborn very susceptible to infection Immature defences:- • Barrier function (skin & mucosal surfaces) • Innate I.S. • Specific adaptive I.S. (no memory)

  3. Protection provided by mother:- • Prenatal (placenta or yolk sac) • Postnatal (colostrum & milk) Route & mechanism of transport differ between species.

  4. Route of Transmission of Abs. from Mother to Infant’s Blood

  5. Prenatal Transfer of Immunity Evidence:- Rodents & rabbits • ligation of yolk sac prevents tf. of Abs Man & primates • Gm allotype on maternal Ab  fetus via placenta

  6. Transfer of IgG from mother to fetus is via FcRn Evidence:- • Expressed on yolk sac & gut epithelium (rodents) and trophoblast (man) • FcRn K.O. mice – no transfer of Ig to fetus (yolk sac) or neonate (colostrum)

  7. Properties of FcRn • Homology with MHC Class I •  chain + 2--globulin • Binds IgG at pH 6.0 • Released at pH 7.4 • X-ray Xlly suggests 2 FcRns bind 1 IgG

  8. Structure of FcRn

  9. Mechanism of Transfer (1) Rodent yolk sac & Human Placenta • Neutral pH both sides,  uptake of fluid-phase IgG by pinocytosis • Endosome  acidic • IgG binds FcRn & transcytosis • Release into blood (pH 7.4) From Rojas & Apodaca (2002)

  10. Mechanism of Transfer (2) • In rodent gut lumen, acidic pH, IgG binds FcRn on apical surface of gut epithelial cell. • Pinocytosis & transcytosis • Release into blood (pH 7.4)

  11. Immunoglobulin Levels in Prenatal & Newborn Infants IgG levels of newborn infants are low from c.3 – 6 months after birth

  12. FcRn also regulates serum IgG level in adult Evidence:- • FcRn expressed on vascular endothelial cells. • FcRn K.O. mice: IgG has faster turnover • SDM of IgG Fc to lower K for FcRn  lowerserum IgG level • SDM of IgG Fc to higher K. for FcRn  slower turnover and higher serum IgG level • Implications for Ab therapy?

  13. Homœostasis of IgG in Blood • High plasma concn.: unbound IgG degraded in endosomes of endothelial cells • Low concn. FcRn- bound IgG protected & recycled

  14. Maternal Abs can be harmful1. Autoimmunity • Mother with autoimmune disease • IgG autoantibodies transported across placenta • Baby born with symptoms of mother’s autoimmune disease • Resolve when maternal IgG degraded

  15. Maternal Abs can be harmful: Graves’ Disease • Mother produces IgG anti-TSHR Abs • Anti-TSHR Abs cross placenta to fetus • Stimulate fetal thyroid gland • Baby born with same symptoms as mother

  16. Maternal Abs can be harmful: Neonatal Lupus Erythematosus Cutaneous NLE Annular erythematous plaques on the head of an infant. All manifestations of NLE eventually resolved. Lee, L.A. (2005) Autoimmunity Revs. 4, 207 – 213.

  17. Maternal Abs can be harmful: Haemolytic Disease of Newborn (HDNB) • Rh- mother & Rh+ father  Rh+/- fetus • 1st birth = Sensitisation  IgG anti-RhD • 2nd pregnancy: IgG anti-RhD crosses placenta • Ab-coated fetal RBC phagocytosed in liver  HDNB • Prophylaxis: Anti-RhD i.v. immediately after delivery.

  18. Haemolytic Disease of the Newborn

  19. A Baby with HDNB

  20. Reduction in Child Mortality due to Anti-RhD Prophylaxis

  21. Postnatal Transfer of Immunity from Colostrum and Milk • Rodents & Ungulates: IgG uptake across gut epithelium via FcRn. • Man: Very little or no IgG uptake; • IgA stays in gut, protects mucosal surface. Also synthesised locally.

  22. Ig Concns. in Human Colostrum & Milk

  23. Antibodies in Human Milk • P.C.s & activated B & T-L.s from Peyer’s patches migrate to mammary gland • Also activated. L.s from systemic I.S.  broad range of Abs. • Abs v. many bact. & viral ags. in milk • IgA transport via polyIg rec. (secretory piece), as into gut

  24. Other Components of Human Colostrum & Milk • Complex oligosaccharides – inhibit adherence of bact. to cells • Lactoferrin – binds Fe • Lysozyme – degrades bact. cell wall

  25. Protective Effects of Breast v. Bottle Feeding *Risk ratio =  of disease bottle fed/  breast fed

  26. Human Breast Milk Substitutes

More Related