Neonatal Immunity.pdf

IMMUNE SYSTEM ONTOGENY AND NEONATAL IMMUNOLOGY Noman Naseem VETS2007 [email protected] Learning objective Understand the development of the immune system in utero Understand species differences in maternal transfer of immunity Describe the routes of maternal transfer of immunity and the effects...

IMMUNE SYSTEM ONTOGENY AND NEONATAL IMMUNOLOGY Noman Naseem VETS2007 [email protected] Learning objective Understand the development of the immune system in utero Understand species differences in maternal transfer of immunity Describe the routes of maternal transfer of immunity and the effects of its failure Understand how neonatal immunity is measured Lymphoid organs Primary = where lymphocyte development takes place Secondary = where mature lymphocytes migrate for antigen presentation Development of the immune system Development of lymphoid organs/lymphoid cells B cells (but Abs appearing later) • Pregnancy = 15 days • No immunological tissues or organs at birth • Abs production 7 days pp Foetuses are able to respond to antigens, but immune competence is attained after birth (neonates do not have a fully protective immune system!) Development of the immune system Few examples Gestation: 340 days 60 80 90 120 175 240 340 Development of the immune system STEM CELLS Incubation time = 21 days Lymphoid follicles VACCINATION OF EMBRYONATED EGGS IgMpositive B cells 5 7 12 14 16 IgY-positive B cells 21 IgApositive B cells 1 wk after hatching Development of the immune system Immunity is not fully developed until 12 months of age + at birth they are moving from a completely sterile environment to a non-sterile environment PROBLEM #1: The neonatal immune system is not fully protective at birth– not able to synthesize their own antibodies PROBLEM #2: Neonate is vulnerable to infection due to immune immaturity How are these problems overcome? MATERNAL TRANSFER OF IMMUNITY • Transfer of antibodies from the mother to the foetus/neonate (Maternal antibodies, MAB) • Transfer may be either prenatal or postnatal • The time frame of MAB transfer determined by the type of placentation (varies between species) MATERNAL TRANSFER OF IMMUNITY PRENATAL TRANSFER Placental structure affecting the prenatal transfer of Igs MATERNAL TRANSFER OF IMMUNITY What type of placenta in primates and rodents? Haemochorial placenta IgG Much maternal transfer before birth (but IgA and IgG are transferred after birth as well) MATERNAL TRANSFER OF IMMUNITY What type of placenta in horses, cattle, pigs? Epitheliochorial placenta IgG All maternal transfer after birth MATERNAL TRANSFER OF IMMUNITY What type of placenta in cats and dogs? Endotheliochorial placenta • IgG (but less than in primates) • 5% or less of the level of serum Igs in pups and kittens Maternal transfer continuing after birth MATERNAL TRANSFER OF IMMUNITY Passive immunity in the chick Active transport of serum Igs from the hen’s serum to the yolk In chick at hatching: IgY in the serum, IgA and IgM in the intestine (maternal Abs persisting from 14-21 days) In chick embryos • IgY from the yolk to the serum • IgM and IgA from the albumen to the amniotic fluid and then the intestine MATERNAL TRANSFER OF IMMUNITY POSTNATAL TRANSFER OF IMMUNITY • Colostrum = secretions of mammary gland over the last few wks of pregnancy and proteins transferred from the blood (IgG = 6590%) • As the lactation progresses and colostrum changes to milk • Cytokines (IL1, Il6, TNF, IFN) Lymphocytes, mainly T cells producing IFNγ (> early development of Th1 response); few or no lymphocytes in the milk MATERNAL TRANSFER OF IMMUNITY Absorption of colostral Igs (must take place within 18-24 hrs after birth) IgG, IgM IgA FcRn receptors on enterocytes No digestion ingested antibodies • Low protease levels • High trypsin inhibitors in colostrum Transient proteinuria Some loss via neonatal glomeruli (permeable 24 hrs) Lacteals and blood capillaries Circulation (peak serum in 12-24 hrs) Gut permeability reaching zero > maternal transfer through milk with more IgA > protection against enteric pathogens MATERNAL TRANSFER OF IMMUNITY Failure of passive transfer Premature birth the dam has not formed colostrum Premature lactation Understand species loss of colostrum Poor-quality Poor nutrition of the dam during the dry period, reduce dry period, stress Ingestion failure Multiple births, Poor mothering, Weak newborn, Poor suckling, Physical problems Failure to absorb especially in horses because, about 25% of newborn foals fail to absorb sufficient immunoglobulin NEONATAL VACCINATION Maternal antibodies are useful, but they are an obstacle to vaccination! Why? • Block of essential BCR epitopes (no endogenous humoral immune response) • Binding to injected antigens before activation of a new immune response Window of susceptibility = period when there is no longer sufficient maternal Ab to afford protection from infections, but there is still enough maternal Igs to prevent the newborn from mounting its own protective immune response to a vaccine NEONATAL VACCINATION PUPPY A Serum Igs Maternallyderived Ig 8 Serum Igs Inter-animal variation in the “window of susceptibility” Endogenous Ig 10 12 14 16 PUPPY B Example: 2 puppies from the same litter but taking a different amount of colostrum. What is the window? PUPPY A: > colostrum; window between 10 and 12 wks PUPPY B: less colostrum; window between 8 and 10 wks What happens if receiving only a single vaccination at 10 wks? Endogenous Ig Maternallyderived Ig 8 10 12 14 16 Puppy A would not respond NEONATAL VACCINATION Inability to define and quantify the window in individual newborns > vaccination protocol with multiple vaccinations 6-8 wks 10-12 wks 14-16 wks 1 yr after EARLY LIFE IMMUNE DEVELOPMENT In most species, immunity is not fully developed until 12 mo of age • Increased number of blood lymphocytes in the first few months; CD4:CD8 ratio gradually decreasing (increased CD8) • Adult levels of endogenous IgG, IgM and IgA achieved in up to 12 months • Thymic involution starting at 6 months