Fetal and Neonatal Immunity PDF

Fetal and Neonatal Immunity Dr Felix N. Toka, DVM, PhD, DSc., DACVM Professor, Veterinary Virology Department of Biomedical Sciences Objectives In general terms, describe the fetal development of immune competence in animals Briefly describe immune response of newborn...

Fetal and Neonatal Immunity Dr Felix N. Toka, DVM, PhD, DSc., DACVM Professor, Veterinary Virology Department of Biomedical Sciences Objectives In general terms, describe the fetal development of immune competence in animals Briefly describe immune response of newborn mammals Describe species differences in maternal transfer of immunity and the underlying causes of these differences Explain the rationale for neonatal vaccination  At birth animals move from a sterile environment to one with many pathogens to survive they should be able to control infection the innate immune mechanisms are functional but adaptive mechanisms, although present (in certain species), are not fully functional the newborn relies on passive immune transfer from the mother Development of the Immune System the thymus develops first secondary lymphoid organs are second B cells appear soon after the spleen and lymph nodes have developed antibodies are not usually found until late in fetal life, if at all  Calf gestation period of the cow is 280 days. Fetal calves can respond to rotavirus at 73 days, to parvovirus at 93 days, and to parainfluenza 3 virus at 120 days. Puppy the gestation period of the bitch is about 60 days. the thymus differentiates between days 23 and 33 thymic seeding with T cells is quite late The Immune System and Intrauterine Infection mild or unapparent infections in the mother may be severe or lethal in the fetus the response to infection is determined by the state of immunological development of the fetus  Effects of the timing of viral infection are well seen with bovine viral diarrhea virus (BVDV) Pregnant cows infected with a non-cytopathic BVDV early in conception up to 120 days will give birth calves that are tolerant to BVDV Cows infected with a non-cytopathic BVDV between 120 and 200 days will give birth to normal calves Infection of pregnant cows with a cytopathic BVDV within the first 100 days of conception will lead to abortion, resorption or mummification of the fetus  Malformations may occur in calves originating from mothers infected with cytopathic BVDV between 100-150 days from conception Calves from mothers infected with cytopathic BVDV after 150 days from conception may be born normal Immune Response of Newborn Mammals young mammals are capable of mounting both innate and adaptive immune responses at birth any adaptive immune responses are primary responses innate immune responses are therefore critical in newborn animals Innate Immunity Newborns can produce antimicrobial molecules, such as lectins, pentraxins, collectins, defensins, lactoferrin and lysozyme. Serum amyloid A (SAA), lipopolysaccharide-binding protein, haptoglobin and α1-acid glycoprotein are present in high concentrations immediately after birth but gradually decline by 21 days serum of the newborn mammals are deficient in some complement components, resulting in a poor opsonic activity C3 in newborn piglets reaches adult levels by 14 days of age  macrophages are capable of phagocytosing bacteria such as Staphylococcus aureus, but less efficient at killing, until after 7-10 days newborn calves have fewer NK cells which respond more strongly to IL-2 or IL-15 and are more cytotoxic Adaptive Immunity most newborn mammals, mount adaptive responses skewed toward Th2 rather than Th1 cells the reason for this is the delayed development of IL-12-producing DC1 cells in presence of activity of DC2 cells that produce IL-4 and IL-13 neonatal Th1 cells are slow to develop  In the first 3 months, dog puppies have a higher lymphocyte count than adult dogs. this is due to more CD21+ B cells than CD8+ T cells (similar in kittens) thymic involution begins at around 6 months of age in both dogs and cats. Transfer of Immunity from Mother to Offspring Transfer of maternal antibodies to the fetus depends on the structure of the placenta Hemochorial placenta (primates) - allows transfer of maternal IgG but not IgM, IgA, or IgE In those animal species in which antibodies cannot be transferred to the newborns through the placenta, newborns are entirely dependent on antibodies received through the colostrum This is referred to as transfer of passive immunity Secretion and Composition of Colostrum and Milk What is colostrum? Accumulation, in the mammary gland, of the last few weeks of gestation  all IgG, most of IgM, and half of IgA in bovine colostrum are derived from the bloodstream 30% of IgG and 10% of IgA in milk are produced locally within the udder colostrum is rich in cytokines bovine colostrum contains significant amounts of IL-1β, IL-6, TNF-α, and IFN-γ Absorption of Colostrum newborn mammals ingest colostrum (2-6 L) but do not digest it in newborn mammals, protease activity in the digestive tract is low trypsin inhibitors in colostrum reduced protease activity colostral proteins are not degraded but can reach the small intestine intact  duration of intestinal permeability is highest immediately after birth and declines after about 6 hours absorption of all immunoglobulin classes drop to a very low level after about 24 hours Failure of Passive Transfer When a new-born cannot uptake the appropriate amount of colostrum, it is referred to as “failure of passive transfer” three major reasons for failure of passive transfer: production failure - the mother may produce insufficient or poor- quality colostrum (refer to the table on slide ) ingestion failure - sufficient colostrum production but inadequate intake by the newborn animal absorption failure - failure to absorb in the intestine despite an adequate intake of colostrum Production Failure premature births may mean that insufficient colostrum has accumulated premature lactation or excessive dripping before birth reduce the amount and quality of colostrum good quality colostrum has specific gravity of 1.060 to 1.085 (measured with a colostrometer), equivalent to an IgG concentration of 3000 to 8500 mg/dL below 3000 mg/dL – poor quality colostrum, which may not protect the newborn Ingestion Failure multiple births mean less colostrum for all litter mates - inadequate intake poor mothering, an important problem among young, inexperienced mothers physical problems such as damaged teats weakness in the newborn, a poor suckling drive, or jaw defects Diagnosis of Failure of Passive Transfer Usually measured after 18-24 hours when most absorption of antibodies is complete Vaccination of neonates Maternal antibodies that protect the neonates can interfere with vaccination Maternal antibodies can bind vaccines antigens and prevent generation of an immune response Antibody-antigen complexes formed this way are cleared by cells that posses Fc receptors e.g., erythrocytes Maternal antibodies can mask the antigenic epitopes thus preventing B cell responses Vaccinate after the level of maternal antibodies has declined