13 Immunity in the Fetus and Newborn

1. 13Immunity in the Fetus and Newborn

2. 13-1 Development of the Immune System • The thymus is the first immune organ to develop. • The development of secondary immune organs. • B cells appear soon after the development of the spleen and lymph node, but antibodies are not usually found until late in fetal life.

3. The ability of the fetus to respond to antigens develops very rapidly after the immune organs appear, but all antigens are not equally capable of stimulating fetal response. • The ability to mount cell-mediated immune responses develops almost simultaneously as antibody production.

4. Calf • The gestation period of the cow is 280d. • The fetal thymus is recognizable by 40d postconception. • The bone marrow and spleen appear at 55d. B cells work? • Lymph nodes are found at 60d, but Peyer’s patches don’t appear until 175d.

6. Lamb • The gestation period of the ewe is about 145d. • MHC class I positive cells can be detected by 19d after sex service. • MHC class II positive cells can be found by 25d. • The thymus and lymph nodes are recognizable by 35d and 50d, respectively. CD4+ and CD8+ cells appear in the thymus by 35 to 38d.

7. Lamb • Blood lymphocytes are seen by 32d. • B cells are detectable at 48d in the spleen. • The Peyer’s patches appear only at 60d. • C3 receptors appear by 120d, but Fc receptors don’t appear until the animal is born.

8. Piglet • The gestation period of the sow is about 115d. • The first leukocyte can be found in the yolk sac and liver at 17d. • The thymus develops by 40d postconception. • The intestinal lymphoid tissues are devoid of T cells at birth. • CD4+T cell appear in the intestine at two weeks of age and CD8+T cells at 4 weeks.

9. IgM+B cells can be found in blood by day 50 during the conception. • NK cells don’t develop until several weeks after birth. • B cells can be found in the thymus of newborn piglets!!! • The VDJ rearrangement is first seen in the fetal liver at 30d. • IgM, IgA, and IgG transcripts are present at 50d.

10. Chick • 21-day of hatching eggs. • Stem cells arise in the yolk sac membrane and migrate to the thymus and bursa at 5 to 7 days of incubation. • IgM+ lymphocytes are detected in the bursa by day 14. Antibodies are produced by 16 and 18d. • IgY+ lymphocytes develop on day 21 around the time of hatching. • IgA+ lymphocytes first appear in the intestine 3 to 7 days after hatching.

11. Vaccination of 18-day embryonated eggs is commonly employed in the modern poultry industry. • The major vaccine employed is against the Marek’s disease herpesvirus.

12. 13-1-1 Development of Phagocytic Capability • Neutrophils are fully capable of phagocytosing bacteria in the fetal pig at 90 days postconception. • Poor bactericidal activity lasts until 100 days of pregnancy. • Near birth, the phagocytic and bactericidal capacity of neutrophils declines as a result of fetal steroid levels.

13. After birth, macrophages have depressed chemotactic responsiveness, and they are also able to support the growth of some viruses. • Newborn piglets is deficient in some complements. • There are very few pulmonary macrophages in newborn piglets. They appear predominantly a few days later.

14. 13-1-2 The Immune System and Intrauterine Infection • The fetal immune system is less capable of combating infection. • The acquired immune system is not fully functional. • Some infections may be sever or lethal in the fetus. Bluetonge, infectious bovine rhinotracheitis, porcine parvovirus, bovine virus diarrhea, and brucella abortus.

15. Fetal infections commonly trigger an immune response and elevated Ig levels. • The presence of any Ig in the serum of a newborn, unsuckled animal suggests infection in utero.

16. The effects of bovine viral diarrhea virus infection on development of the fetal calf depend on the time of infection

18. Since they are specifically tolerant to BVD, persistently infected calves shed large quantities of virus in their body secretions and excretions and so act as the major source of BVD for other animals in a herd. • The persistently infected calves grow slowly and often die of opportunistic infections, such as pneumonia before reaching adulthood.

19. 13-2 Immune Response of Newborn Animals • Situation:mammals are born into an environment rich in microorganisms after developing in the sterile environment in the uterus. • The young of domestic animals are capable of mounting both innate and acquired immune responses at birth. • The acquired immune system is in progress.

20. The newborn animals tend to produce immune responses skewed toward a Th2 rather than Th1 cytokine pattern. • Over the first months of life, the immune responses usually revert to the balanced adult pattern. • Unless immunological assistance is provided, newborn animals may be killed by organisms that present little threat to an adult.

21. 13-3 Transfer of Immunity from Mother to Offspring • The rout by which maternal antibodies reach the fetus is determined by the structure of the placenta.

29. 13-3-1 Secretion and Composition of Colostrum and Milk

31. 13-3-2 Absorption of Colostrum • In pig, IgG and IgM are preferentially absorbed. • In ruminants, all immunoglobulin classes are absorbed in the intestine. • Permeability is highest immediately after birth and declines after about 6 hours.

32. In piglets, the ability of absorbing immunoglobulins may be retained for up to 4 days. • The amount of IgA in the intestine can be large, a 3-week-old piglet may receive 1.6g daily from sow’s milk.

34. 13-4 Development of Acquired Immunity in Neonatal Animals

35. Local Immunity • The intestinal lymphoid tissues of neonatal animals respond rapidly to an ingested antigen. • Calves orally vaccinated with coronavirus vaccines at birth are resistant to virulent coronavirus within 3 to 9 days.

36. Piglets vaccinated orally 3 days after birth with transmissible gastroenteritis virus (TGE) vaccines develop neutralizing antibodies in the intestine 5-14 days later. • There is an early intestinal IgM response that switch to IgA by 2 weeks.

37. Systemic Immunity • The maternal antibodies inhibit the ability of the newborn to mount its own immune response. • Such an inhibition is B cell-specific and T cell responses are usually unaffected. • One of the simplest is the rapid neutralization of live vaccines by the maternal antibody. • The inhibition results from antibodies binding to B-cell Fc receptors and blocking BCR signaling.

38. Maternal antibodies simply mask the epitopes on vaccine antigens and so prevent their recognition by B cells. • An immune response can be elicited only when maternal antibody titers fall below a critical threshold.

39. Calves begin to generate their own antibodies by about 1 week of age if they fail to suckle. • If calves suckled and thus possess maternal antibodies, antibody synthesis does not commence until about 4 weeks of age.

40. In piglets, colostrum-deprived animals respond well to pseudorabies virus by 2 days after birth. • If piglets suckled colostrum, antibody production does not begin until 5 to 6 weeks after birth.

41. Colostrun-deprived lambs generate IgG1 at 1 week and IgG2 by 3 to 4 weeks. • In colostrum-fed lambs, IgG2 synthesis does not occur until 5 to 6 weeks old.

42. Effect of the presence of maternal antibodies

43. The antibodies acquired by a young animal from its mother is called maternal antibody(母源抗体). • Maternal antibodies is able to inhibit the ability of the newborn to mount its own immune responses. • Very young animals are unable to respond to active immunization using vaccines. • Such an inhibition is B-cell specific and T cell responses are largely unaffected.

44. 13-5 Vaccination of Young Animals • Inhibition of maternal antibodies usually persists for a few months. • Maternal antibodies absorbed from the puppy’s intestine reach maximal levels in serum by 12 to 24 hours after birth.

45. The catabolic rate of the proteins is exponential and is expressed as a half-life. • The half-life of antibodies to canine infectious hepatitis is 8.4 days. • Very few newborn puppies can be successfully vaccinated.

46. Maternal antibodies to tetanus toxin in foals can last for 6 months, and antibodies to equine arteritis virus for as long as 8 months. • Antibodies to bovine virus diarrhea may persist for up to 9 months in calves. • The half-lives of maternal antibodies against equine influenza and equine arteritis virus antigens in the foals are 32 to 39 days.

47. Maternal antibodies effectively block immune response in young foals and calves, even at low levels, leading to ineffectiveness of premature vaccination. • The effectiveness of vaccines increases progressively after the first 6 months of life.

48. BHV: Bovine herpesvirus BVDV: Bovine virus diarrhea virus

49. A safe rule is that calves and foals should be vaccinated no earlier than 3 to 4 months of age followed by one or two revaccinations at 4-week intervals. • The precise schedule will depend on the vaccine used and the species to be vaccinated. • Animals vaccinated before 6 months of age should always be revaccinated at 6 months or after weaning to ensure protection.

50. 13-6 Passive Immunity in the Chick • Newly hatched birds emerge from the sterile environment of the egg and require temporary immunological assistance. • Serum immunoglobulins are actively transported from the hen’s serum to the yolk while the egg is still in the ovary. • IgM and IgA are acquired from oviduct secretions as the fertilized ovum pass down the oviduct.