A Practical Approach, Second Edition=Ronald D. Ho.pdf

1090 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITION(Ladics et al., 2000). Subsequent histological analysis of the spleens from 10-day old pups indicatedthat there were no germinal centers present either in untreated rats or in rats immunized with theT-dependent antigen, sheep erythrocytes (SRBC). As discussed below, these same studies indicatedthat no anti-SRBC antibody response could be detected in 10-day old rat pups. Taken together,these results suggested that the immune system of a 10-day rat pup is too immature to elicit aprimary response. The phenotypic analysis of the spleen from a 21-day old rat indicated that thenumber of B-cells was comparable to adults, and that the number of T-cells and T-cell subsets wasreduced relative to an adult (Ladics et al., 2000). As discussed below, a number of studies havedemonstrated that rats at approximately 21 days of age are capable of an immune response, butthat it is always less than that seen in an adult animal.DogsShortly after birth in dogs, germinal centers and plasma cells appear in the spleen and lymph nodes(Yang and Gawlack, 1989; Felsberg, 1998), and the thymus undergoes rapid postnatal growth (Yangand Gawlak, 1989; Somberg et al., 1994). The phenotype of the lymphocyte subpopulations inneonatal dogs differs significantly from that observed in adult dogs (Felsberg, 1998, Somberg etal., 1994; Felsberg, 2002). During the first 16 weeks, there is a gradual decline in the proportionof peripheral B-cells and an increase in the proportion of peripheral T-cells to normal adult levels,which occurs between 2 and 4 months of age. Thereafter, the proportion of B- and T-cells remainsfairly constant throughout the life of the dog. Other age-related differences in lymphocyte subsetsinclude the following: considerably higher proportions of CD4+ T-cells during the first six months,a resultant high CD4:CD8 ratios during the same time period, a decline in the proportion of CD4+at 10-12 months; CD8+ T-cells increasing to normal adult levels during the same time with aresultant normalization of the CD4:CD8 ratios (1.5 – 2.0). Finally, during the neonatal and immediatepostnatal period, greater than 90% of the peripheral T-cells are CD45RA+ (naïve) T-cells(Somberg et al., 1996; Felsberg, 2002). After 4 months of age, the relative frequency of CD45RA+T-cells declines such that only 40-50% of the peripheral T-cells in adults are CD45RA+. Interestingly,very similar age-related changes were observed in healthy children and adults (Denny et al.,1992; Erkellar et al., 1992), an observation consistent with the recognition that the immune systemsof dogs and humans are at a similar stage of development at birth.Although most indicators suggest that the development of the immune systems of dogs andhumans are very comparable, there is one important distinction that does impact on the respectivepostnatal development of the immune systems (Felsberg, 2002). Humans possess a hemochorialplacenta in which the blood of the mother is in direct contact with the trophoblast, thereby permittingdirect entry of maternal IgG into the fetal bloodstream. In contrast, dogs have an endotheliochorialplacenta with four structures separating the maternal and fetal blood – the endothelium of theuterine vessels, the chorion, mesenchyme (connective tissue) and the endothelium of fetal tissues.These four layers of tissue separating the maternal and fetal circulation in the dog limit the in uterotransfer of maternal IgG to the fetus. Ultimately, only 5 to 10% of maternal antibody in the dogis obtained in utero through the placenta with the majority being obtained via the colostrums duringthe first 24 hours after birth (Felsberg, 1998). The levels of serum IgG in newborn puppies thatreceive colostrums approach those levels found in adults. It is important to emphasize that the halflifeof maternal antibody in the dog is approximately 8.4 days, so the average protection frommaternal antibody in the neonate is 8 to 16 weeks. Following the decline in maternal IgG, there isa gradual increase of all three major classes of immunoglobulin, with IgM and IgG reaching normaladult levels by 2-3 months of age, and 6 to 9 months of age, respectively. As in other species, thesynthesis of IgA lags behind the other isotypes and doesn’t reach normal adult levels until approximatelyone year of age.© 2006 by Taylor & Francis Group, LLC