Puppies

Development and function of complement pathways, antigen-presenting cells (APCs), phagocytic cells, and other pathways of the innate immune system have not been well characterized in puppies. However, one study observed increased phagocytic activity of neutrophils and macrophages in neonatal puppies compared to young adult dogs, suggesting there may be adequate function of phagocytic cells in puppies to help with the first line of defense against potential pathogens. In humans and mice, APCs have reduced ligand expression, which is necessary for stimulating specific immune responses, compared to adults. Although this has not been specifically evaluated in dogs, APCs may not be mature in neonatal puppies.

Immunologic development of the lymphoid system is incremental in all species. As a generality, the shorter the gestation, the less developed the immune system is at birth. In puppies, immunologic development is an early event, beginning in midgestation with lymphocytes present in circulation at 25 days of gestation (Figure 14-1). Thymic development begins on day 27 of gestation, followed by lymphoid infiltration into secondary lymphoid organs, including spleen and lymph nodes, on days 45 to 52 of gestation. Thymic development appears histologically normal by day 45 of gestation. In contrast, splenic and lymph node architecture is not completely developed in the fetus and lacks germinal centers and B cell follicles until shortly after birth.

Figure 14-1 Immunologic development of the dog.

At birth the numbers of peripheral lymphocytes increase and are initially composed of primarily B cells and CD4+ T cells with lower numbers of CD8+ T cytotoxic lymphocytes. The majority of T cells, almost 90%, are naive at birth compared to only 40% at 4 months of age, indicating progressive maturation of the T cell population during this time. The number of B lymphocytes in neonates is much higher than adults, but after the initial increase, B cell lymphocyte numbers decline until 16 weeks of age. The high proportion of B lymphocytes in newborns likely represents early B cell stimulation and maturation in response to new antigens. T cytotoxic lymphocytes are important in cell-mediated immunity and are low at birth. This finding may lend support to human and mouse studies showing downregulation of cell-mediated immunity in neonates. Because T cytotoxic lymphocytes are important for detecting and inactivating intracellular pathogens, the low numbers of T cytotoxic lymphocytes at birth may predispose a newborn to intracellular viral or bacterial infections. T cytotoxic lymphocytes increase steadily with age, whereas CD4+ T lymphocytes maintain at relatively steady numbers from birth to adulthood.

Knowledge of the distribution of peripheral lymphocytes is important to help determine if there are areas of immune deficiency in the neonate; however, function is another defining characteristic. Functional lymphocytes have been observed in the fetus, which is able to respond to antigens after lymphoid tissue develops in the last third of gestation. However, the antibody responses are variable and not as pronounced when compared to adults. Functional and specific lymphocyte responses are also present at birth, but similar to the fetus, antibody responses are often only a portion of the adult antibody response. One study observed adequate antibody response in day-old puppies immunized with a modified live canine parvovirus strain, suggesting some antigens may elicit an adequate antibody response, or some puppies have a higher level of immune development. In general, it is recognized that domestic animals are immunocompetent at birth; however, complete maturation of the immune system occurs postnatally.

Kittens

Development of the kitten’s first line of defense, the innate immune system, including complement pathways, APCs, and other pathways of the innate immune system has not been well described. Neutrophil function has been evaluated, and phagocytic function is present at birth to help combat initial potential pathogens but is only a portion of adult response. The observed phagocytic response is independent of colostrum ingestion and matures to an adult response by 8 weeks of age. Based on human and mouse studies, it is speculated that APCs may also have reduced function in kittens; however, this hypothesis requires further evaluation.

Unlike the dog, there are only a few studies published discussing lymphoid development from the fetus to six months of age in kittens. Similar to the dog, lymphocytes have been detected in fetal circulation at approximately 25 days of gestation. Lymphocytes have also been detected in the thymus, spleen, and liver at between 28 to 52 days of gestation supporting fetal development of lymphoid tissue. In late gestation, there is a significant increase in peripheral T lymphocytes, which remain elevated after birth becoming the primary circulating lymphocyte in the adult. CD4+ T lymphocytes are present in higher numbers than CD8+ T lymphocytes, resulting in a high CD4:CD8 ratio at birth. The low numbers of CD8+ T lymphocytes at birth may be an effect of the queen’s immune status during pregnancy downregulating cell-mediated immunity, although this has not been evaluated in cats. CD8+ T lymphocytes begin to increase through 8 weeks of age, lowering the CD4+:CD8+ ratio. B cell numbers increase right after birth until 4 weeks of age, likely representative of maturation of the humoral immune response, then steadily decrease to adult values. The timeline for reaching adult distribution of lymphocyte subsets has not been definitively established but is thought to occur before 12 months of age. Similar to the puppy, kittens are immunocompetent at birth but appear to have restricted immune responses compared to adults. Antigenic stimulation of the fetus has not been documented in kittens so conclusions about fetal response to antigens are unknown.