Anatomy and Physiology

IMMUNE SYSTEM DEVELOPMENT The immune system begins very early in fetal development with the origin of bloodformation in the third week of gestation. In the fourth week of gestation the thymus forms. Thethymus helps to mature and develop white blood cells so that they can play a key role in fightinginfections. By the eighth week of gestation, T cells, B cells, and natural killer cells can all befound in the thymus. T cells, which make an important component in cell-mediated immunity, are formedsolely in the thymus. B cells, which are the precursors of antibody producing cells, are firstproduced in the liver but by 12 weeks gestation move into the bone marrow where it remains.Natural killer cells, which are cytotoxic cells that have the ability to attack viruses, mature in thethymus. Interestingly, greater concentrations of natural killer cells are found in the peripheralblood of newborns and the newborn usually has adult levels of these cells at birth, but theydiminish rapidly. Orlando Regional Healthcare, Education & Development Copyright 2004 Page 4 Neutrophils are relatively numerous in both the term and pre-term infant. A neutrophil isa type of white blood cell that defends the body from organisms that cause infection. The stagesof neutrophil development, from immature to mature, are myeloblast, promyelocyte, myelocyte,metamyelocte, band, and segmented neutrophil. When an infection is present, the neutrophilsmigrate out of the capillaries and into the infected site, where they ingest and destroy thepathogens causing the infection. The amount of circulating neutrophils in the newborn peaksaround 12 hours after birth and then starts to decline to normal levels. Even though a largenumber of circulating neutrophils can be found in the newborn, the bone marrow storage pool of neutrophils at birth is only 20% to 30% of the circulating pool in adults. Differences in Immune Responses in Full and Preterm Infants
Immune System Component Immunoglobulin G Full Term Infant Preterm Infant

Complete placental transfer, concentrations comparable to mother Concentrations of T and B cells comparable to those in adults with normal response to antigens

Incomplete placental transfer, concentrations decreased Concentrations of T and B cells comparable to those in adults with normal response to antigens

Lymphocytes

Complement Neutrophils

50%-75% of concentration in adult Elevated numbers at birth, with impaired functional ability

Decreased concentration Elevated numbers at birth, with impaired functional ability

Anatomy and Physiology

Monocytes Normal number at birth but have impaired chemotaxis Normal number at birth but decreased function Concentration similar to adult level, but have diminished cytotoxic effects Normal number at birth but have impaired chemotaxis Normal number at birth but decreased function Concentration similar to adult level, but have diminished cytotoxic effects

Macrophages

Natural Killer Cells

Immune System Physiology Despite the immune system and immune system components, early development duringgestation the newborn still remains vulnerable to infections after they are born because of theimmaturity of their immune system. A newborn has a poor response to invading pathogens. This immune response willgradually improve with age. During the initial postpartum phase, the infant relies on maternalantibodies and the mothers breast milk, which is rich with immunoglobulins. When apathogenic organism overcomes the infants defenses, infection and sepsis result. Sepsis isdefined as the presence of microorganisms or their toxins in blood or other tissues. Newbornsepsis is still one of the most significant causes of neonatal disability and death today. Reviewing the functions of the infants immune system will help provide a better understanding of the interaction between the pathogenic organisms and the newbornssusceptibility to infection. Infections occur when the infant comes in contact with a pathogenicorganism. The organism, whether it is a virus, fungus, or bacteria, enters into the infants bodysystem and begins to multiply. The infants immune system response to an organism is divided into three phases. Thefirst phase is the primary or nonspecific phase, which occurs immediately following the infantsinoculation with a pathogenic organism. During this phase, there is a migration of the neutrophilsto the primary site of the infection. The neutrophils enter into the cells through membrane filtersand adhere to the pathogen. Ingestion and destruction of the invading organism then takes place. The next phase in the immune response is called the secondary phase or the specific response phase. During this phase, there is interaction of T and B cells to help develop immunoglobulins or antibodies to protect the infant from the infection. There are three major types of immunoglobulins: Immunoglobulin G (IgG), Immunoglobulin M (IgM), and Immunoglobulin A (IgA). Immunoglobulin G is the major immunoglobulin of the serum and interstitial fluid. It provides immunity against both bacterial and viral pathogens. It starts to cross the placenta and enter into fetal circulation around 30 weeks gestation and continues until
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the 40 week. Term infants have IgG levels that are equal to or exceed maternal levels.
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Since IgG is not transferred until around the 30 week of gestation, the preterm infant does not have this protective barrier. Preterm infants are thus at higher risk for infections.

Anatomy and Physiology

Research has shown that there are also decreased levels of IgG in post-term and small for gestation age infants, which suggest that there may be some inhibition of transfer with placental damage. Immunoglobulin M does not cross the placenta thus, little or no IgM is transferred to the fetus. This lack of IgM increases the infants susceptibility to gram negative infections. The infant does however begin synthesis of this immunoglobulin very early in their fetal life. Levels of IgM have been detected around 30 weeks gestation with higher levels detected when there is an intrauterine infection present. Immunoglobulin A is the most common immunoglobulin found in the gastrointestinal tract, respiratory tract, human colostrum, and breast milk. IgA does not cross the placenta, and intrauterine synthesis is minimal. Levels of IgA are usually not detected until the infant is around 2 to 3 weeks old. The last immune response is the tertiary phase. This phase provides long-term immunity against the organism. During the second phase, the B cells produce memory cells that recognize the invading pathogen on subsequent exposures. These memory cells recognize the invading organism and cause them to be neutralized, preventing the infant from becoming sick again. Although adequate numbers of B cells are present at birth, antibody production is diminished in the neonate due to a lack of uterine exposure to foreign pathogens.