Immunological variants in children

Children have an immune system that differs from that of adults in several ways; in young children it is fairly immature and cannot provide adequate protection since development requires repeated exposure to new antigens. Several factors can affect the development of a child’s immune system as illustrated in figure 2. A good example for this statement is the results of a recent study conducted at Duke University Medical Centre in relation to peanut hypersensitivity in children. A controlled dose of peanuts was given daily to the patients as the treatment. “At the start of the study, these participants couldn't tolerate one-sixth of a peanut, six months into it, they were ingesting 13 to 15 peanuts before they had a reaction”. ⁸ These results are possible due to immunological changes, like desensitization, that make adaptation and tolerance possible in both children and adults.⁸ An example of this can be seen in the use omalizumab (xolair) to treat moderate to severe persistent allergic asthma caused by allergens in the air. Xolair helps reduce the amount of asthma attacks. ⁹

Neonates are considered to be in a state of immunodeficiency. During the first months of their lives they obtain immunologic protection from their mothers in the form of immunoglobulins (IgG and IgA) that had crossed the placenta in utero, and through breast milk post utero⁴. Breast milk contains macrophages, lymphocytes, granulocytes, antibodies, complement and enzymes which destroy bacteria. Yet, these immunoglobulins are insufficient protection against viral and intra-cellular infections such as cytomegalovirus, Herpes simplex, Listeria and Toxoplasma. It has been shown that the maternal immune system can directly affect the child’s hypersensitivity. An example of this is that maternal cells have been found in an abnormally high number of patients with Juvenile dermatomyositis and these cells contain the mothers HLA that is thought to start the autoimmune response. ⁷ Children who suffer from this muscle damaging disease may also suffer organ failure.

Studies have also shown that newborns posses a depressed number of cells involved in the adaptive immune response and the C3 component of the complement system.³ In a study done in 2006, researchers found low numbers of CD3+ T cells and a decreased level of cytokine activity, which are essential for initiation of the adaptive immune response in neonates.¹ Overall, neonates are more susceptible to viral and intracellular infections due to a deficiency in NK cells and cytotoxic T cells. Although neonates posses functional lymphocytes by around two months of age their antibody production does not reach adult levels until the age of four. This deficiency results in high mortality rates as a result of infection. New research aims to find methods to reduce the morbidity and mortality rates of newborns by reinforcing their dwindling immune system.⁴

Once a child hits puberty, the increasing amounts of gonadotropic hormones induce the secretion of androgens and estrogens, which affect the immune response. Estrogens increase IgG and IgM secretion by mononuclear cells while testosterone may suppress the stress response associated with infection. Another important change that occurs after puberty is the “involution of the thymus”. ⁶ Thymic involution causes a decrease in naïve T lymphocytes resulting in the formation of T cells that are responsive to foreign antigens and have yet to be stimulated by foreign substances. Also, it is believed that involution of the thymus helps to protect the body from autoimmunity disorders.

Questions:

1. During the first months of their lives neonates obtain immunologic protection from:

a. Live vaccines

b. Intravenous infusions of immunoglobulins

c. Blood transfusions

d. Mothers immuglobulins pre partum and breast milk post partum

2. Which immunoglobins are secreted due to estrogen secretion?

a. IgM and IgE

b. IgG and IgM

c. IgG and IgA

d. IgA and IgE

3. Neonates posses functional lymphocytes at about 2 months of age, their antibody production does not reach adult levels until the age of

a. 2

b. 4

c. 10

d.15

4. What environmental factors can affect the development of the immune system?

5. When a child reaches puberty, the secretion of Estrogen causes mononuclear cells to increase production of which two immunoglobulins?

6. Deficiency in which two types of cells would attribute to neonates increased susceptibility to viral and intracellular infections?

References:

1. Engelmann, Ilka *; Moeller, Ulrike; Santamaria, Andrea; Kremsner, Peter G.; Luty, Adrian J.F. Differing activation status and immune effector molecule expression profiles of neonatal and maternal lymphocytes in an African population. Immunology. December 2006; 119(4):515-521

2. Lott, Judy Wright. State of the Science: Neonatal Bacterial Infection in the Early 21st Century. Journal of Perinatal and Neonatal Nursing. January/March 2006; 20 (1): 62-70

3. Firth, Matthew A.; Shewen, Patricia E.; Hodgins, Douglas C. Passive and active components of neonatal innate immune defenses. Animal Health Research Reviews. December 2005; 6 (2): 143-158

4. Ohlsson A, Lacy J. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst. Rev. 2004

5. Jaspan, H.B., Lawn, S.D., Safrit, J.T., et. al.; The Maturing Immune System: Implications for Development and Testing HIV-1 Vaccines for Children and Adolescents. AIDS. 2006; 20:483-494. http://www.medscape.com/viewarticle/524225 . April 10, 2010.

6. Eric S. Lugada, Jonathan Mermin, Frank Kaharuza, Elling Ulvestad, Willy Were, Nina Langeland, Birgitta Asjo, Sam Malamba, and Robert Downing. Population-Based Hematologic and Immunologic Reference Values for a Healthy Ugandan Population. Clin. Diagn. Lab. Immunol., Jan 2004; 11: 29 - 34.

7. Reed, A.M., McNallan, K., Wettstein, P., Vehe, R., and Ober, C. (2004). Does HLA-dependent chimerism underlie the pathogenesis of juvenile dermatomyositis? Journal Immunology; 172, 5041-5046.

8. Burks W. ;M.D. Studies show children can complete treatment for peanut allergies and achieve long-term tolerance. From www.dukemednews.org 2009. Available at: http://www.sciencecentric.com/news/article.php?q=09032026-studies-show-children-can-complete-treatment-peanut-allergies-achieve-long-term-tolerance. Accessed April 14, 2010.

9. 2010 Genentech USA, Inc. and Novartis Pharmaceuticals Corporation. www.xolair.com. Retrieved April 29^th 2010.

Figure 2: Storey M, Jordan S (2008) An overview of the immune system. Nursing Standard. 23, 15-17, 45-56.