This project evaluates the hypothesis that the developing immune system adapts to local infectious disease conditions. Immune responses come in two major forms: T-helper (Th) types 1 and 2. Th1 responses fight viruses and bacteria, while Th2 responses fight larger, extracellular, pathogens, like worms and flukes. Th1 and Th2 responses are counter-regulated, or traded-off against each other. Responding to more frequent viral and bacterial infections in the first year of life with a stronger Th1 bias could "prime" the immune response for fighting such pathogens throughout life. While immune responses protect against infection, they can also cause disease. Th1 responses can cause autoimmune disease when mistakenly mounted against host tissue (for example, in rheumatoid arthritis, the immune system attacks the body's joints). Th2 responses can cause allergy when mounted against otherwise harmless particles (for example, pollen or peanuts). Research has repeatedly shown that people with greater exposure to viruses and bacteria (Th1-stimulating pathogens) in their first year of life have lower risk of allergy (a Th2-mediated disorder). Drawing on this well-documented association in allergy epidemiology, this project investigates the association between family size and immunocompetence among children in Tanzania. Family size is a proxy for early life exposure to viruses and bacteria (siblings are a common source of such infections during the first year of life). The PIs use the Candin skin test to measure immunocompetence (the test introduces pathogen surface particles under a subject's skin if a Th1 response is mounted, a bump appears at the test site). If early life infectious diseases stimulate stronger Th1-mediated responses, having more siblings should increase a child?s likelihood of being immunocompetent.
This research has important implications for public health and infectious disease susceptibility. If immune system development is "primed" by early life infections, children who are sheltered from infection during the early years of immune system development may be more vulnerable to infection with such pathogens later in life. This project also contributes to the training of a female graduate student.
This research evaluated the association between exposure to infectious agents during early life and the function of the immune system during childhood. We tested they hypothesis that early exposure to infectious agents (e.g., bacteria and viruses) "primes" the developing immune system, promoting stronger responses to these agents in later years. This hypothesis was tested in Kilimanjaro, Tanzania, where infectious diseases during childhood are common and understanding immune function is particularly important. 315 2-7 year old children participated in the project. Parents provided information about the child and his or her family, including family size, household composition, and early life health history. From this information, three factors were used to assess early life exposure to infectious agents: household size (siblings are a common source of disease transmission among young children), a history of hospitalization during infancy (<1 year) for an infectious disease (mostly pneumonia and malaria), and BCG vaccination against tuberculosis. We used the Candin skin test to assess immune responses among the children sampled. The Candin test introduces a small amount of protein from a common infectious agent, Candida albicans, under the skin. If a child mounts an immune response, a bump is visible at the test site after ~24 hours. The bump indicates that the child's immune system is competent to mount an immune response to an infectious agent. Our results show that children from larger households, children who were hospitalized during infancy with an infectious disease diagnosis, and children with a BCG vaccination scar were more likely to have positive responses to the Candin skin test. Thus, among children in Kilimanjaro, Tanzania, exposure to infectious agents in early life is associated with a higher probability of mounting immune responses to such agents later in childhood. This supports the hypothesis that exposure to infectious agents in early life may "prime" the developing immune system to better respond to infection throughout life. These findings are preliminary. Very little research has investigated the role of infectious disease during infancy in the development of competent immune responses to pathogens. Our results suggest that infectious agents may promote the development of healthy immune function, but are far from definitive. Additional longitudinal research will be needed to verify and expand on our findings.
