Doctoral Dissertation ImprovementGrant: Immunocompetence and the Hygiene Hypothesis

University Of Washington, Seattle WA

Investigators

Abstract

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.