GENETIC AND ANTIGENIC VARIABILITY IN GIARDIA LAMBLIA

The aim of the proposed project is to characterize the cellular immune response changes in infants and young children, associated with symptomatic and asymptomatic infections with Giardia lamblia, Cryptosporidium and E. coli. As previous data was obtained from cross- sectional studies, several interrelated questions remain to be answered; which cellular immune changes predispose to gastrointestinal infection in general and diarrhea in particular? Which cellular immune profiles predispose to persistent diarrhea and what factors predispose to the acquisition of such profiles? And how do cellular immune changes resulting from infection with specific organisms affects the clinical response to future infection with the same organism, or to infections with other enteric agents? Peripheral blood lymphocytes obtained prospectively from children will be analyzed for changes in lymphocyte subsets and their plasma will be analyzed for the level of various cytokines and of soluble lymphocytes receptors both before and after infection. The development and maturation of lymphocytes with a 'memory' phenotype will be determined, and the mobilization of T-lymphocytes with different T-cell receptor chains (tau/delta TCR) in gastrointestinal infections examined. The effect of gastrointestinal infections on natural killer cells will be also assessed. While this project assesses the parameters of cellular immunity, in children from the Project 1 cohort, and in children hospitalized for diarrhea (Project 2), the humoral immune response of these children will be assessed by Cores 3 and 4. With the enteric organisms defined in Core C and the Giardia lamblia strains, characterized in Projects 3 and 5 it will be possible to assess the effect of age, environmental factors, nutritional status, genetics, and previous enteric infections on the acquisition and expression of cellular immunity in infants and young children. In addition, knowledge of the immune status prior to infection will enable us to define the profile predisposing to future enteric disease.