Worldwide, overweight/obesity and associated chronic diseases such as type 2 diabetes, have reached epidemic proportions. Statistics show that overweight/obesity and chronic disease is prevalent amongst adults and children in South Africa. In addition to chronic disease/non-communicable diseases, overweight/obesity has been shown to alter immune and sympathetic activation. There is limited information on immune function (mucosal) and sympathetic activation on children both internationally and nationally and in particular investigating these parameters using non-invasive methods such as salivary biomarkers. The aim of this thesis was to investigate the levels of salivary biomarkers of immune function and sympathetic activation in children and determine the association with overweight/obesity, cardiorespiratory fitness (CRF) and increased physical activity (PA). Methods This thesis is divided into six chapters. These include an introductory chapter (Chapter One), a review of the literature (Chapter Two) and then three chapters that are written in article format and that have each been submitted to accredited journals for publication. Chapter Three is a review article that discusses salivary biomarkers in children as they relate to exercise, PA and obesity. Chapter Four is a study that examined salivary biomarkers of mucosal immunity and sympathetic activation as predicted by age, body composition and cardiorespiratory variables in one hundred and thirty-two black South African children (age 10.05 ± 1.68y, 74 females, 58 males). Chapter Five is a study that investigated salivary biomarkers of mucosal immunity and sympathetic activation in response to 12 weeks of soccer training in thirty-four black male South African children (11 – 13y) from a youth football training academy. Chapter Six includes a summary of the research findings, conclusions and well as recommendations for future research. A review of the literature revealed that participation in regular moderate intensity PA or exercise appears to enhance mucosal immunity (increases salivary IgA (sIgA)) in preadolescent children. In contrast, poor fitness and inactivity as well as strenuous training appear to compromise the mucosal immune system thereby increasing the risk of upper respiratory tract infections (URTIs). Children reporting higher levels of body fat and with a greater BMI appear to have lower sIgA levels and a greater incidence of infections. The limited research examining salivary C-reactive protein (sCRP) suggests a strong association between poor cardio-respiratory fitness (CRF) and/or overweight/obesity and inflammatory status in children based on elevated sCRP levels. Research surrounding salivary alpha-amylase (sAA) indicates that exercise can result in a marked increase in sAA as seen by an increase sympathetic activity via increased adrenergic activity in the salivary glands. The limited research suggests exercise may also pose a high stress on young athletes as seen with an increase in sAA. Additionally it appears that BMI may be a strong predictor of stress-induced sAA increases in children. Greater hypothalamic pituitary adrenal (HPA) axis response, as seen by increases in salivary cortisol, appear to be influenced greatly by increases in obesity. Higher salivary cortisol secretions have been observed in obese versus lean children in response to exercise. School study: The outcomes of the one-way ANOVAs examining the differences by body mass index (BMI) categories showed there were significant differences in weight (F = 83.64, df = 2, 129, P < 0.0001), BMI (F = 193.36, df = 2, 129, P < 0.0001), waist-to-hip ratio (F = 193.36, df = 2, 129, P < 0.0001), body fat percentage (F = 336.98, df = 2, 129, P = 0.0001), SBP (F = 5.72, df = 2, 129, P = 0.0042), DBP (F = 291.76, df = 2, 129, P < 0.0001), VO2max (F = 521.00, df = 2, 129, P < 0.0001), sAA concentration (F = 17.05, df = 2, 129, P < 0.0001), sAA secretion rate (F = 15.15, df = 2, 129, P < 0.0001), sIgA concentration (F = 11.30, df = 2, 129, P < 0.0001), and sIgA secretion rate (F = 8.08, df = 2, 129, P = 0.0005), between children of different BMI categories. According to the CDC-BMI-for-age standards, the participants were grouped into the following CDC-BMI-for-age categories: normal weight (< 85th percentile), overweight (≥ 85th percentile to < 95th percentile), and obese (≥ 95th percentile) (Ogden and Flegal, 2010). Tukey’s post hoc analyses revealed that obese children had significantly (P < 0.01) higher weight, BMI, body fat percentage, DBP, SBP, sAA concentration and secretion rate, compared to overweight and normal weight children, as well as a significantly lower aerobic capacity (VO2max) than both normal (P < 0.001) weight and overweight (P < 0.05) children. In addition, sIgA concentration and secretion rate were significantly lower between normal weight and obese children (P < 0.01). Multiple linear regression revealed that BMI, DBP and VO2max predicted sAA. BMI (P = 0.04) and DBP (P = 0.04) were found to be independent predictors of sAA concentration. Age and BMI category predicted sIgA secretion rate. BMI category (P = 0.0006) was found to be an independent predictor of sIgA secretion rate. Soccer study: Significant differences after 12 weeks of soccer specific training were found to be significant between pre vs. post for BMI (P =0.034), waist-to-hip ratio (P = 0.046), age (P < 0.0001), height (P < 0.0001), body fat % (P < 0.0001) and LMM (P < 0.0001). Decreases in BMI, waist-to-hip ratio, body fat % and LMM were found while age and height increased throughout the 12 weeks. Significant differences were also found between sIgA secretion rate pre vs. post training (P =0.025) as increases in these values pre to post were observed. Conclusions The results from the studies on the school children and soccer players suggested that mucosal immune function and sympathetic activation appear to be affected by body composition, CRF and chronic exercise training. The main findings for the school study revealed that BMI, DBP and VO2 predict sAA and that age and BMI category predict sIgA. This study also found that obesity (based on BMI) has a major role to play and that obese children have elevated sAA, lowered sIgA, and poor CRF. The finding of an increase in sIgA secretion rate in the soccer study suggested that a structured 12 week exercise programme can elevate mucosal immune function in youth soccer players. The underlying mechanism responsible may be an exercise-induced increase in the transport of sIgA across the mucosal epithelium and/or enhanced production of IgA in the mucosa via mediating cytokines. The literature review demonstrated that PA and overweight/obesity may have an impact on salivary biomarkers of mucosal immunity and sympathetic activation in children, however further research with regards to optimal intensity, duration and modality need to be assessed in the pre-pubescent population.Physical activity, obesity, immunity, neuro-endocrine, children, salivary biomarkers, sympathetic activation. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.