The purpose of the proposed research is to identify and quantify the principal determinants of measures of immune

function of a wild mammal, Mus musculus. The immune function of wild animals, and its control, is very poorly

understood, despite the key role that immune function plays in their fitness. We do not know what immune responses wild

animals make, nor what affects and controls this.

Wild animals are continually exposed to infections, against which they make immune responses. This inter-play between

exposure to infection and retaliatory immune responses ultimately determines the fitness and survival of individual

animals. Animal immune function is also central to host-pathogen population dynamics. Immune responses are the key

link between, and mediator of, these processes but are poorly understood in the natural environment. Understanding

what controls immune function, and the effects of immune function, is central to understanding the consequences of

infection for wild animals (as well as for their pathogens). Our work will exploit the deep laboratory based knowledge and

understanding of murine immunology and use a wide range of validated tools to - for the first time - discover what immune

responses a wild animal makes and what controls this.

Laboratory studies have shown the many factors that may affect immune responses (sex, genetics, nutritional status, age,

infection status etc.) but which factors actually do affect immune function, nor their relative roles and importance, in wild

animals is not known.

In a pilot project that investigated the immune function of wild caught M. musculus, we found that the immune responses

of these animals differed substantially from each other (and differed markedly from laboratory mice).

We now to propose to undertake a full study of the immune function of wild mice and to partition the effect of different

intrinsic and extrinsic factors on M. musculus immune function. The specific objectives of the proposed work are to:

1. Make measures of immune function of wild M. musculus,

2. Quantify the effect of extrinsic and intrinsic factors on measures of immune function, and

3. Experimentally test causality of key explanatory factors of immune function.

To do this we will undertake a cross-sectional survey of wild M. musculus populations. We will assay the humoural and

cellular, innate and adaptive immune function of the mice. This will address objective 1. At the same time we shall

measure likely key intrinsic factors (sex, genetics, reproductive status, hormone status, body condition, infection status)

and extrinsic factors such as season and location. We will then seek to explain how the intrinsic and extrinsic factors (and

combinations of these factors) affect immune function, particularly using structural equation modelling. This will address

objective 2. To move from association to causality, we will then experimentally test these findings in wild mice, which will

address objective 3.

Understanding the control of immune responses and their relationship to other life-history aspects is central to ultimately

understanding fitness of wild animals. This information is key to understanding how wild animals deal with their existing

range of infection challenges and the effects that novel and emerging infections, or other changes in their environment,

will have on them. This is particularly pressing given the current high rate of environmental change.