response, have greatly advanced our knowledge of the composition of the immune system and mechanisms of immune regulation. The use of other species has provided further information on factors regulating immune responses, and also revealed there are species differences in the composition of the immune system that need to be taken into consideration when attempting to understand the immune response to a pathogen in the target species (Davis and Hamilton, 1998). This is especially important for studies in ruminants (Davis et al., 1996; Goddeeris, 1998; MacHugh et al., 1993; Wijngaard et al., 1994).

Three major lineages of lymphocytes have been identified: αβ- and γδ-T-lymphocytes, and B lymphocytes. The subset composition of the αβ-T and B lymphocyte lineages is similar in most species (Goddeeris, 1998). However, the composition of the γδ-T-lymphocyte lineage differs. In most species, there is one lineage of γδ-T-lymphocytes that is present in low frequency (three to five percent) in peripheral blood, but widely distributed in mucosal tissue at sites of entry of pathogens. There are two lineages of γδ-T-lymphocytes in ruminants and other Artiodactyla (pigs and camelids) that differ in phenotype and tissue distribution (Davis et al., 1996, 1998, 2000; Goddeeris, 1998; MacHugh et al., 1998). One population with a phenotype similar to γδ-T-lymphocytes in humans and mice is present in blood (three to five percent) and tissues in comparable proportions, except in the spleen where they may comprise 30 percent or more of the lymphocytes present (Davis et al., 1996). The second population is distinguished by the expression of a unique molecule, workshop cluster 1 (WC1). It differs from the WC1− population in frequency in peripheral blood and in the pattern of trafficking, potentially associated with differences in function (Wilson et al., 1998, 1999). The WC1+ population may comprise 30 to 50 percent of lymphocytes in peripheral blood of young animals. Except for the spleen, the WC1+ and WC1− γδ-T-lymphocytes are present in similar proportions in secondary lymphoid tissue and in epithelial tissues at points of entry of pathogens (Wyatt et al., 1994, 1996). Additional smaller subsets of lymphocytes have also been identified, including natural killer cells (NK). Limited information is available on the role of these subsets and γδ-T-lymphocytes in host defense (Kaufmann, 1996). However, it is thought that γδ-T-lymphocytes and NK cells may play a role in first line of defense against infectious agents (Kaufmann, 1996).

The development of a protective immune response is complex (Seder and Hill, 2000; Van Parijs and Abbas, 1998). It involves the interaction of multiple cell types following exposure to a pathogen. In general, there are four phases to the response: (1) antigen recognition following encounter with a pathogen, (2) increase in the frequency of antigen-specific lymphocytes involved in cell-mediated immune (CMI) response and humoral immunity, (3) contraction of the responding populations through apoptosis following control of the infection, and (4) appearance of memory lymphocytes. Protective immunity is dependent on the development and maintenance of memory cells following encounter with pathogens. Immunity is lost if the concentration of antigen-specific memory cells drops below a threshold level needed for a rapid recall