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Despite the inability of the BALB/c mice to acquire resistance against Ixodes ricinus nymphal attachment after multiple infestations, immune responses in naïve animals to tick infestations are inevitable. To investigate this, our study aimed to characterise the in vivo immune response of tick-naïve and nymph extract immunised BALB/c mice infested with I. ricinus nymphs. This was done by characterising B and T-lymphocyte populations in the draining lymph nodes and spleens of these BALB/c mice. Additionally, the T-helper 2/T-helper 1 cytokine ratios from in vivo isolated lymphocytes from tick-infested mice were evaluated. Results indicate that immunising BALB/c mice with nymph extract does not provide protection to subsequent tick infestations. Additionally, a B-cell population (CD45+ CD19+ IgM+ CD27+ CD80+) was uniquely up-regulated during tick feeding and significantly down-regulated in immunised mice at 9 and 8 days post infestation, respectively. Regarding T-cells, no significant differences in the numbers of CD45+ CD3+ CD4+ T-helper cells were noted in tick-naïve or nymph extract immunised mice compared to their controls. Concurrently, a T-helper cell subset (CD45+ CD3+ CD4+ CD195+ CD184-) was significantly decreased in tick-naïve mice at 12 days post infestation. A slight significant decrease in T regulatory cells (CD45+ CD3+ CD4+ CD25+) was observed in only nymph extract immunised mice. The results presented in this study are the first to describe populations of T and B-lymphocytes in the lymph nodes of tick extract immunised and tick-naïve mice in response to infestation. Although additional studies with a finer …