Technical Abstract: Mycobacterium tuberculosis and M. bovis are closely related (>99% genetic identity), inducing similar host responses and disease expression upon infection. There is a rich history of co-discovery in the development of control measures applicable to both human and bovine tuberculosis (TB) including skin-testing procedures, BCG vaccination, and interferon-gamma release assays. The calf TB infection model offers several opportunities to further our understanding of TB immunopathogenesis. Recent observations include: correlation of central memory immune responses with TB vaccine efficacy, association of SIRP alpha + cells in ESAT-6:CFP10-elicited multinucleate giant cell formation, early gamma delta T cell responses to TB, anti-mycobacterial activity of memory CD4+ T cells via granulysin production, association of specific antibody with antigen burden, and suppression of innate immune gene expression in infected animals. Partnerships pairing researchers with veterinary and medical perspectives should provide mutual benefit to TB research.