Bovine respiratory diseases are widespread and too costly disease impacting contributes to economically essential diseases like mastitis and pneumonia worldwide. The present study aimed to explore the influence of M. bovis field strain 07801 on the status of PBMCs in the challenged cattle group and the immunized one. For this aim, the PBMCs proliferation, apoptosis, and cytokine profile changes were determined. In this study, M. bovis strain Mb 07801 and reference strain PG45 were used; ten calves (2-3 months old) were arranged into two groups (5 calve each): 1) PBS-challenged group (with M. bovis 07801 at about 10¹⁰ CFU/ml), and 2) immunized group (by Inactivated M. bovis 07801); both groups were treated nasally and intra-tracheal. Blood samples were obtained from both groups and examined for PBMCs proliferation and apoptosis, as well as serum cytokine profile, before infection and at day zero and days 7, 14, 21, and 36 post bacterial treatment. The results revealed that M. bovis strain (07801and PG45) antigen increased the proliferative response of the stimulated PBMC compared with the unstimulated cells and ConA-alone stimulated. The PBMC apoptosis showed a non-significant increase in both challenged and immunized groups compared to the negative and positive control (treated with apoptosis inducer) groups. Besides, the levels of cytokines profile showed a significant up-regulation in IFN-γ, IL-4, IL-2, IL-18, TNF-α, IFN-α, IL-6, IL-10 IL-1β, and IL-13, in both groups, except IL-4 and IL-18 those recorded a down-regulation in the immunized group at days 7,14, 21, and 36 post-M. bovis infection. In conclusion, immunization markedly ameliorated the immune deterioration induced by M. bovis strain 07801.