The diagnosis and treatment of tuberculosis rely on a deep understanding of the pathobiology and immune responses. This study aimed to identify potential immune response mechanisms by integrating gene expression analysis with immune cell distribution profiling to characterize the immune phenotypes of active tuberculosis (ATB) and latent tuberculosis infection (LTB). Differentially expressed genes (DEGs) between ATB or LTB and controls were identified using the GSE19491 and GSE107994 datasets. A total of 273 and 105 immune-related DEGs were identified in ATB and LTB through ImmProt database, respectively. Immune-related DEGs specific to LTB were mainly enriched in the MAPK signaling pathway, Ras signaling pathway. Furthermore, random forest analysis identified HLA-DRB5 and IRF1 as showing diagnostic potential in ATB, LCN10, SHC1, IKBKG, RETN, and SOS1 showed importance in LTB. Flow cytometry detected significantly higher levels of macrophages M0 in ATB compared to LTB and controls, while other types of immune cells showed significant increases in LTB. The levels of marker genes were validated by RT-qPCR and Western blot, as well as single-cell data in ATB and LTB. The findings of this study provide potential biomarkers for the diagnosis of tuberculosis and may facilitate the development of more effective treatment strategies.