Despite modern prevention and treatment therapies, malaria morbidity and mortality is on the rise. A major roadblock to malaria eradication is the failure of current vaccines to induce long-lasting disease protection in malaria-endemic children, who carry the highest burden of severe illness and mortality. Central to the slow acquisition of long-term anti-parasite immunity and low vaccine efficacy is the development of anti-disease regulatory immune cell responses. This thesis aims to investigate the global immune regulation of peripheral immune cells during blood-stage Plasmodium falciparum (Pf ) malaria and characterise the multi-functional activation of γδ T cell innate- and adaptive-like immune responses in malaria. To do this, we implemented a number of innovative strategies to characterise the transcriptional and protein profiles of peripheral immune cells in primary malaria infection models. [...]