This is a Reprint of the first edition of the Special Issue on "Cellular and Molecular Mechanisms in Immune Regulation" published by the journal Cells in 2024-2025. The reprint starts with a review of the latest advances in molecular mechanisms of immunity and the effect of X chromosome loss in immune function. Next, we focus on autoimmunity by exploring the use of circular RNAs as biomarkers in multiple sclerosis and the role of circulating T cell subsets in Type 1 diabetes. We conclude reviewing the part played by lipid biosynthesis metabolism in the inflammatory response mediated by microglia in neurodegeneration and wound healing in the central nervous system. The importance of Immune regulation for preventive medicine is highlighted by a review on the interactions of T follicular helper cells and B cells and their role in the control of viral infections and vaccine design. Next, we explore how immune cell populations affect the prognosis of cancer patients treated by Immunotherapy using immune check point inhibitors. We conclude this part with an emphasis on tissue resident memory T cells (TRMs) and their potential in the control of cancer metastasis. The Special Issue concludes with articles highlighting the interactions between the environment and the immune system, specifically on the generation of tolerogenic dendritic cells mediated by oxygen tension in tissues and exposure to ultraviolet light (UV) on the skin. Thus, this reprint provides a glimpse of the multi-cellular immunoregulatory networks implicated in autoimmune diseases, infection and cancer as well as during normal interactions with the environment.