Abstract. Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) characterized by inflammatory demyelination, axonal injury, and progressive neurodegeneration [1–4]. Although historically regarded as a T cell–driven disease, accumulating evidence demonstrates that MS arises from complex interactions between adaptive and innate immune systems, genetic susceptibility, and environmental exposures [5,10]. Aberrant activation of autoreactive lymphocytes, dysregulated cytokine signaling, breakdown of immune tolerance, and sustained microglial activation collectively drive CNS pathology [1,18–20]. This review provides an in-depth and updated analysis of the immunological mechanisms underlying MS pathogenesis, with particular emphasis on immune tolerance failure, lymphocyte trafficking, antigen presentation, neuroimmune crosstalk, and chronic inflammatory neurodegeneration.