Space exploration presents unique physiological challenges, with immune dysregulation emerging as a critical concern for astronaut health during long-duration missions. The immune system, a highly adaptive network, is particularly sensitive to the stressors of spaceflight, including microgravity, cosmic radiation, disrupted circadian rhythms, and confinement. Evidence from space missions and ground-based analogs demonstrates that microgravity significantly alters both innate and adaptive immunity, leading to impaired pathogen defense, heightened inflammatory responses, and reactivation of latent viruses.