Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease 
with selective loss of upper and lower motor neurons. At sites of motor neuron 
injury, neuroinflammation is a prominent pathological finding and is 
characterized by microglial activation, astrogliosis, and infiltration of 
monocytes and T-cells. Both innate and adaptive immune responses actively 
influence disease progression in animal models and in ALS patients, and promote 
neuroprotection or neurotoxicity at different stages of disease. The early 
immune reaction to signals from injured motor neurons is to rescue and repair 
damaged tissue. As disease accelerates, a shift occurs from beneficial immune 
responses (involving M2 microglia and regulatory T-cells) to deleterious immune 
responses (involving M1 microglia and Th1 cells). In this review, we underscore 
the importance of immune-mediated mechanisms in the pathogenesis of ALS and 
discuss the alterations and distinct phenotypes of immune cells at the different 
stages of disease. The better we understand the dynamic changes that occur 
within the immune system over the course of disease, the better we will be able 
to develop effective therapeutic regimens in ALS.