12 msfocusmagazine.org Health & Wellness Relapse and the Immune System: What’s Really Going on? By Ben Thrower, M.D. “Relapse” is an important concept to understand in multiple sclerosis. Most people know the basics: A relapse (also known as an exacerbation or attack) is defined as a new or worsened neurological symptom(s) persisting forat least 24 hourswith no betterexplanation. When diagnosed, 85 percent of people with multiple sclerosis will have a relapsing- remitting form of the disease. With each MS relapse, there is always the potential that the person does not return to their previous baseline and therefore, a new level of disability. One of the goals of treating multiple sclerosis with any of the available disease-modifyingtherapies is the prevention of relapses. What is actually going on, however, during an MS relapse in terms of the immune system? The human immune system is incredibly complex. It is made up of both cells and chemical messengers (cytokines) that allow for communication between immune cells. When working appropriately, the immune system is highly regulated and has a balance between inflammatoryand anti-inflammatory actions. The human central nervous system is selective about what immune cells can traffic in an area. The blood-brain barrier helps protect the human brain from potentially damaging inflammatory cells, chemicals, and other substances. During an MS relapse, inflammatory cells from the human immune system cross the blood-brain barrier into the brain and spinal cord, resulting in damage to myelin and nerve fibers (axons). It’s thought that cells in the central nervous system, called glia, become activated and secrete cytokines thatserveassortofahoming signal forinflammatorycells. The blood-brain barrier is less effective in the person with multiple sclerosis at keeping these inflammatory cells out. What we don’t know at this point is what turns on these glial cells in the first place. Some of the cells involved in the immune attack of a relapse include T-cells, B-cells and macrophages. T-cells can be further divided into classes called CD4 and CD8 cells. CD4 cells can be further divided into cells called Th1, Th17 and Th2. The Th1 and Th17 cells are felt to be inflammatory in nature and are relatively overrepresented in peoplewith MS. During a relapse,Th1 andTh17 cells may be moving across the blood-brain barrier more easily, resulting in myelin/axon During an MS relapse, inflammatory cells from the human immune system cross the blood-brain barrier into the brain and spinal cord, resulting in damage to myelin and nerve fibers