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KEY CONCEPTS

KEY CONCEPTS

  • Immune mechanisms, both intrinsic to the brain and spinal cord as well as extrinsically derived from the peripheral immune system, are important in fighting central nervous system infections and mediating repair after injury.

  • There are two main components of the immune system. The innate immune system and the adaptive immune system.

  • The innate immune system is older from an evolutionary perspective and represents the first line of defense. It recognizes and responds to conserved patterns associated with certain pathogens and tissue injury.

  • The adaptive immune system mounts a targeted immune response against specific antigens and includes two components, humoral immunity (mediated by antibody production by B lymphocytes) and cell–based immunity (mediated by T lymphocytes).

  • Such immune responses can damage the nervous system through numerous mechanisms and contribute to a range of disorders through processes referred to as neuroinflammation.

  • Autoimmune diseases are a prominent example of mistargeted immune responses that are directed against “self antigens.” These diseases involve the production of “autoantibodies” by B cells and the actions of T cells against self antigens.

  • Many systemic autoimmune disorders can affect the nervous system. Additionally, several autoimmune disorders, such as multiple sclerosis (MS) and myasthenia gravis, selectively target the nervous system.

  • MS occurs primarily via cell–mediated destruction of myelin sheaths and consequent damage to underlying axons.

  • Myasthenia gravis and the related Lambert–Eaton syndrome occur primarily via antibody–mediated destruction of the neuromuscular junction.

  • Management of autoimmune disorders involves both acute treatments to suppress an active immune response and chronic therapies to prevent disease relapse and progression.

  • Acute treatments include corticosteroids, plasma exchange, and in some cases intravenous immunoglobulin, which broadly and nonspecifically dampen the activity of immune cells and circulating proinflammatory factors.

  • Chronic maintenance therapies either modulate specific components of the immune system or suppress the immune system more generally.

  • Additionally, myasthenia gravis is treated with agents that promote the function of acetylcholine, the neurotransmitter at the neuromuscular junction.

Under normal conditions the central nervous system (CNS) is immunologically privileged, meaning that immune cells from the periphery cannot penetrate the brain and spinal cord due to the blood–brain barrier (Chapter 2). Nevertheless, immune activation and associated inflammatory responses—generated both by the CNS’s resident immune system and by the recruitment of peripheral immune mechanisms—are important in protecting the CNS from acute infections and in regulating tissue recovery after injuries. By contrast, aberrant or chronic inflammatory responses can be neurotoxic and contribute to numerous and diverse disease states. Immune–mediated damage to the nervous system can present in disparate ways, typically with a clinical presentation consisting of specific functional impairments corresponding to the site of neural injury. For example, immune damage to the corticospinal tracts in the brain or in the spinal cord affects primarily motor function, while excessive immune activation in the forebrain can cause selective cognitive or emotional abnormalities. Systemic autoimmune conditions, such as lupus erythematosus, can affect the CNS and their initial presentation frequently involves neurologic ...

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