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KEY CONCEPTS

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  • Immune mechanisms, both intrinsic to the brain and spinal cord and derived from the periphery, 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 is the first line of defense and responds to conserved components of microbes and evidence of tissue injury.

  • The adaptive immune system mounts immune responses against specific microbes, which includes 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 many mechanisms and contribute to a range of disorders through processes referred to as neuroinflammation.

  • Autoimmune diseases are a prominent example of immune-mediated damage of the nervous system, which is mediated by antibodies or T cells reacting 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.

  • Treatments for these autoimmune disorders are based largely on targeting specific components of the immune system or the use of general immunosuppressive agents.

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

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INTRODUCTION

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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 1). Nevertheless, immune mechanisms and the inflammatory responses they mediate—generated both by the CNS’s resident immune system and by the recruitment of peripheral immune mechanisms—are important in helping the CNS recover from acute infection or injury. By contrast, chronic autoimmune and inflammatory responses contribute importantly to numerous disease states. Immune-mediated damage to the nervous system can present in diverse ways, reflecting injury to specific neural substrates. In some instances immune damage affects primarily motor function but in other situations can cause selective behavioral abnormalities. Several common systemic autoimmune conditions, such as lupus erythematosus, affect the CNS and indeed often present initially with neurologic and psychiatric symptoms. Certain autoimmune disorders target the CNS selectively; examples include multiple sclerosis (MS) and other demyelinating illnesses (eg, neuromyelitis optica or Devic syndrome), paraneoplastic forms of encephalitis, stiff person syndrome (caused by autoantibodies directed against glutamic acid decarboxylase; Chapter 5), and myasthenia gravis and related conditions (eg, Lambert–Eaton syndrome). Chronic neuroinflammation also plays an important role in several disorders not classically considered neuroimmune, such as neuropathic pain (Chapter 11), Alzheimer disease and Parkinson disease (Chapter 18), and stroke (Chapter 20). Finally, inflammatory processes have been implicated, albeit more speculatively, in several psychiatric disorders as well as in normal aging...

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