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Chapter 3 : Molecular Mimicry and Central Nervous System Autoimmune Disease

Author: Robert S. Fujinami1
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Affiliations: 1: Department of Neurology, University of Utah School of Medicine, 30 N 1900 East, Room 3R330, Salt Lake City, UT 84132
Content Type: Monograph
Publication Year: 2000

Category: Microbial Genetics and Molecular Biology

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Abstract:

Infections have been associated with the initiation and/or exacerbation of multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). It is suspected that tolerance to self-CNS antigens is broken by several linked events. This results in the initiation or induction of anti-CNS immune responses, which lead to inflammation and demyelination. Myelin basic protein (MBP) is a major component of CNS myelin, and when it is emulsified in adjuvant it can be used to induce experimental allergic encephalomyelitis (EAE) when it is injected into animals. Researchers found that 8 of 17 patients had lymphocytes that proliferated in response to MBP, whereas 6 of 40 individuals with measles without encephalomyelitis had such lymphocytes. Recently, other researchers extended the concept of molecular mimicry and autoimmune CNS disease. They have elegantly shown that the cross-reacting epitope between virus microbe and self-CNS protein does not need to have identical amino acids in order for T-cell recognition to occur. Theiler's murine encephalomyelitis virus (TMEV) infection of mice leads to a chronic demyelinating disease that has similarities to the human demyelinating disease MS. Early after infection natural killer (NK) cells can kill infected cells as part of the innate immune response. Viruses can cause direct lysis of infected cells through either apoptotic or necrotic pathways. Once an antiviral immune response develops, antiviral antibodies can bind to the surfaces of infected cells, leading to the activation of the complement cascade that eventually kills the infected cell.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
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Molecular Mimicry and Central Nervous System Autoimmune Disease
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Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
/content/10.1128/9781555818074.chap3.fig3-1
Figure 1

Virus infection likely occurs in the periphery. Antigen-presenting cells (APCs) are infected and can present antigen in the MHC class I to CD8 T cells. In addition, antigen-presenting cells can ingest and process infected cell debris, leading to presentation of epitopes via class II and activation of CD4 T cells. Infected cells can be killed by several mechanisms. Virus can directly kill cells, leading to release of additional progeny virus. Activated NK cells can kill infected cells early after infection, leading to a reduction of virus progeny. As an immune response is mounted antibody and complement can kill infected cells. In many instances antibodies need to recognize the viral glycoproteins expressed on the surfaces of the infected cell. CD8 and, in some cases, CD4 T cells can lyse virus-infected cells through either perforin or Fas-mediated pathways. Ab, antibody; C, complement.

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10.1128/9781555818074/fig3-1.gif
Image of Figure 1
Figure 1

Virus infection likely occurs in the periphery. Antigen-presenting cells (APCs) are infected and can present antigen in the MHC class I to CD8 T cells. In addition, antigen-presenting cells can ingest and process infected cell debris, leading to presentation of epitopes via class II and activation of CD4 T cells. Infected cells can be killed by several mechanisms. Virus can directly kill cells, leading to release of additional progeny virus. Activated NK cells can kill infected cells early after infection, leading to a reduction of virus progeny. As an immune response is mounted antibody and complement can kill infected cells. In many instances antibodies need to recognize the viral glycoproteins expressed on the surfaces of the infected cell. CD8 and, in some cases, CD4 T cells can lyse virus-infected cells through either perforin or Fas-mediated pathways. Ab, antibody; C, complement.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
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Figure 2

Once CD4 or CD8 T cells are activated they can readily cross the blood-brain barrier. There these cells recognize common epitopes between virus and self-CNS antigens and release proinflammatory cytokines. Many of these are myelinotoxic and can kill the myelin-producing cell, the oligodendrocyte (OLIGO). In addition, macrophages (MAC) and plasma cells are drawn into the areas of inflammation. Plasma cells locally produce cross-reacting antibodies that bind to the myelin and/or myelin-supporting cells. Macrophages can recognize antibody produced by the plasma cells bound to myelin through Fc receptors. As myelin is eroded nerve conduction diminishes, leading to clinical signs of disease.

10.1128/9781555818074/fig3-2_thmb.gif
10.1128/9781555818074/fig3-2.gif
Image of Figure 2
Figure 2

Once CD4 or CD8 T cells are activated they can readily cross the blood-brain barrier. There these cells recognize common epitopes between virus and self-CNS antigens and release proinflammatory cytokines. Many of these are myelinotoxic and can kill the myelin-producing cell, the oligodendrocyte (OLIGO). In addition, macrophages (MAC) and plasma cells are drawn into the areas of inflammation. Plasma cells locally produce cross-reacting antibodies that bind to the myelin and/or myelin-supporting cells. Macrophages can recognize antibody produced by the plasma cells bound to myelin through Fc receptors. As myelin is eroded nerve conduction diminishes, leading to clinical signs of disease.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
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