The Peripheral Neuropathy Solution

The Peripheral Neuropathy Solution

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" From P. R Carnegie and M A Lawson, loday's hfe Sri 3(2), 14 (1991) h Single letter amino acid code ' P2, Protein of peripheral nerves

" From P. R Carnegie and M A Lawson, loday's hfe Sri 3(2), 14 (1991) h Single letter amino acid code ' P2, Protein of peripheral nerves

Table 9-2

Potential Mechanisms of Induction of Autoimmune Disease hv Viruses

Molecular numiciy vual protein elicits bumoial and/or cellular immune response cross-

reacting with identical oi similar epitope fortuitously present on a cellular protein Polyclonal B-cell activation B lymphocytes transformed hy certain viruses (e g , Epstein-Darr virus) secrete antibodies against a wide range of antigens, including normal cell proteins Cytokine induction of MUC antigens, vims induces production of interferon y and tumor necrosis factor, which induce expression of MHC class II protein on brain cells that do not usually express it (e g , glial cells), enabling them to present antigens such as myelin to T cells

Exposure ot sequestered cellular protein incorporation into viral envelope or release from virus-infected cell (in altered or precursor form7) T-cell dyslunclion- viral destruction or down-regulation of T cells that normally suppress immune response to self proteins the P2 protein of peripheral nerve myelin will cause the experimental equivalent of Guillain-Barre syndrome. There is mimicry between this epitope and a sequence in the influenza virus NS2 protein. Ordinarily, this nonstructural protein is removed from influenz.a virus vaccine during its purification; failure to do this in some batches of swine influenza vaccine used in the crisis program mounted in the United States in 1976-1977 may account for the apparent increase in incidence of the Guillain-Barre syndrome at that time.

A feature of the postinfectious encephalomyelitis that follows a few weeks after about 1 in every 1000 cases of measles (and somewhat less frequently following varicella, mumps, rubella, or vaccinia) is that the virus can rarely be isolated from the brain; however, MBP can be found in the cerebrospinal fluid, and, at least in the case ol measles, anti-MBP antibodies and T cells are detectable in the blood. Theoretically, autoimmune damage can continue long after the virus that triggered it has been cleared from the body. Once the cross-reactive viral amino acid sequence has induced a humoral and/or cellular immune response that brings about lysis of normal tissue, cellular protein that is normally sequestered will be released. Providing that the cellular protein is capable of immune recognition by the host, this may precipitate a chain reaction. Implicit in the hypothesis that molecular mimicry is responsible for viral induction of autoimmune disease is the notion that immunologic tolerance has somehow been broken, because the viral epitope has been seen as foreign and has elicited an immune response capable of cross-reacting with a host protein.

Humans suffer from numerous autoimmune diseases, ranging from multiple sclerosis to rheumatoid arthritis. All are incurable, many are common, and most are of unknown etiology. Viruses are a major suspect as triggers for these diseases; however, definitive proof has yet to be produced, and this problem continues to be an important area for research. Current theories for which there is some evidence are summarized in Table 9-2.

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