molecular mimicry

[Guest guest]

basicly, mold and possably bacterias, so closely related to our own cells, that

it's confuseing our body to where it not only attacks the invaders but our own

" SELF " causeing autoimmune disease.

but once again, the deturmination to put it all on self and not on environment

as the causeing factor. as always.

this is why I dont like genetics being brought into this.

science well forever ignore environmental toxin exposure if they can blame

genetics instead.

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molecular mimicry

describes the theory that microbial pathogens share pieces of antigenic

components with those of their hosts and when the host immune system attacks

these pathogens it does collateral damage to the host. Molecular mimicry is

thought to play an important role in triggering certain autoimmune diseases.

Paradoxically, infections are known to reduce the overall incidence of certain

allergies and autoimmune diseases.

http://www.discoverymedicine.com/-Yang/2009/07/25/editors-note-june-2005\

/

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MOLECULAR MIMICRY

http://en.wikipedia.org/wiki/Molecular_mimicry

HLA, molecular mimicry and multiple sclerosis.

Liblau R, Gautam AM.

Institut National de la Santé et de la Recherche Médicale, Pitie-Salpetriere

Hospital, Paris, France.

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central

nervous system in which an autoimmune response most probably contributes to

pathogenesis. To date, the best characterized susceptibility-associated gene has

been mapped to the HLA complex. The HLA-DRB1*1501 - DRB5*0101 - DQA1*0102 -

DQB1*0602 haplotype is both associated and linked to MS in different ethnic

groups. The locus within the HLA class II region encoding the MS-susceptibility

gene is under intensive investigation. Epidemiological studies, however, have

suggested that environmental antigens also play a critical role in MS

pathogenesis. One of the ways a pathogen could trigger autoimmune disease is via

immunological cross-reactivity or molecular mimicry. This concept argues that a

microbial peptide with certain degree of homology to a self peptide can

stimulate pathogenic self-reactive specific T cells to cause an autoimmune

disease. Many microbial agents have regions of sequences that may serve as

binding motifs for HLA-DR2. HLA genetics and molecular mimicry may therefore be

intimately interlinked in the disease process. In the present review, we focus

on the HLA association with MS and the role of microbial antigens in MS, with

special reference to the molecular mimicry hypothesis.

PMID: 11324698 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/11324698?dopt=Abstract

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Molecular Mimicry/MS

http://www.mult-sclerosis.org/MolecularMimicry.html

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J Immunol. 2009 Sep 1;183(5):3531-41. Epub 2009 Jul 31.

HLA-DQB1*0602 determines disease susceptibility in a new " humanized " multiple

sclerosis model in HLA-DR15 (DRB1*1501;DQB1*0602) transgenic mice.

Kaushansky N, Altmann DM, Ascough S, CS, Lassmann H, Ben-Nun A.

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

Abstract

The susceptibility to multiple sclerosis (MS), a chronic neurological autoimmune

disease that primarily targets CNS myelin, has long been associated with HLA

class-II genes. Although several other HLA and non-HLA disease predisposing

alleles have been identified, alleles of the HLA-DR15 haplotype (DRB1*1501,

DRB5*0101, and DQB1*0602) remain the strongest susceptibility factor. Many

studies have suggested that the HLA-DRB1*1501 allele determines MS-associated

susceptibility. However, due to strong linkage disequilibrium within the HLA

class II region, it has been difficult to unequivocally determine the relative

roles of the DRB1*1501 and DQB1*0602 products. In this study we use HLA class-II

transgenic mice to illuminate the relative contributions of the DRB1*1501 and

DQB1*0602 alleles or their combination to susceptibility toward a new

" humanized " MS-like disease induced by myelin-associated oligodendrocytic basic

protein (MOBP). Although many immunological studies have focused overwhelmingly

on the role of the HLA-DRB1*1501 product in MS, we show that HLA-DRB1*1501

transgenics are refractory to MOBP disease induction, whereas the HLA-DQB1*0602

transgenics are susceptible via T cells reactive against MOBP15-36 and MOBP55-77

encephalitogenic epitopes. Although both transgenics react against these

epitopes, the MOBP15-36- and MOBP55-77-reactive T cells are of Th2-type in

HLA-DRB1*1501 transgenics and are pathogenic Th1/Th17 cells in the HLA-DQB1*0602

transgenic mice. This new humanized model of MS further implicates autoimmunity

against MOBP in MS pathogenesis, provides the first evidence of pathogenic

HLA-DQ-associated anti-myelin autoimmunity, and is the first to offer a

rationale for HLA-DQB1*0602 association with MS. These findings have important

bearing on the candidacy of the DQB1*0602 allele as a genetic risk factor for

MS.

http://www.ncbi.nlm.nih.gov/pubmed/19648275

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Autoimmun Rev. 2010 Feb;9(4):233-6. Epub 2009 Aug 13.

The myelin-associated oligodendrocytic basic protein (MOBP) as a relevant

primary target autoantigen in multiple sclerosis.

Kaushansky N, Eisenstein M, Zilkha-Falb R, Ben-Nun A.

Department of Immunology, The Weizmann Institute of Science, P.O. Box 26,

Rehovot 76000, Israel.

Abstract

Multiple sclerosis (MS) is a disease of the human CNS, characterized by

perivascular inflammation, demyelination and axonal damage. Although the

etiology of MS is unknown, it is believed that the disease results from

destructive autoimmune mechanisms, presumably initiated by abnormal activation

of potentially pathogenic autoimmune T-cells recognizing CNS components. The

myelin-associated oligodendrocyte basic protein (MOBP), a relatively abundant

CNS-specific myelin protein, which plays a role in stabilizing the myelin sheath

in the CNS, has recently been implicated in the pathogenesis of MS. Here we

review studies showing that MOBP is as an important candidate target antigen in

MS as the other widely studied target antigens, myelin basic protein (MBP),

proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). The

studies summarized below indicate that T-cell autoimmunity against MOBP can be

detected in MS patients; T-cells reactive against MOBP can be pathogenic in

several mouse strains as well as in the " humanized " HLA-DR15-Tg mice; and, that

the HLA-DQ6-restricted, but not HLA-DR15-restricted, MOBP-reactive T-cells cause

in HLA-DR15-Tg mice MS-like clinical disease associated with perivascular and

parenchymal infiltration, demyelination, axonal loss, and optic neuritis.

Accordingly, the MOBP should be considered a bona fide primary target antigen in

MS, in addition to MBP, PLP, and MOG.

http://www.ncbi.nlm.nih.gov/pubmed/19683076

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J Autoimmun. 2001 May;16(3):293-302.

Structural basis of molecular mimicry.

Wucherpfennig KW.

Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA

02115, USA. wucherpf@...

Abstract

Infectious agents are thought to play an important role in the development of

autoimmune diseases. Sequence similarity between infectious agents and

self-proteins (molecular mimicry) has been proposed as a mechanism for the

induction of autoimmunity [1]. However, it has been difficult to identify

microbial peptides that activate autoreactive T cells using conventional

sequence alignments. This chapter reviews progress made in the identification of

such microbial peptides based on the analysis of structural features that are

important for TCR recognition of MHC-bound peptides [2].

http://www.ncbi.nlm.nih.gov/pubmed/11334495?dopt=Abstract