Multiple sclerosis and virus induced immune responses: Autoimmunity can be primed by molecular mimicry and augmented by bystander activation
Bibliographic record
Abstract
Polymicrobial infections have been associated with plausible immune mediated diseases, including multiple sclerosis (MS). Virus infection can prime autoimmune T cells specific for central nervous system (CNS) antigens, if virus has molecular mimicry with CNS proteins. On the other hand, infection of irrelevant viruses will induce two types of cytokine responses. Infection with a virus such as lymphocytic choriomeningitis virus (LCMV), can induce interferon (IFN)-alpha/beta production and suppress autoimmunity, while infection with a virus, such as murine cytomegalovirus (MCMV), can activate natural killer (NK), NKT and dendritic cells, resulting in interleukin (IL)-12 and IFN-gamma production. These cytokines can cause bystander activation of autoreactive T cells. We established an animal model, where mice infected with vaccinia virus encoding myelin protein can mount autoimmune responses. However, the mice develop clinical disease only after irrelevant immune activation either with complete Freund's adjuvant or MCMV infection. In this review, we propose that a combination of two mechanisms, molecular mimicry and bystander activation, induced by virus infection, can lead to CNS demyelinating diseases, including MS. Viral proteins having molecular mimicry with self-proteins in the CNS can prime genetically susceptible individuals. Once this priming has occurred, an immunologic challenge could result in disease through bystander activation by cytokines.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".