autoimmunity
DESCRIPTION
Autoimmunity. Autoimmunity. Loss of self tolerace leading to immune response to self tissues May be organ-specific, localized or systemic Genetic background plays a role in extent & severity of diseases. Virtually all autoimmune responses are T-dep. Formation of new or altered epitopes - PowerPoint PPT PresentationTRANSCRIPT
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Autoimmunity
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Autoimmunity
• Loss of self tolerace leading to immune response to self tissues
• May be organ-specific, localized or systemic• Genetic background plays a role in extent & severity of dis
eases.• Virtually all autoimmune responses are T-dep.• Formation of new or altered epitopes
– Sharing epitopes between tissues & agents (molecular mimicry)– Exposure of hidden antigens– Viral infections– Loss of control of lymphocyte responses
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Assumption of NO autoimmunity
- T cell unresponsiveness because of :
• Clonal deletion
• T-suppression
• Clonal anergy
• Inadequate anto-antigen presentation
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Criteria for autoimmune disease
• Direct proof – Transferring autoantibodies or self-reactive lymphocytes to h
ealthy individuals & reproduce the disease (for ethical reason, use scid mice)
• Indirect proof– Identify target antigen & reproduce the disease in the experi
mental animals– Study genetically predisposed animal models
• Circumstantial evidence– Familial tendency– Lymphocyte infiltration or MHC association– Clinical improvement with immune suppressive drugs
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Figure 17.1Possible mechanisms of induction of
autoimmunity.
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Normal thyroid gland Gland in Hashimoto’s thyroiditis
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Figure 17.2``Lumpy-bumpy'' staining pattern of fluorescent antibody specific for human Ig: immune aggregate deposits in glomerular basement membrane. [Courtesy of Dr. Angelo Ucci, Tufts University School of Medicine.]
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Islet of Langerhans in pacreas from a normal mouse (a) and froma mouse with a disease resembling insulin-dependent diabetesmellitus (b)
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“Butterfly” rash over the cheeks of a young girl with systemic lupus erythematosus
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Rheumatoid arthirtis
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Proposed mechanisms for induction of autoimmunity
• Release of sequestered antigens• Molecular mimicry• Inappropriate expression of class II MHC molecules• Polyclonal B cell activation
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Treatment of autoimmune diseases
• Current therapies– Immunosuppressive drugs– Removal of target tissues
• Experimental therapeutic approaches– T cell vaccination– Peptide blockade of MHC molecules– Monoclonal-antibody treatment– Tolerance induction by oral antigens