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 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

Assumption of NO autoimmunity

- T cell unresponsiveness because of :

• Clonal deletion

• T-suppression

• Clonal anergy

• Inadequate anto-antigen presentation

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

Figure 17.1Possible mechanisms of induction of

autoimmunity.

Normal thyroid gland Gland in Hashimoto’s thyroiditis

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.]

Islet of Langerhans in pacreas from a normal mouse (a) and froma mouse with a disease resembling insulin-dependent diabetesmellitus (b)

“Butterfly” rash over the cheeks of a young girl with systemic lupus erythematosus

Rheumatoid arthirtis

Proposed mechanisms for induction of autoimmunity

• Release of sequestered antigens• Molecular mimicry• Inappropriate expression of class II MHC molecules• Polyclonal B cell activation

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