GENERAL CONCEPTS. Immune system distinguishes between self (auto) and non-self (foreign) antigens V genes encode TCR’s and BCR’s with anti-self reactivity Autoreactive T and B cells are produced If mature autoreactive T and B cells are activated, autoimmune disease may develop
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If helper T cell is tolerant,
B cell will not respond.
Without T cell help, B cell
Peripheral tolerance mechanism
T cells die during an immune response
Avidity Model vs.
Differential Signaling Model
Apoptosis is mediated
by Fas pathway.
Defect causes fatal
CTLA-4 required for function of Treg cells
Mutations in FoxP3 cause fatal multi-organ autoimmune disease in humans
as partial agonist
Impairs primary signal through TCR
Naive T cells interact with professional antigen-presenting cells for a primary response.
Other cell types lack MHC class II and co-stimulatory molecules and cause anergy.
risk for certain autoimmune
diseases in humans
1. Administer intact mouse cytochrome c to mouse and nothing happens.
2. Administer peptide of mouse cytochrome c, and autoimmune disease develops.
Enbrel is FDA-approved
Orencia is FDA-approved for rheumatoid arthritis
Clinical trials with non-Hodgkin’s lymphoma, and colon & ovarian cancer patients
Ipilimumab to treat melanoma, prostate & lung cancer - FDA application pending
Clinical trials with melanoma, renal cell carcinoma, and glioblastoma patients