Pancreas autoimmune response

The pathogenesis of type I diabetes is autoimmune destruction of the cells of the pancreas. The factor or factors that trigger this autoimmune response are unknown. Predisposing factors appear to include certain major histocompatibility complex haplotypes and autoantibodies to various islet cell antigens. The progression of the autoimmune response is characterized by lymphocytic infiltration and destruction of the pancreatic cells resulting in insulin deficiency. Type I diabetes mellitus constitutes about 10% of cases of diabetes mellitus. 

The current concept of autoimmune diabetes is that pancreas islet P cells are destroyed by an autoimmune response mediated by T lymphocytes that react specifically to one or more P cell proteins (Bach, 1994). Figure 25.1 shows the pathogenesis of type 1 diabetes. This concept gave rise to the idea that auto-immune diabetes can be prevented by the manipulation of autoreactive T cells or... 

Type 1 diabetes affects approximately 1 in 200 Americans, with a sibling recurrence risk of about 6%. It is an example of an autoimmune disease (see Immunology Lecture Notes), in which self-reactive T cells infiltrate the pancreas to destroy insulin-produdng islet cells. Mutations in the class II major histocompatibility locus (MHC) region are estimated to contribute about one third of the risk of developing type 1 diabetes. Mutations in or near the insulin gene itself are responsible for another 10-15% of the risk. 

TGF-/31 was also evaluated with NOD mice for the prevention of autoimmune diabetes, since it down-regulates many immune responses (Piccirillo et al., 1998). In TGF-/31 expression plasmid, pCMV-TGF-/ 1, the mTGF-/31 cDNA is under the transcriptional control of a CMV promoter/enhancer. Intramuscular injection of the plasmid showed TGF-/51 mRNA expression in skeletal muscle cells, as well as an increased level of TGF-/31 in the plasma of treated mice. Administration of pCMV-TGF-gl / was effective in protecting NOD mice from insulitis and diabetes. In addition, there was a decreased expression of IL-12 and IFN7 mRNA in the pancreas of protected mice. 

Figure 33-44 Consequences of autoimmunity. Photomicrographs of an islet of Langerhans (A) in the pancreas of a normal mouse and (B) in the pancreas of a mouse with an immune response against pancreatic (3 cells, which results in a disease resembling insulin-dependent diabetes mellitus in human beings. [From M. A. Atkinson and N. K. Maclaren. What causes diabetes Copyright 1990 by Scientific American. Inc. All rights reserved.]...

Autoimmune disorders are characterized by the breakdown of various connective tissues (the collagen diseeises), such as lupus erythematosus, polyarteritis nodosa, rheumatoid arthritis, and rheumatic fever. Also, it is suspected that autoimmune reactions may be responsible in part for certain abnormalities associated with (1) diabetes, when there heis been an unexplainable deterioration of the cells of the pancreas that secrete insulin (2) insufficient secretion of adrenal cortical hormones (Addison s diseeise) due to weisting of the glandular tissue (3) lack of stomach acid (achlorhydria) and/or lack of intrinsic factor resulting in pernicious anemia, because antibodies have attacked the cells of the stomach which secrete the deficient substances and (4) ulcerative colitis, when the lesions are much more severe than might be expected under the circumstances. 

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