1. The Autoimmune insulin-dependent Diabetes mellitus: Major immunologic Features: 1- HLA-DR3 and DR4 haplotype expression on the beta cells of the islets of Langerhans. 2-Presence of reactive Autoantibodies directed against multiple antigens of islets beta cells. 3-Monocytic and lymphocytic infiltration of islets of Langerhans. 4-Some evidence for partial responses to immunosuppressive therapy.

2. Mechanism of Autoimmune destruction of islet beta cells: -Some types of infectious agents: Mumps virus, coxsackievirus types B3 and B4, Rubella virus, CMV, and some strains of influenza. -Expression of MHC class II on the surface of beta cells. -Presentation of Autoantigen ; Glutamic acid decarboxylase, and tyrosine phosphatase (IA-2). -APC (DC) interaction, migration, activation of helper cell.

3. -Specific T lymphocyte response; mainly CD8 cells, and some CD4 and NK cells inside the pancreatic islets. -Isotype switching of B lymphocytes. -Direct cytotoxicity to Beta cells; killing, release of Autoantigen. -FasL-mediated killing of beta cells.

4. Mechanism of Autoimmune destruction of beta cells:.

5. General Considerations: -Strong association (90%) with MHC class II haplotype DR3 and DR4 expression. -Seen almost in individuals under the age of 30 years. -It occurs predominantly in whites. -Prevalence rate in USA and Europe is 0.25%. -Males are more commonly affected than females. -No useful diagnostic procedure for autoimmune response before the appearance of IDDM.

6. Immunologic diagnosis and clinical features of IDDM: -Lymphocytic infiltration in the pancreatic islets. -Islets atrophy and glucose intolerance. -Immunofluorescence staining islet inflammation reveals: 1-Expression of HLA-DR on both beta cells and infiltrating lymphocytes. 2-CD8-Cytotoxic suppressor phenotype due to monoclonal antibodies staining. 3-Antibodies and complement present on beta cell surface.

7. -Auto-reactive antibodies localized in vitro: -Anti-Glutamic acid decarboxylase antibodies - Anti- tyrosine phosphatase antibodies. -Fasting blood glucose greater than 140mg/dl. -Other diagnostic tests: GTT, and HbA1c.

8. Adrenal Insufficiency: Addison’s Disease: Major Immunologic features: -Circulating antibodies against adrenal cells are present. -Complement is fixed on the surface of adrenal cells. -It is associated with other autoimmune diseases. Mechanism of adrenal cell destruction: -Expression of Auto-antigen 21-hydroxylase enzyme by MHC class II on the surface of cell. - Specific APC interaction.

9. -Migration of APC to the lymph nodes. -Activation of specific T helper cells. -Monoclonal B lymphocyte isotype switching. -Production of Auto-reactive antibodies. -Attachment to cortical cell surface. -Complement fixation, cellular destruction.

10. General Considerations: -Addison’s disease is the most common form of adrenal insufficiency, accounting for 70-80% of all cases. -The prevalence is relatively low. -Affect young individuals (30-40 years’ old). -Female to male ratio is 1.8:1. -Seen most commonly as part of polyglandular syndrome ( 40% of autoimmune adrenal insufficiency). -Strong association with HLA-DR3,4 for other 60% of cases.

11. Immunologic diagnosis and clinical features: -Microscopy: lymphocytic infiltration. -Immunofluorescence (direct) staining shows: 1-Autoantibodies on the surface of cortical cells. 2-Complement fragments. -Serum levels of adrenocorticotropic hormone (ACTH) are elevated. -Decreased serum Cortisol level. -Serology: Detection of serum anti-adrenal cortical cells antibodies in up to 80% of cases by Indirect immunofluorescent.

12. Autoimmune polyglandular syndromes: Major immunologic features: -Circulating antibodies against multiple endocrine organs. -HLA-DR expression on affected cells. Type I syndrome: -It occurs in childhood before 10 years. -Oral Candidiasis and hypoparathyroidism (70% of cases). -40-70 % of patients go on to develop adrenal insufficiency. -Minor association with Gonadal failure.

13. N Type II syndrome: -It occurs mainly between the ages of 20-30 years. -Has a 2:1 female predominance. -familial inheritance of mutant allele. -HLA-DR3 association. -Major criteria: Adrenal failure, Thyroid disease, and IDDM. -Minor: Gonadal failure. Type III syndrome: -Autoimmune thyroid disease associated with IDDM or Autoimmune Anti-intrinsic factor Abs (gastric disease).