464 PART I The Immune System in Health and Disease URE 20-1 Photomicrographs of (a)normal thyroid gland show- Hashimoto's thyroiditis showing intense lymphocyte infiltration / From follicle lined by cuboidal follicular epithelial cells and (b) gland in Web Path, courtesy of E. C Klatt, University of Utah from the small intestine. Binding of the auto-antibody to INSULIN-DEPENDENT DIABETES MELLITUS intrinsic factor blocks the intrinsic factor-mediated absorp- A disease afflicting 0.2% of the population, insulin-dependent tion of vitamin Biz. In the absence of suficient vitamin B12, diabetes mellitus (IDDM) is caused by an autoimmune which is necessary for proper hematopoiesis, the number of attack on the pancreas. The attack is directed against special- functional mature red blood cells decreases below normal. ized insulin-producing cells(beta cells)that are located in Pernicious anemia is treated with injections of vitamin B12, spherical clusters, called the islets of Langerhans, scattered thus circumventing the defect in its absorption An individual with autoimmune hemolytic anemia makes beta cells, resulting in decreased production of insulin and auto-antibody to RBC antigens, triggering complement consequently increased levels of blood glucose. Several factor mediated lysis or antibody-mediated opsonization and phago- are important in the destruction of beta cells. First, activated cytosis of the red blood cells. One form of autoimmune ane- CTLs migrate into an islet and begin to attack the insulin mia is drug-induced: when certain drugs such as penicillin or producing cells. Local cytokine production during this the anti-hypertensive agent methyldopa interact with red blood cells, the cells become antigenic. The immunodiag nostic test for autoimmune hemolytic anemias generally involves a Coombs test, in which the red cells are incubated with an anti-human igg antiserum. If IgG auto-antibodies are present on the red cells, the cells are agglutinated by the antiserum GOODPASTURE'S SYNDROME In Goodpasture's syndrome, auto-antibodies specific for certain basement-membrane antigens bind to the basement membranes of the kidney glomeruli and the alveoli of the lungs. Subsequent complement activation leads to direct cel lular damage and an ensuing inflammatory response medi ated by a buildup of complement split products. Damage to terular and alveolar basement membranes leads to progressive kidney damage and pulmonary hemorrhage Death may ensue within several months of the onset of symptoms. Biopsies from patients with Goodpasture's syn- FIGURE 20-2 Fluorescent anti-IgG staining of a kidney biopsy drome stained with fluorescent-labeled anti-IgG and anti- from a patient with Goodpasture's syndrome reveals linear deposits 3b reveal linear deposits of IgG and C3b along the base- of auto-antibody along the basement membrane. / From Web Path, ment membranes(Figure 20-2 courtesy of E. C. Klatt, University of Utah. jfrom the small intestine. Binding of the auto-antibody to intrinsic factor blocks the intrinsic factor–mediated absorp￾tion of vitamin B12. In the absence of sufficient vitamin B12, which is necessary for proper hematopoiesis, the number of functional mature red blood cells decreases below normal. Pernicious anemia is treated with injections of vitamin B12, thus circumventing the defect in its absorption. An individual with autoimmune hemolytic anemia makes auto-antibody to RBC antigens, triggering complement￾mediated lysis or antibody-mediated opsonization and phago￾cytosis of the red blood cells. One form of autoimmune ane￾mia is drug-induced: when certain drugs such as penicillin or the anti-hypertensive agent methyldopa interact with red blood cells, the cells become antigenic. The immunodiag￾nostic test for autoimmune hemolytic anemias generally involves a Coombs test, in which the red cells are incubated with an anti–human IgG antiserum. If IgG auto-antibodies are present on the red cells, the cells are agglutinated by the antiserum. GOODPASTURE’S SYNDROME In Goodpasture’s syndrome, auto-antibodies specific for certain basement-membrane antigens bind to the basement membranes of the kidney glomeruli and the alveoli of the lungs. Subsequent complement activation leads to direct cel￾lular damage and an ensuing inflammatory response medi￾ated by a buildup of complement split products. Damage to the glomerular and alveolar basement membranes leads to progressive kidney damage and pulmonary hemorrhage. Death may ensue within several months of the onset of symptoms. Biopsies from patients with Goodpasture’s syn￾drome stained with fluorescent-labeled anti-IgG and anti￾C3b reveal linear deposits of IgG and C3b along the base￾ment membranes (Figure 20-2). INSULIN-DEPENDENT DIABETES MELLITUS A disease afflicting 0.2% of the population, insulin-dependent diabetes mellitus (IDDM) is caused by an autoimmune attack on the pancreas. The attack is directed against special￾ized insulin-producing cells (beta cells) that are located in spherical clusters, called the islets of Langerhans, scattered throughout the pancreas. The autoimmune attack destroys beta cells, resulting in decreased production of insulin and consequently increased levels of blood glucose. Several factors are important in the destruction of beta cells. First, activated CTLs migrate into an islet and begin to attack the insulin￾producing cells. Local cytokine production during this 464 PART IV The Immune System in Health and Disease (a) (b) FIGURE 20-1 Photomicrographs of (a) normal thyroid gland show￾ing a follicle lined by cuboidal follicular epithelial cells and (b) gland in Hashimoto’s thyroiditis showing intense lymphocyte infiltration. [From Web Path, courtesy of E. C. Klatt, University of Utah.] FIGURE 20-2 Fluorescent anti-IgG staining of a kidney biopsy from a patient with Goodpasture’s syndrome reveals linear deposits of auto-antibody along the basement membrane. [From Web Path, courtesy of E. C. Klatt, University of Utah.]