Fig. 15.11 Identification of autoantibodies that can transfer disease in patients with myasthenia gravis. Autoantibodies from the serum of patients with myasthenia gravis immunoprecipitate the acetylcholine receptor from lysates of skeletal muscle cells (right‑hand panels). Because the antibodies can bind to both the murine and the human acetylcholine receptor, they can transfer disease when injected into mice (bottom panel). This experiment demonstrates that the antibodies are pathogenic. However, to be able to produce antibodies, the same patients should also have CD4 T cells that respond to a peptide derived from the acetylcholine receptor. To detect them, T cells from patients with myasthenia gravis are isolated and grown in the presence of the acetylcholine receptor plus antigen‑presenting cells of the correct MHC type (left‑hand panels). T cells specific for epitopes of the acetylcholine receptor are stimulated to proliferate and can thus be detected.
Disease can be transmitted by transfer of T cells from affected animal Mice injected with myelin basic protein and complete Freund's adjuvant develop EAE and are paralyzed The disease is mediated by TH17 and TH1 cells specifc for myelin basic protein TNF-˜IFN-°paralysisparalysisMouse after induction of EAE (left), compared with normal healthy mouse IL-17TH17TH1
Fig. 15.12 T cells specific for myelin basic protein mediate can also cause these disease symptoms. Inflammation of the brain inflammation of the brain in experimental autoimmune and paralysis are mediated by TH1 and TH17 cells specific for MBP. encephalomyelitis (EAE). This disease is produced in experimental Cloned MBP‑specific TH1 cells can transfer symptoms of EAE to animals by injecting them with isolated spinal cord homogenized in naive recipients provided that the recipients carry the correct MHC complete Freund’s adjuvant. EAE is due to an inflammatory reaction allele. In this system it has therefore proved possible to identify the in the brain that causes a progressive paralysis affecting first the tail peptide:MHC complex recognized by the TH1 clones that transfer and hind limbs (as shown in the mouse on the left of the photograph, disease. Other purified components of the myelin sheath can also compared with a healthy mouse on the right) before progressing induce the symptoms of EAE, so there is more than one autoantigen to forelimb paralysis and eventual death. One of the autoantigens in this disease. Photograph from Wraith, D., et al.: Cell 1989, identified in the spinal cord homogenate is myelin basic protein 59:247–255. With permission from Elsevier. (MBP). Immunization with MBP alone in complete Freund’s adjuvant
Pregnancy can demonstrate a role for antibodies in disease, as IgG antibodies, but not T cells, can cross the placenta (see Section 10-15). For some autoimmune diseases (Fig. 15.13), transmission of autoantibodies across the placenta leads to disease in the fetus or neonate (Fig. 15.14). This provides proof in humans that autoantibodies cause some of the symptoms of autoimmunity. The symptoms of disease in the newborn infant typically disappear rapidly as