15.5 Short Answer: How can graft‑versus‑host disease (GVHD) be of benefit to patients with leukemia?
15.6 Multiple Choice: Which of the following options incorrectly describes a mechanism used to prevent fetal rejection?
A. High expression of 2,3‑dioxygenase (IDO), which starves T cells of tryptophan
B. Absence of MHC class II expression and low levels of MHC class I expression by the trophoblast
C. Downregulation of HLA‑G expression by the trophoblast
D. Secretion of TGF‑β and IL‑10 by the uterine epithelium and the trophoblast.
15.7 Multiple Choice: Which of the following is not a mechanism by which immunologically privileged sites maintain tolerance?
A. Exclusion of effector T cells during infection
B. Tissue barriers that exclude naive lymphocytes (for example, the blood–brain barrier)
C. Anti‑inflammatory cytokine production (for example, TGF‑β)
D. Expression of Fas ligand to induce apoptosis of Fas‑bearing effector lymphocytes
E. Decreased communication via conventional lymphatics 15.8 Multiple Choice: Which of the following is not a mechanism of peripheral tolerance?
A. Anergy
B. Negative selection
C. Induction of Tregs
D. Deletion
E. Suppression by Tregs 15.9 Short Answer: The phenomenon of epitope spreading occurs in systemic lupus erythematosus (SLE), where anti‑DNA autoantibodies are present and may progress to the production of anti‑histone antibodies. Describe mechanistically how this occurs.
15.10 Short Answer: Autoimmune polyendocrinopathy– candidiasis–ectodermal dysplasia (APECED) is caused by defects in the transcription factor AIRE, which result in impaired expression of peripheral genes and reduced negative selection (that is, impaired central tolerance). Patients afflicted with APECED suffer destruction of multiple endocrine tissues and exhibit impaired antifungal immunity. However, these autoimmune phenomena take time to develop and do not develop in all potential organ targets in all patients. Explain why this is the case.
15.11 Fill-in-the-Blanks: Autoantibodies that develop in certain autoimmune disorders can act as either antagonists or agonists, depending on whether they inhibit or stimulate a function. In _______________, autoantibodies against the _______________ receptor block its function in the neuromuscular junction, resulting in a syndrome of muscle weakness. Another example is _________________, where autoantibodies against the __________________ receptor stimulate excessive production of thyroid hormone.
15.12 Matching: Match the autoimmune disease with its pathophysiology:
A. Rheumatoid arthritis i. Chronic hepatitis C infection leading to    production of immune complexes that deposit in joints and tissues
Section references.
15-1 A critical function of the immune system is to discriminate self from nonself.
Ehrlich, P., and Morgenroth, J.: On haemolysins, in Himmelweit, F. (ed): The Collected Papers of Paul Ehrlich. London, Pergamon, 1957, 246–255.
Janeway, C.A., Jr: The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol. Today 1992, 13:11–16.
Matzinger, P.: The danger model: a renewed sense of self. Science 2002, 296:301–305.
15-2 Multiple tolerance mechanisms normally prevent autoimmunity.