At 42 years old, Stephanie Goldstein developed occasional blurred and double vision, numbness and “pins and needles” in her arms and legs (paresthesia), and bladder incontinence. After a month of these symptoms she went to her doctor, who sent her to the neurology specialist. An MRI scan revealed areas of demyelination in the central nervous system (CNS) and Stephanie was diagnosed with the autoimmune disease multiple sclerosis (MS). Which of the following best explains why some people are susceptible to the development of MS?
a. Negative selection of autoreactive T cells occurs during T-cell development.
b. Apoptosis of autoreactive B cells occurs in the bone marrow during B-cell development.
c. An inability to produce immunological tolerance toward CNS-derived constituents results in the generation of self-reactive lymphocytes.
d. An immunodeficiency inhibiting somatic recombination of immunoglobulins and T-cell receptors results in impaired lymphocyte development.
e. Regulatory T cells fail to activate autoreactive T cells in secondary lymphoid organs.
Rationale: The correct answer is c. One mechanism for achieving immunological tolerance to self proteins is negative selection in the thymus. Developing T cells bearing T-cell receptors that bind too strongly to self-MHC or to self-MHC:self-peptide complexes are signaled to die by apoptosis, which eliminates self-reactive T cells. Self proteins not presented to developing T cells in the thymus, such as proteins sequestered in the central nervous system, would not be scrutinized during negative selection, and self-reactive T cells would result.