Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)is a rare disease in which there is autoimmune destruction of several endocrine organs.This disease is caused by mutations in the autoimmune regulator gene called AIRE.AIRE is normally expressed primarily in the thymus and serves as a transcription factor in thymic epithelial cells.A failure to produce AIRE leads to a failure in tolerance to several self-proteins.Which ONE of the following statements best explains the influence of AIRE on self tolerance?
A)AIRE up-regulates expression of proteins that induce proliferation of thymic epithelial cells,allowing greater self antigen presentation to T cells.
B)AIRE up-regulates expression of cytokines that inhibit activation of T cells.
C)AIRE up-regulates expression of MHC proteins,allowing for greater self antigen presentation to developing T cells.
D)AIRE up-regulates expression of proteins usually expressed only in peripheral organs,allowing presentation of the proteins to developing T cells.
E)AIRE up-regulates expression of Fas ligand on thymic epithelial cells to induce apoptosis in self-reactive T cells.

Question

Quizplus · Accepted Answer

In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED),there is an autoimmune attack of specific peripheral organs such as the pancreas,adrenals,and thyroid gland.Because the mutation occurs in a protein primarily expressed in the thymus,the underlying pathophysiology of the disease most likely represents a breakdown in central tolerance.Self-reactive T cells that are negatively selected in normal individuals instead survive in patients with autoimmune regulator gene (AIRE)mutations.Because specific organs are always involved in the disease,this is not just a general reduction in antigen presentation to developing T cells.AIRE functions to up-regulate intrathymic expression of certain proteins expressed in peripheral organs,so that these peptides can be presented to developing T cells.In this way,T cells specific for these peripheral self peptides can be deleted.Inhibitory cytokines play a role in tolerance mainly in the periphery.Fas ligand is not involved in the negative selection of T cells in the thymus,but it does play a role in peripheral T cell tolerance.

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED)is a Rare Disease in Which There