A 28-year-old man comes to the emergency department after sustaining an accidental penetrating injury to the left eye. Examination shows left globe perforation with decreased visual acuity. The right eye is normal. The patient is otherwise healthy. Surgical treatment is performed with subsequent improvement in vision. Two months later, the patient experiences pain, photophobia, and diminished vision in the right eye. Evaluation shows leukocytes in the anterior chamber and vitreous humor and choroidal deposits consistent with granulomatous panuveitis. Disruption of which of the following immune processes is most likely responsible for this patient's current condition?

Question

A 28-year-old man comes to the emergency department after sustaining an accidental penetrating injury to the left eye.  Examination shows left globe perforation with decreased visual acuity.  The right eye is normal.  The patient is otherwise healthy.  Surgical treatment is performed with subsequent improvement in vision.  Two months later, the patient experiences pain, photophobia, and diminished vision in the right eye.  Evaluation shows leukocytes in the anterior chamber and vitreous humor and choroidal deposits consistent with granulomatous panuveitis.  Disruption of which of the following immune processes is most likely responsible for this patient's current condition?

Quizplus · Accepted Answer

This patient with a traumatic ocular injury has developed granulomatous inflammation of the contralateral eye, a condition known as sympathetic ophthalmia. This occurs when there is a robust T-cell response to previously sequestered antigens in the eye, an area that displays immune privilege. Certain anatomic sites (eg, eyes, testes) have inherent immune privilege, in which inflammation is inhibited by multiple mechanisms (eg, physical barriers, lack of lymphatics, low expression of MHC class Ia); this helps limit potential organ damage that may result from a robust inflammatory response. Self-antigens located in immune-privileged sites can be recognized by T cells that escape negative selection in the thymus. Therefore, if these self-antigens are released into the lymphatic system as a result of trauma, T cells may recognize these self-antigens as foreign and mount a response in both the injured eye and the contralateral eye. Bacterial introduction and exposure during trauma may upregulate the inflammatory process, increasing the chances that these autoreactive T cells will develop. Because of this potential sight-threatening immune response, if an eye is severely injured with no possibility that vision will be restored, it is enucleated (ie, surgically removed) to prevent blindness in the uninjured eye. (Choice A) Disorders of complement regulation can lead to autoimmune disease (eg, paroxysmal nocturnal hemoglobinuria) or increased susceptibility to infections with encapsulated bacteria (eg, Neisseria), but these disorders are typically genetic conditions rather than the result of trauma. (Choice C) Immune surveillance is a process by which cytotoxic lymphocytes and natural killer cells can recognize neoplastic cells either by their expression of tumor antigens or by a lack of expression of self-antigens (eg, MHC class I). (Choice D) Immunoglobulin class switching is the process through which activated B lymphocytes switch production from IgM immunoglobulins during the primary immune response to IgG and IgA isotypes, which are active during the secondary response. This occurs in the germinal centers of lymph nodes and requires interaction of the CD40 receptor on B cells with the CD40 ligand expressed by activated T cells. (Choice E) Positive selection of T cells occurs prior to negative selection and is responsible for development of a T cell repertoire that can recognize and bind to self-MHC molecules. T cells expressing a T-cell receptor that is able to bind self-MHC are allowed to survive (although if that response is too strong, they will usually be eliminated through negative selection). Educational objective: Traumatic injury to the eye, an area of the body that has inherent immune privilege, can lead to the release of previously sequestered antigens that T cells recognize as foreign. This can lead to subsequent inflammation and blindness in both the injured and uninjured eye.

A 28-Year-Old Man Comes to the Emergency Department After Sustaining