When Mandy's mom brought her in for her one-year checkup, the first thing her pediatrician noticed was her rash. Mandy had had dry itchy skin when she was seen for her first DPT vaccination at two months, and it had worsened during her first year of life. She had had an allergic reaction to cow's milk and to soy milk. Now she had open lesions that were oozing clear fluid. Her mom was trying to hold Mandy's hands so she wouldn't scratch her skin.
Mandy's temperature and vital signs were was normal. She was somewhat small for her age. She had infected pustules on her face, trunk, scalp, arms, and legs. In the folds of her elbows and knees, the skin was thickened. The physician took a culture from the skin and had her admitted to the hospital, where she began intravenous antibiotics and topical steroids and skin moisturizing lotions. He also requested a consult with an allergist to find the cause of Mandy's rash.
The skin cultures were positive for Staphylococcus aureus and Streptococcus pyogenes Group A. Mandy's WBC counts was 9,600/ml, with 41% PMNs, 26% lymphocytes, and 25% eosinophils (normal = 0-5%). The absolute eosinophil count was 2,400/ml (normal 0-500), and her serum IgE was 32,000 IU/ml (normal 0-200). A skin biopsy (a. left panel below) showed that Mandy's skin was positive by immunostaining for cathepsin G inflammatory cells; a normal skin biopsy is shown in b.
Mandy showed a positive skin test for numerous food and inhaled antigens, including dust mites, mold spores, animal dander, pollens, milk, egg white, soy, and peanuts. Her mother suffers from hay fever, and her father has atopic dermatitis. The family lives in an old house with carpeting in every room; they also have a cat. Neither parent smokes. Mandy developed hives and eczema after being fed a challenge dose of powdered milk, and her serum tryptase levels increased, a sign of IgE-mediated mast cell degranulation.
Mandy was diagnosed with atopic dermatitis (AD), an allergic skin reaction to inhaled and ingested allergens. Allergens are small protein molecules that easily cross mucous membranes and can travel through the blood to the skin. As many as 10% of children have AD, and up to 80% of those children have defective cell-mediated immunity.
Cytokines released by allergen contact or by scratching stimulate skin keratinocytes (epidermal cells) to release IL-1, IL-6, IL-8, GM-CSF, and TNF-alpha. In response to these cytokines, dermal fibroblasts secrete chemokines that attract macrophages and T cells. IL-1 and TNF-alpha induce vascular endothelial cells to express E-selectin, ICAM-1, and VCAM-1. Th2 cells found in acute skin lesions secrete IL-4, IL-5, IL-6, IL-10, IL-13, GM-CSF, eotaxin, and RANTES. IL-4 activates keratinocytes and fibroblasts to secrete IL-8 and MCP-1 and IL-1, which attract and activate T cells, and MCP-3 and MCP-4, which attract eosinophils.
Langerhan's cells and macrophages that infiltrate the AD lesions have IgE bound to CD23, a low-affinity IgE receptor. They can act as antigen-presenting cells and activate naïve T cells. Mast cells in the tissues bind IgE via the high-affinity FceRI.
Mandy's parents were advised to cover her mattress and pillow with plastic to minimize contact with dust and dust mite allergens, and to remove the carpeting and find another home for the cat. Mandy was put on a diet that excluded milk, egg white, soy, and peanuts. Once her infections were cured, she was treated with low-dose topical steroids and skin moisturizers and was dressed in cotton clothes. Perfume-free soaps were used in the household and the laundry was double-rinsed to avoid skin irritation. Mandy's rash improved, with occasional outbreaks usually associated with food allergen exposure. Antihistamines were used to control the itching. If the skin is not scratched, no rash occurs.
When she was five years old, Mandy developed itchy vesicles that spread and became very painful open sores. Her pediatrician diagnosed Herpes Simplex I and prescribed acyclovir, which cleared up the lesions. She developed thrush (Candida albicans infection) when she was 9; it responded to anti-fungal medications.
1. What is a hypersensitivity? How does it different from a normal immune response to a pathogen?
2. Describe the mechanism for Type I hypersensitivity. What T cells are involved in this reaction?
3. What are the roles of chemokines, cytokines, and adhesion molecules in AD?
4. How does the presence of IgE on Langerhan's cells and macrophages increase their effectiveness as antigen-presenting cells?
5. How is the skin test for allergens different from the skin test for TB exposure? [In both tests, a small amount of antigen is injected into the skin.] What is immuostaining?
6. Steroid creams were effective at reducing Mandy's rash; why? [Hint: see Parham Chapter 12] How does scratching cause the rash?
7. Why did Mandy develop an extensive herpes infection and thrush? Which immune mediators are deficient and why?
8. Skin infections with Staph and other bacteria make AD worse. Explain why. [Hint: review Exam 2.]
Answer the questions with as much detail as possible and save as a Word document entitled YourNameCase8.doc. Send to jdecker@u.arizona.edu as an attachment by 9 AM Tuesday July 1. Make sure your name is in the document as well as in the title.
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