Case 8

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 18/02/2015

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CASE 8

TC is a 9-year-old child with recurrent necrotic infections on the legs and arms. Discussion with the parents to determine anomalies since birth revealed that TC’s umbilical cord had persisted much longer than that of his siblings. As well, TC’s wounds healed more slowly and left noticeable scars. Both parents emphasized that they were well and that no members of the extended family had presented with similar history. Swabs reveal repeated bacterial infections. A complete blood cell count with differential showed a normal number of leukocytes, although the numbers were slightly elevated. Serology showed no deficit in immunoglobulins, complement, or numbers and function of B and T cells. B cell function was based on antibody titers to childhood immunization, whereas T cell function was based on cytokine secretion by polyclonally stimulated T cells. What might be going on, and what would you do about it?

QUESTIONS FOR GROUP DISCUSSION

1. TC has had repeated bacterial infections. What immunologic cells or factors function to destroy this type of infection?

2. It is not surprising that TC’s leukocyte count is slightly elevated because he has an infection. Yet, laboratory investigations revealed no defects in B cell or phagocyte number or function. Additionally, the CH50 and AP50 tests for complement were normal. How would you proceed?

3. Given the laboratory tests and the fact that the infections are localized (not systemic or multi-site), review briefly some of the immunodeficiency disorders that can be ruled out.

4. What tests could you perform to rule out defects in the phagocytic function (see Case 6) or defects in toll-like receptors (see Case 7)?

5. What is the significance of necrotic rather than pustular manifestations of infection?

6. If one of the primary components of pus is dead neutrophils, what does the presence of necrotic rather than pustular infections suggest? (Hint: neutrophils are circulating cells and are not normally found in tissues.)

7. Review the processes involved in getting leukocytes from the circulation to the site of infection? Include in your answer each of the following (a) selectins, (b) integrins and their counter molecules on the endothelium, (c) PECAM, (d) chemokines, (e) matrix metalloproteinases, and (f) transmigration/diapedesis.

8. Activated tissue macrophages secrete the cytokines interleukin-1 and tumor necrosis factor. What role do these cytokines play in the inflammatory response?

9. The β2 integrins are heterodimers that play an important role in the firm adhesion of circulating leukocytes to the vascular endothelium. What is the common chain of these β2 integrins? Name two of the best characterized members of the β2 integrin family and their counter molecules that are upregulated on the endothelium during an inflammatory state.

10. A defect in CD18, the common chain of β2 integrins, leads to the immunodeficiency disorder leukocyte adhesion defect (LAD). How would you test for this defect?

RECOMMENDED APPROACH

Implications/Analysis of Family History

An inquiry into TC’s family history revealed that no other family members had presented with these types of infections. The absence of familial presentation does not rule out an autosomal recessive disorder because both parents would need to be carriers of the defective gene. That is, both parents could be immunologically normal but each have one defective and one normal gene for the responsible gene (e.g., CD18, see later). TC would have had to inherit the two defective genes. A new mutation, however, cannot be excluded as a cause of the disorder.

Implications/Analysis of Clinical History

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