Describe the role of properdin in complement fixation | Homework Helpers

Mary is 20 months old and has been hospitalized with a fever, irritability, and moderate dehydration. Blood work suggests a bacterial infection, with elevated neutrophils (>96%; normal: ~70%), although the chest radiograph and urinalysis are normal. Computed tomography (CT) indicated intracranial evidence for generalized edema with some compression of the ventricles. Despite the risk associated with elevated cerebrospinal fluid (CSF) pressure, a lumbar puncture was performed that showed an elevated white cell count. An analysis of the CSF by polymerase chain reaction (PCR) assay revealed the presence of Neisseria meningitidis. Mary has been receiving intravenous antibiotics for 30 hours, and there is some improvement in her condition. Query into the child’s background indicated that Mary had been breast fed until she was 3 months of age and had been relatively healthy until this recent infection. Detailed family history reveals that a distant male cousin and an aunt both died at an early age (<2 years) of meningitis.

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1) Mary has a genetically linked immunodeficiency. Unlike many such patients, who had recurrent infections with several gram-negative and/or gram-positive bacteria, Mary has only presented with infection with Neisseria meningitidis. Why is a phagocyte or B cell defect unlikely?

2) The family history revealed that both males and females had presented with this type of infection. What does this indicate? Explain the term autosomal recessive.

3) What molecule or molecules is/are likely missing or defective in Mary?

4) Diagram the alternative pathway of complement fixation.

5) How would deficiencies in the early components of the alternative pathway of complement fixation present clinically?

6) Why is a genetic defect in C3 so devastating?

7) How would a deficiency in CD59 present clinically?

8) List the factors that are responsible for protecting human cells from complement fixation?

9) Describe the role of properdin in complement fixation, and the significance of the fact that the gene that encodes properdin is located on the X chromosome.

10) Why do phagocytes have receptors for modified portions of the C3 and C4 proteins?

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