Jean-Baptiste Emanuel Zorg, otherwise known as Zorg, was 17 years old when first seen at the Children’s Hospital. He had severe bronchiectasis (dilatation of the bronchi from repeated infections) and a persistent cough that produced yellow-green sputum. Zorg had been chronically ill from the age of 4 years old, when he started to get repeated viral infections of the sinuses, middle ears, and lungs. Interestingly, his brother Mangalore, aged 7 years, also suffered from chronic respiratory infections. Like his brother, he had begun to suffer severe repeated viral infections of the upper and lower respiratory infections at an early age and showed signs of severe bronchiectasis. As infants in Europe, both Zorg and Mangalore received routine immunizations for poliovirus, diphtheria, pertussis, tetanus, measles, mumps, rubella, and tuberculosis and tolerated all of these immunizations well. They also showed ample antibody titers to the vaccines. When Zorg and Mangalore were examined, they both had elevated levels of IgG, at more than 1500 mg/dl (normal levels 600-1400 mg/dl). They had white blood cell counts of 7000 and 6600 cells/μl, respectively. Of these cells, 25% (1750 and 1650 cells/μl, respectively) were lymphocytes and it was determined that only 10% of these cells were cytotoxic T cells (a profound deficiency in CD8 T cells). Blood tests on siblings and parents showed no deficiency of CD8 T cells. It was also determined that both Zorg and Mangalore had normal neutrophil function and complement titers. Evaluation of their CD4 T cell response indicated a normal response and antibody levels were also normal. Because a deficiency in CD8 T cell response was suspected as the etiology of the recurrent infections, white blood cells were evaluated for MHC typing. While MHC class II molecules were expressed normally, neither Zorg nor Mangalore expressed any MHC class I molecules on their cells. Subsequent genetic testing of Zorg and Mangalore identified a deleterious mutation in the genes for calnexin and calreticulin production, which resulted in a loss of MHC class I being expressed on their cells.

Questions

a). Why would a loss of MHC class I result in an increased susceptibility to viral infections?

b). Why did Zorg and Mangalore still have a robust protective response to the vaccine components that were received?