ht Student Hub MSU Denver Case Study 3: The Case of lean-Baptiste Emanuel Zorg:
ID: 194437 • Letter: H
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ht Student Hub MSU Denver Case Study 3: The Case of lean-Baptiste Emanuel Zorg: The Consequences of a Small Flaw in the MHC Due in class April 10, 2018 20 pts Case Study Details 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, mupps, rubella, and tuberculosis and tolerated all of these immunizations well. They also ample antibody titers to the vaccines When Zorg and Mangalore were examined, they both had elevated levels of lgG, at more than 1500 mg/di (normal levels 600-1400 mg/dl). They had white blood cell counts of 7000 and 6600 cells/, respectively. Of these cells, 25% (1750 and 1650 cells/pl, respectively) were lymphocytes and it was determined that only 10% of these cells were cytotoxic T cells (a profound deficiency in CDB T cells). Blood tests on siblings and parents showed no deficiency of CDB 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 CDB 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 1 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 1. What are calnexin and calreticulin? What are their involvement in MHC class 17 Why would their loss result in a deficiency in MHC class I expression on a cell? 2. How would a loss of MIHC class I affect an individual immunologically? What aspects would be affected. Please be specifie in your response 3. Why would a loss of MIIC class I specifically result in an increased susceptibility to viral 4, why were Zorg and Mangalore still able to have robust protective response to the vaccine components that were received regardless of their loss of MHC I? MacBook AirExplanation / Answer
Answer 1: Calnexin and calreticulin are two major chaperones involved in the assembly of class I. Calnexin is important in early stages of MHC class I assembly where it recruits Erp57 to facilitate disulphide bond formation in class I MHC and protects class I MHC from degradation prior to their assembly with 2m. In addition, assembly of class I MHC with 2m is reduced in the absence of calnexin suggesting a direct involvement of calnexin in the assembly of MHC with 2m. Calreticulin, on the other hand, is involved in the later stages of MHC class I assembly. Calreticulin-deficient cell line has demonstrated its critical role in the peptide loading of class I molecules. If their is loss of Calnexin and calreticulin it leads to defiecincy of MHC class I molecule assembly and synthesis as well as its expression on cell.
Answer 2: Loss in MHC class I molecule affects the endogenous pathway of antigen processing and presentation to the T helper cell and does not able to generate the immune response against the internally synthesized antigens like viral antigens and tumor antigens and the body is highly succeptible to such diseases.
Answer 3: Viral pathogens are the intracellular pathogens and multiplied with in the host cell, the antigens of these viral pathogens are presented by viral infected cell to T helper cell with the help of MHC class I molecule to generate the immune response against the pathogen. If the MHC class I molecule losses it affects the presention of viral antigens to T helper cell and become more succeptible to viral infections.
Answer 4: Vaccine components are the purified antigens or epitopes which can directly induces the activation of immune cells and leads to develop the active immunity, it does not need to carry the intracellular infection and presention of antigens.
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