Paul's problems with respiratory viruses began when he was about 2 years old.
He was treated repeatedly with antibiotics for middle ear infections and viral
pneumonia. He had been a healthy infant and had had no problems with childhood
immunizations to polio virus, DPT (diphtheria toxoid, Bordetella pertussis
acellular vaccine, and tetanus toxoid), and HIB (Haemophilus influenzae B).
When he was hospitalized for yet another bout with viral pneumonia, his pediatrician
performed some tests to assess the state of his immune system.
Paul's serum IgG and lymphocyte count were slightly elevated. He had circulating IgG antibodies to the DPT antigens and to polio virus. His circulating T lymphocytes were 95% CD4+, compared to a normal ratio of 2:1 CD4+:CD8+ circulating T cells. His B cell and neutrophil counts and his complement functions were normal. His cellular immunity, measured in a skin test to poison ivy which he had had six months previously, was also normal. However, levels of MHC Class I on his white blood cells were reduced by about 90%.
Cell lines produced from Paul's peripheral blood T cells had normal levels of mRNA for MHC class I molecules and b2M. However, no mRNA was found for TAP-1. Without TAP-1, virus peptides could not be transported to the ER to bind MHC I α chain and β2M for presentation on the membrane. Without membrane MHC Class I, development of CD8+ Tc could not occur in Paul's thymus. MHC Class II was presented and CD4+ T cells developed properly. TH1 inflammatory cells and TH2 helper cells were able to provide normal immunity against bacterial and fungal (exogenous) antigens.
1. Flow cytometry is a technique used to quantify circulating leukocytes based on their size, granularity, and cell surface markers (see Janeway Figure A25). Cells labeled with fluorochrome-tagged antibodies to cell surface markers can be counted and the amount of marker on their surfaces measured. The diagram below left shows data for CD8+ cells in normal peripheral blood. The horizontal axis shows fluorescence intensity on a log scale; the vertical axis shows numbers of cells. A "gate" is set indicating all cells considered positive for CD8, in this case 38% of the blood lymphocytes. [Other gates are set to exclude granulocytes and monocytes from being counted.] The diagram at right below shows two-color fluorescence, where anti-CD3 is tagged with PE (phycoerythrin, red) and anti-CD8 is tagged with FITC (fluorescein isothiocyanate, green). The gates are shown by the horizontal and vertical lines, and the % of cells in each box is also indicated.
Draw the two diagrams above as they would appear for Paul's blood lymphocytes. Draw the 2-color flow diagram for Paul's cells substituting CD4 FITC for CD8 FITC.
2. How could Paul make IgG antibodies, which require T cell help, but not be able to respond to viruses?
3. How many alleles of MHC molecules are on a liver cell? on a B cell?
4. How can our T cells respond to so many different peptides when we have so few MHC molecules to present the peptides?
5. CD1 molecules are classified as non-classical MHC. How do they differ from Class I and Class II MHC molecules?
6. What is a superantigen. How is it different from a "regular" antigen?