Dr. Ross was a third year surgical resident at a large urban medical center.
While treating a victim of gunshot wound, Dr. Ross was spattered with the patient's
blood. Unnoticed by Dr. Ross, a small amount of blood ran under her glove and
across a scratch on her wrist. The patient was a drug addict who was infected
with Hepatitis B Virus (HBV). HBV is transmitted by contact with blood or blood
products, by sexual contact, or from mother to fetus. The patient Dr. Ross was
treating contracted HBV from shared drug injection equipment.
HBV is a Hepadnavirus (He PAD na; Hepa = liver, dna = DNA genome). It has a double-stranded DNA genome and a protein capsid (coat). The proteins which make up the outer layer of the coat are called Hepatitis B surface antigen (HBsAg) and those from the inner layer are called the core (HBcAg) and e (HBeAg) antigens. The virus also carries a viral DNA polymerase. Under the electron microscope it is possible to detect round viruses and also smaller round or cylindrical Dane particles, which are polymerized excess capsid protein.
Hospital personnel are generally vaccinated against HBV, but Dr. Ross had been ill when it was time for her second booster and after that too busy studying for her board exams. Most cases of HBV are asymptomatic, as was Dr. Ross's, so she never know she was infected. A minority of infected people develop fever, loss of appetite, abdominal pain, nausea, and fatigue 1-3 months after exposure. The virus infects liver (hepatic) cells and can destroy enough tissue to cause jaundice. It is estimated that there are 200,000 new cases of HBV in the US every year. Of these, 20,000 become chronic carriers who may not have symptoms following the acute infection but who can pass along the virus to others and who may eventually die from cirrhosis (liver damage) or liver cancer.
The table above illustrates the usual appearance of HBV antigens and antibodies
in the blood during and following acute infection. HBcAg is not usually found
in the serum.
1. Describe the expected immune response to HBV. Using the data from the table above, explain the relationship between the humoral immune response to HBV and the presence of HBV antigens and antibodies in the serum.
2. About 5 years after her original infection, chronic abdominal pain sends Dr. Ross to a specialist. He performs extensive tests and finds that Dr. Ross has HBsAg in her blood, suggesting that she is an HBV carrier. This and other information leads to the diagnosis of hepatocellular carcinoma (liver cancer). The specialist calls your lab and asks you for an antibody that can be used to detect (image) the tumor; He has a detector that will localize radioactive signals inside the patient. Describe the kind of antibody you need and how you would make it. Consider the following issues: Is this cancer likely to have tumor-specific antigens? Once you have made your antibody, how can you test it to make sure it binds tumor cells and not normal cells? Could this antibody be used repeatedly in Dr. Ross to follow the progress of her disease? Could it be conjugated with a toxin and used to kill tumor cells? EXPLAIN all your answers.
3. While they wait for you to send them the antibody, Dr. Ross and her physician discuss a liver transplant. Describe the transplantation antigens that must be matched and why matching improves the success of transplants. In addition, discuss what kinds of anti-rejection medications would be needed.
4. Your diagnostic antibody shows the cancer is widely disseminated in the liver and has metastasized to other organs, so it is inoperable. It is also producing TGF-b. All attempts to treat the cancer by irradiation and chemotherapy fail. Dr. Ross is willing to try immunotherapy as a last resort, and you are asked to design a vaccine with Dr. Ross' tumor cells (available from surgical removal of tumor mass). Design and outline a treatment plan and explain how it will stimulate the immune system to fight the tumor. Consider the following issues: Why might Dr. Ross' immune system not have eliminated the tumor on its own? What immune effectors do you want to stimulate and how can they kill tumor cells? How can you make the tumor cells you inject (the vaccine) more immunogenic than the original tumor? What might be the possible side effects of your vaccine? Be as specific as you can about the immune effector cells and molecules involved.
This exam requires a lot of thought - brainstorm the possible answers for each question, pick ONE (for #s 2 and 4 there are several possible approaches), and defend it in depth. Save as a Word document entitled YourNameExam4.doc. Send to jdecker@u.arizona.edu as an email attachment or in the body of the email by noon Thursday July 10. Grades will be available by noon Thurssday, July 8. Make sure your name is in the document as well as in the title.