QUESTIONS FOR GROUP DISCUSSION

1. Transplantation is the primary treatment of choice for many diseases. What problems has this created?

2. What are some of the causes of fulminant hepatitic failure (FHF) in infants?

3. What is the sole intervention for FHF?

4. Explain why the pig is a good choice for organ transplantation into humans (at least three reasons).

5. One of the problems arising in transplantation across species is the presence of a carbohydrate structure Galα1-3-Galβ1-4GlcNAc-R (αgalactosyl epitope) in pigs (and many other animals). Explain why humans do not express this carbohydrate structure on cell surfaces.

6. Explain why humans have IgM antibodies specific for this carbohydrate structure, despite the fact that we have not been exposed to pig (or other animal) tissues that express this antigen.

7. Describe the immune response that follows when the transplant recipient’s (host) antibodies bind to the surface of xenografts expressing the α-galactosyl epitope on the surface that leads to hyperacute rejection of the tissue.

8. Explain why transgenic pigs expressing the human form of decay accelerating factor (DAF) have been designed to overcome this problem of hyperacute rejection.

9. There is evidence that any time cells from different species are mixed, a zoonotic infection is possible. What is a zoonotic infection? Explain why attempts to eliminate the immunologic response to the α-galactosyl epitope on pig tissues using DAF transgenic pigs may result in an increased risk of infection with the porcine endogenous retroviruses (PERV).

10. Extrapolate the ideas just discussed to in vitro fertilization egg cultures that are grown on a “feeder” layer of animal cells (e.g., bovine kidney) before reimplantation into the mother.

RECOMMENDED APPROACH

Implications/Analysis of Family History

FD’s mother is a hepatitis B virus (HBV) carrier who was identified during maternal screening and was found to have anti-HBc and anti-HBe IgG antibodies specific for the HBV core and HBe (pre core) antigens (HBcAg and HBeAg, respectively). HBeAg is associated with HBcAg (Fig. 39-1). Additional enzyme-linked immunosorbent assays (ELISAs) revealed that the mother was positive for the HBs antigen (HBsAg) but negative for HBeAg. Had the mother been HBeAg positive, the infant would have been given gamma globulin (anti-HBV antibodies) and the first of the three required HBV vaccine antigens. Because the mother was negative for HBeAg, the child had not been given either therapy, according to the regulations in place. HBsAg may also be detected in liver biopsies (Fig. 39-2).

FIGURE 39-1 Serologic and clinical patterns observed during acute and chronic hepatitis B infection.

(From Murray P, Rosenthal K, Kobayashi Y, Pfaller M: Medical Microbiology, 4th ed. St Louis, Mosby, 2002; redrawn from Hoofnagle JH: Annu Rev Med 32:1–11, 1981.)