References

Adams, D. H. 2000. Cardiac xenotransplantation: clinical experience and future direction. Ann. Thoracic Surg. 70:320.

Auchincloss, H., M. Sykes, and D. H. Sachs. 1999. Transplantation immunology, in Fundamental Immunology, 4th ed. W. E. Paul, ed. Lippincott-Raven, Philadelphia. p. 1175.

Fox, A., and L. C. Harrison. 2000. Innate immunity and graft rejection. Immunol. Rev. 173:141.

Grover, F. L., et al. 1997. The past, present, and future of lung transplantation. Am. J. Surg. 173:523.

Harlan, D. M., and A. D. Kirk. 1999. The future of organ and tissue transplantation: can T-cell co-stimulatory pathway modifiers revolutionize the prevention of graft rejection? JAMA 282:1076.

Hirose, R., and F. Vincenti. Review of transplantation—1999. Clin. Transplants 1999:295.

Hong J. C., and B. D. Kahan. 2000. Immunosuppressive agents in transplantation: past, present, and future. Sem. Nephrol. 20: 108.

Kirk, A. D., et al. 1997. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc. Natl. Acad. Sci. USA 94:8789.

Lenschow, D. J., et al. 1992. Long-term survival of xenogeneic pancreatic islets induced by CTLA4-Ig. Science 257:789.

Markees, T. G., et al. 1997. Prolonged survival of mouse skin allografts in recipients treated with donor splenocytes and antibody to CD40 ligand. Transplantation 64:329.

Mollnes, T. E., and A. E. Fiane. 1999. Xenotransplantation: how to overcome the complement obstacle? Mol. Immunol. 36:269.

Rayhill, S. C., et al. 1996. Simultaneous pancreas-kidney transplantation: recent experience at the University of Wisconsin. Exp. Clin. Endocrinol. Diabetes 104:353.

Woo, S. B.,S. J. Lee, and M. M. Schubert. 1997. Graft-vs-host disease. Crit. Rev. Oral Biol. Med. 8:201.

L WEB SITES

http://www.transweb.org

Links to hundreds of sites giving information on all aspects of organ transplantation.

http//www.unos.org

United Network for Organ Sharing site has information concerning solid-organ transplantation for patients, families, doctors, and teachers.

http://www.marrow.org

The National Marrow Donor Program Web site contains information about all aspects of bone-marrow transplantation.

Study Questions

Clinical Focus Question What features would you include in an ideal animal donor for xenotransplantation? How would you test your model prior to doing clinical trials in humans?

1. Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.

a. Acute rejection is mediated by preexisting host antibodies specific for antigens on the grafted tissue.

L WEB SITES

b. Second-set rejection is a manifestation of immunologic memory.

c. Passenger leukocytes are host dendritic cells that migrate into grafted tissue and act as antigen-presenting cells.

d. All allografts between individuals with identical HLA haplotypes will be accepted.

e. Cytokines produced by host TH cells activated in response to alloantigens play a major role in graft rejection.

2. You are a pediatrician treating a child who needs a kidney transplant. The child does not have an identical twin, but both parents and several siblings are willing to donate a kidney if the MHC match with the patient is good.

a. What is the best possible MHC match that could be achieved in this situation?

b. In which relative(s) might you find it? Why?

c. What test(s) would you perform in order to find the best-matched kidney?

3. Indicate in the Response column in the table on page 500 whether a skin graft from each donor to each recipient listed would result in a rejection (R) or an acceptance (A) response. If you believe a rejection reaction would occur, then indicate in the right-hand column whether it would be a first-set rejection (FSR), occurring in 12-14 days, or a second-set rejection (SSR), occurring in 5-6 days. All the mouse strains listed in the table have different H-2 haplotypes.

4. Graft-versus-host disease (GVHD) frequently develops after certain types of transplantations.

a. Briefly outline the mechanisms involved in GVHD.

b. Under what conditions is GVHD likely to occur?

c. Some researchers have found that GVHD can be diminished by prior treatment of the graft with monoclonal antibody plus complement or with monoclonal antibody conjugated with toxins. List at least two cell-surface antigens to which monoclonal antibodies could be prepared and used for this purpose, and give the rationale for your choices.

5. A child who requires a kidney transplant has been offered a kidney from both parents and from five siblings.

a. Cells from the potential donors are screened with monoclonal antibodies to the HLA-A, -B, and -C antigens in a microcytotoxicity assay. In addition, ABO blood-group typing is performed. Based on the results in the table on page 500, a kidney graft from which donor(s) is most likely to survive?

b. Now a one-way MLR is performed using various combinations of mitomycin-treated lymphocytes. The results, expressed as counts per minute of [3H]thymidine incorporated, are shown in the table on page 500; the stimulation index (ratio of the experimental value to the control in which identical leukocytes are mixed) is listed below in parentheses. Based on these data, a graft from which donor(s) is most likely to be accepted?

6. What is the biologic basis for attempting to use soluble CTL4A or anti-CD40L to block allograft rejection? Why might this be better than treating a graft recipient with CsA or FK506?

Go to www.whfreeman.com/immunology Review and quiz of key terms

Self-Test

For use with Question 3:

Donor

Recipient

Response

Type of rejection

BALB/c

C3H

BALB/c

Rat

BALB/c

Nude mouse

BALB/c

C3H, had previous BALB/c graft

BALB/c

C3H, had previous C57BL/6 graft

BALB/c

BALB/c

BALB/c

(BALB/c X C3H)F-|

BALB/c

(C3H X C57BL/6)Ft

(BALB/c X C3H)F1

BALB/c

(BALB/c X C3H)F1

BALB/c, had previous Ft graft

For use with Question 5a:

Recipient

1 ABOtype

1 HLA-Atype

1 HLA-B type

1 HLA-C type

O

A1/A2

B8/B12

Cw3

Potential donors Mother

A

A1/A2

B8/B12

Cw1/Cw3

Father

O

A2

B12/B15

Cw3

Sibling A

O

A1/A2

B8/B15

Cw3

Sibling B

O

A2

B12

Cw1/Cw3

Sibling C

O

A1/A2

B8/B12

Cw3

Sibling D

A

A1/A2

B8/B12

Cw3

Sibling E

O

A1/A2

B8/B15

Cw3

For use with Question 5b:

Mytomycin C-treated stimulator cells

Respondent cells

Patient

Sibling A

Sibling B

Sibling C

Sibling D

Sibling E

Patient

1,672

1,800

13,479

5,210

13,927

13,808

(1.0)

(1.1)

(8.1)

(3.1)

(8.3)

(8.3)

Sibling A

1,495

933

11,606

8,443

11,708

13,430

(1.6)

(1.0)

(12.4)

(9.1)

(12.6)

(14.4)

Sibling B

25,418

26,209

2,570

13,170

19,722

4,510

(9.9)

(10.2)

(1.0)

(5.1)

(7.7)

(1.8)

Sibling C

10,722

10,714

13,032

1,731

1,740

14,365

(6.2)

(5.9)

(7.5)

(1.0)

(1.0)

(8.3)

Sibling D

15,988

13,492

18,519

3,300

3,151

18,334

(5.1)

(4.2)

(5.9)

(1.1)

(1.0)

(5.9)

Sibling E

5,777

8,053

2,024

6,895

10,720

888

(6.5)

(9.1)

(2.3)

(7.8)

(12.1)

(1.0)

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment