IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 14. Immunological Tolerance

INDUCTION OF TOLERANCE AS A POTENTIAL THERAPEUTIC APPROACH

Further elucidation of tolerance mechanisms is essential for advancing a wide range of applied research fields. It will facilitate the search for Methods to enhance tolerance to foreign grafts and to restore impaired immune Functions in hypersensitivity and autoimmune conditions. Various approaches for inducing artificial tolerance in animals have been explored with an eye toward potential medical Applications. Notable success has been achieved in transplantation involving chimerism through The Use of immunosuppressive agents. The experimental use of non-depleting anti-CD4 and anti-CD8 Monoclonal Antibodies in Organ and tissue transplantation has also proven successful. Clinical trials are forthcoming for animal-tested methods of tolerance induction via targeted mucosal antigen administration or the use of peptide antagonists.

It is equally important to find ways to activate T Cells that "ignore" certain Antigens, thereby stimulating an active Immune Response against them. This would help to constrain the growth of tumors that may express their own unique, tumor-specific antigens.

Questions for Structure/133.html">Discussion

■ How do autoreactive lymphocytes evade immune system control?

■ Why do circulating autoreactive lymphocytes typically fail to cause autoimmune disease?

■ What are the mechanisms of autoaggression, and how can it be prevented or minimized?

■ Why does The Immune System "overlook" antigens expressed by tumor cells?

Introduction/47.html">Further Reading

Goodnow С. 1992. Transgenic Mice and analysis of В Cell tolerance. Anna. Rev. Immunol. 10: 489-518.

Kruisbeek A.M., Amsen D. 1996. Mechanisms underlying T-cell tolerance. Curr. Opm. Immunol. B: 233-44.

Miller J.E.A.P., Basten A. 1996. Mechanisms of tolerance to self. Curr. Opin. Immunol. 8: 815-21.

Nossal G.J.V. 1994. Negative Selection of lymphocytes. Cell 76: 229-39.

Rocken M., Shevach E.M. 1996. Immune deviation-the third dimension of nondeletional T cell tolerance. Immunol. Rev. 149: 175-94.

Schwartz R.H. 1996. Models of T cell anergy: is there a common molecular mechanism? J. Exp. Med. 184: 1-8.