IMMUNOLOGY - Roitt A. - Mir 2000

Chapter 13. Regulation of the Immune Response

ANTIGEN-PRESENTING CELLS

The Nature of APCs performing initial antigen presentation can determine the type of response elicited—a full Immune Response or tolerance. Effective T-Cell activation requires the presence of costimulatory molecules on the APC surface (see Chapter 11). Therefore, antigen presentation by dendritic Cells or activated macrophages, which express high levels of MHC Class II Antigens alongside costimulatory molecules, leads to highly efficient T-cell activation (see Fig. 11.4). Furthermore, the interaction between CD40L molecules expressed On the surface of activated T Lymphocytes and CD40 on The surface of dendritic cells ensures robust production of IL-12 by the latter, which is essential for an effective Th1 response. Conversely, when antigens are presented to T cells by "non-professional" APCs that lack the capacity to provide costimulation, unresponsiveness or immune deviation ensues. For instance, antigen presentation to naive T cells by resting B lymphocytes results in T-cell tolerance rather than activation. Adjuvants can promote The Development of immune responses by inducing the high-density expression of MHC antigens and costimulatory molecules on the APC surface. This is illustrated by recent experiments investigating the mechanisms of tolerance in newborn animals, which are more susceptible to tolerance induction than adults. These studies demonstrated that resistance to EAE induced by administration of MBP in incomplete Freund's adjuvant is associated with the development of a dominant Th2 response. While Th1 cells are implicated in the Pathogenesis of EAE, a preceding Th2 response to MBP prevents the pathological Th1 response.

Structure/19.html">The Importance of dendritic cells in inducing a cytotoxic T lymphocyte (CTL)-mediated response was established in experiments involving The transfer of cells from male to newborn female mice. Females that received splenocytes failed to mount a CTL response upon subsequent challenge with male H-Y antigen. In contrast, the transfer of dendritic cells ensured the development of a robust, H-Y-specific CTL response.