ABSTRACT
INTRODUCTION AND THE RATIONALE An Integrated Model of Immune Responsiveness Secondary lymphoid organs, including lymph nodes, spleen, and mucosa-associated lymphoid tissue, are highly organized anatomical structures encompassing a wide variety of bone marrowderived cell types in close proximity. Regulation of immunity in the periphery is largely confi ned to the secondary lymphoid organs and includes the following functions: maintenance of tolerance in a steady-state fashion, homeostatic proliferation, induction and expansion of immune responses, differentiation of effector and memory cells, and retraction of immune responses through tolerance, anergy, or exhaustion. Furthermore, the proximity of complementary immune cell phenotypes is developmentally programmed ( 1 , 2 ) and key to the successful immunoregulatory function of secondary lymphoid organs described earlier.
