Innate and adaptive immune pathways to tolerance.

There is a vast scientific literature on the innate and adaptive immune responses that contribute to the development of tolerance with growing appreciation that innate and adaptive immunity do not function independently of each other. Innate immune pathways of current interest are those involving pattern recognition receptors, such as Toll-like receptors, particularly their expression by epithelial cells and dendritic cells at mucosal surfaces. The study of adaptive immune pathways has traditionally focused on specific IgA and the development of effector T-cell populations: the Th1/Th2 paradigm has evolved to encompass Th17 cells. Recent years have seen a dramatic resurgence in the investigation of regulatory T-cell populations that can modify a broad range of immunological activities. Dendritic cells play a key role in linking innate and adaptive immunity. The microenvironment of the dendritic cell at the time of antigen encounter modulates co-stimulatory molecule expression and cytokine production which orchestrate antigen-specific activity by T cells, especially the development of different effector T-cell populations (Th1/Th2/Th17) or regulatory T cells. Cascades of cytokines/chemokines play central roles in many types of immune responses. These include: (i) TGF-beta; (ii) IL-10, and (iii) thymic stromal lymphopoietin (TSLP). Current paradigms of immunity and tolerance in relation to the development of allergy relate to the interplay between innate and immunoregulatory mechanisms.