The immune system as a self-centered network of lymphocytes

Abstract

This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a "template" for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex "information processing networks" in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance.

Keywords: Autoimmunity; B cells; Immune networks; Immunology; Self-peptides; T cells.

Fig. 1

The formation of immune Information Processing Networks: The B and T cell repertoire are formed in relative isolation during fetal life (Top). The transition of one stage into another during repertoire development are indicated by blue arrows. This relative independence is visible in formation of the B repertoire and B cell idiotypic network by fetal and neonatal B cells around birth (Top right). Soon, after birth, both repertoires start to interact with each other (B:T cell interactions) and environmental factors, promoting the coalescence of the T:B repertoire (Middle panel). The neonatal idiotype anti-idiotype interactions of the early B cell repertoire are now diluted by T:B, stroma and APC cell interactions. This leads to a coalescence of APCs and the B and T cell repertoires with formation of IPNs (Bottom panel). A basic simplified immune IPN based on the studies of the response to influenza in mice presented in “Immune networks and immune cell populations” is shown here. Stimulatory interactions are presented by green arrows and inhibitory interactions by black bloquing lines. Treg cells (TR) (red) are suppressive for Th1-like cells (Green) but stimulate the differentiation of T_FH (Blue) which promote the production of high affinity antigen specific antibodies. These antigen-specific B cells stimulate the formation of more regulatory T cells which stimulate more T_FHs. An inhibitory loop is promoted when B cells differentiate into plasma cells (P cells) which inhibit T_FH cells. Other potential regulatory loops are shown between TR and immature DCs (imDC) or mature DCs (mDC) and T cells. Depicted in each cell population are “public” (triangles) and “private” (small dots) self-peptides in their MHC class I and Class II antigens and B cell epitopes (squares). The recognition of these self-peptides by T cells should promote the indexing of the T cell to the APC that presents the self-peptide. The figure presented here is not intended as an exact description of lymphoid tissue development but only as a guide to the formation of the repertoires and IPNs.