View larger version (53K):
[in a new window]
|
Figure. Oral lymphoid foci (OLF): local site for induction of immunity vs. tolerance? Analysis of inter-papillary tissue in chronic adult periodontitis (CAP) reveals an organizational structure that we have termed OLF. OLF consist of: (i) Langerhans cells (LC) and   T-cells in the epithelium, with double-positive maturing CD1a+CD83+ LC just under the basement lamina; (ii) dermal dendritic cells (DDC) and macrophages infiltrate the lamina propria, with double-positive dendritic-cell-specific ICAM-3-grabbing non-integrins (DC-SIGN + CD83 + dermal dendritic cells (DDC) deeper within the lamina propria; (iii) immune conjugates are formed in the lamina propria, consisting of CD83+DC and B-cells and naïve and memory CD4+ T-cells; (iv) plasma cells infiltrate the lamina propria, while polymorphonuclear leukocytes (PMN) migrate through and out of the gingival crevice. Shown is the ability of P. gingivalis and its pathogen-associated molecular patterns (PAMPs) (e.g., lipopolysaccharide [LPS], fimbriae [fim]) to invade the gingival/pocket epithelium and gain access to LC. Toll-like receptors (TLRs) and C-type lectin receptors (CTLRs) expressed by DDCs play counter-regulatory roles in responses to bacteria, their PAMPs. TLRs stimulate DC activation, leading to expression of co-stimulatory molecules (CD40, CD80, CD86), maturation (CD83), and secretion of IL-12, TNF , all of which favor a Th1 effector response. CTLRs function specifically to take up bacteria and self-antigen (Ag), but lack Toll-Interleukin-1R (TIR) activation domains for DC maturation and cytokine secretion, thus favoring a Th2 or regulatory (Treg) response. The cross-talk between TLR and CTLRs is a ’toggle switch’ between immunity and tolerance.
|
