Introduction

Most soluble antigens

Most soluble antigens

Autologous indigenous microflora

Pathogens Particulate antigens

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Pathogens Particulate antigens

(W\AAAiWpAMA/m

Immune exclusion by secretory antibodies

Epithelial barrier

Suppression of proinflammatory IgG, IgE (Th2) and DTH (Th1)

Stimulation of IgA (and IgM)

Mucosally induced ('oral') tolerance

Local

Peripheral

Fig. 14.1. Schematic depiction of two major adaptive immune mechanisms operating at mucosal surfaces. (1) Immune exclusion limits epithelial colonization of pathogens and inhibits penetration of harmful foreign material. This first line of defence is principally mediated by secretory antibodies of the immunoglobulin (Ig)A (and IgM) class in cooperation with various non-specific innate protective factors (not shown). Secretory immunity is preferentially stimulated by pathogens and other particulate antigens taken up through thin membrane (M) cells located in the dome epithelium covering inductive mucosa-associated lymphoid tissue (see Fig. 14.3). (2) Penetrating innocuous soluble environmental and dietary antigens (magnitude of uptake indicated), as well as the autologous indigenous microbial flora, are less stimulatory for secretory immunity (self-limiting responses, broken arrows), but induce suppression of pro-inflammatory humoral immune responses (IgG and T-helper-2 (Th2) cytokine-dependent IgE antibodies), as well as Th1 cytokine-dependent delayed-type hypersensitivity (DTH). The homoeostatic Th1/Th2 balance is regulated by a complex and poorly defined phenomenon called mucosal or 'oral' tolerance (see Fig. 14.5), which exerts down-regulatory effects both locally and in the periphery. (Modified from Brandtzaeg et al., 1999a.)

gut of an adult every year, resulting in substantial uptake of intact antigens even in the healthy state. Nevertheless, the neonatal period is particularly critical in terms of mucosal defence, in regard to both infections and priming for allergic disease (Holt and Jones, 2000). This is so because the mucosal barrier function and the immunoregulatory network are poorly developed for a variable period after birth (Brandtzaeg et al., 1991; Holt, 1995). Notably, the post-natal development of mucosal immune homoeostasis appears to depend on the establishment of a normal commensal microbial flora, as well as on the adequate timing and dose of dietary antigens when first introduced (Brandtzaeg, 1996b, 1998; Helgeland and Brandtzaeg, 2000).

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