In addition, once inside the lymph node, Ag-loaded DCs begin to release specific chemokines (e.g., MDC) to guide proximal active T cells [11,12]. B cell activation is initiated by an engagement of the B cell receptor either by a soluble or a membrane-associated antigen [13,14]. significantly reduced in magnitude. Dendritic cell removal is also shown to delay the response time with respect to normal conditions. == Background == Lymph nodes and Peyer’s patches play key functions in the development of an appropriate and efficient immune response. Once an Antigen (Ag) is usually captured by Ag-processing cells, it is rapidly carried to the nearest lymph node, where it is presented to specific lymphocytes to trigger an immune response. The recognition phase must be highly efficient: within a few hours, it is necessary to find specific lymphocytes among a repertoire that includes a very large number of receptors [1,2]. The specific architecture of the lymph node and a fine-tuned balance between diffusion, chemotaxis, and receptor expression are the basis of this process. Human SKF-96365 hydrochloride lymph nodes are bean-shaped structures that range in size from a few millimeters to about 1-2 cm in their normal state. Internally, two main regions can be distinguished: themedullaand thecortex. The cortex can be further divided into an inner part, theparacortex(also called theT cell area), rich in T lymphocytes and an outer area, thenode cortexthat includes Rabbit Polyclonal to Caspase 14 (p10, Cleaved-Lys222) theB cell areaconsisting of follicles and germinal centers, where B cells are activated and differentiate [3]. T and B areas are identified by high concentrations of different chemokines (CCR7 and CXCR5, respectively) secreted by local stromal cells [1,4,5]. The whole structure is supported by a dense network of fibroblastic reticular cells that encloses small lymphatic channels of 10-15m in diameter SKF-96365 hydrochloride along which small molecules are thought to diffuse [6]. Macrophages, SKF-96365 hydrochloride dendritic cells (DC), and some lymphocytes flow from the afferent lymphatic vessels, through the fibroblastic reticular cellular network, to the node cortex and the medulla, before leaving via the efferent lymphatic vessels. Most T and B cells, however, are too large in size and enter the lymph node mainly from the blood, through high endothelial venules (HEV) located inside the paracortex. During an infection, lymphocyte recruitment from the periphery is enhanced due to a widening of the primary arteriole feeding the lymph node [2]. Once inside the lymph node, B and T cells rapidly home in their own compartments, following a specific chemotactic gradient [1,4]. T helper cells (TH) are the fastest, with an average velocity of 11m/min, followed by B cells with 6m/min and DCs with a velocity of 3m/min [7]. In the absence of an antigenic challenge, T SKF-96365 hydrochloride and B cells randomly scan their respective areas for ~24-48 h before exiting the lymph node [8]. Entrance of antigens into the lymph node triggers a series of events leading to antigen recognition and the activation of an immune response. Two distinct pathways for antigen delivery have been recognized. In general, an Ag-presenting cell picks up the antigen in peripheral tissues and migrates to the nearest lymph node in order to present the MHC-peptide complex to the T and B cells. In addition, antigens of low molecular weight (below 70 kDa) may enter the lymph node as soluble antigens and reach the T cell area directly through the fibroblastic SKF-96365 hydrochloride reticular cellular meshwork, without any preliminary recognition. This delivery system is very efficient, and soluble antigens are detected inside the lymph node within a few minutes of infection. Here, specific resident DCs are able to capture the antigen well before Ag-presenting cells arrive from peripheral organs (on average, 8-12 h later) [9]. The immune response is initiated inside the T cell area, where antigens are first presented to the T cells, generally by DCs. After antigen recognition, peripheral dendritic cells undergo a change in the expression of their surface receptors. In particular, receptors for inflammatory chemokines are lost, and lymphoid receptors, especially the CCR7 receptor, are expressed [10]. As a consequence, Ag-presenting DCs are rapidly routed towards T cell area, where.
