The immune system detects and neutralizes threats like viruses and abnormal cells. This relies on specialized cells communicating to initiate protective responses. A key event is the initial encounter between immune cells and foreign substances, known as antigens, often occurring in specific body locations.
Lymph Nodes as Immune Hubs
Lymph nodes are small, bean-shaped organs that filter lymph fluid, which circulates throughout the body. These nodes are strategically positioned, with individuals typically having 400 to 800, allowing immune cells easy access.
Each lymph node is encased in a fibrous capsule and organized into distinct compartments: the cortex, paracortex, and medulla. The outer cortex contains B-cell areas (follicles). The paracortex is predominantly populated by T cells and dendritic cells. The innermost medulla acts as an exit point for filtered lymph and activated immune cells. This structured arrangement facilitates efficient interactions.
Dendritic Cells: Antigen Presenters
Dendritic cells (DCs) are specialized immune cells that initiate adaptive immune responses. They reside in peripheral tissues, such as the skin and mucous membranes, acting as sentinels for infection or tissue damage. Upon encountering foreign invaders or inflammatory signals, immature DCs capture antigens through phagocytosis.
Once they capture antigens, dendritic cells undergo a maturation process. During this, they upregulate molecules essential for activating T cells and then migrate from peripheral tissues. They travel through afferent lymphatic vessels to the nearest draining lymph node. This transforms them into efficient antigen-presenting cells.
T Cells: Immune Responders
T cells are lymphocytes central to cell-mediated immunity. Naive T cells, which have not yet encountered their specific antigen, continuously circulate throughout the bloodstream and lymphatic system, surveying for infection.
Naive T cells enter lymph nodes from the bloodstream through specialized blood vessels called high endothelial venules (HEVs). These HEVs have unique endothelial cells that express adhesion molecules, enabling T cells to enter the lymph node parenchyma. Once inside, T cells migrate through the lymph node, searching for antigens presented by other immune cells.
The T Cell Zone: Where Encounters Begin
The primary location where T cells first encounter antigens is the lymph node’s paracortex, often called the T cell zone. This region serves as a convergence point for naive T cells entering from HEVs and antigen-laden dendritic cells migrating from infected tissues. Dendritic cells, after entering the lymph node, primarily home to the outer paracortex.
The T cell zone has a dense network of fibroblastic reticular cells (FRCs) that guide T cell migration and facilitate interactions. FRCs also produce chemokines like CCL19 and CCL21, which attract T cells and dendritic cells to this area and promote their motility. This strategic positioning and guiding molecular cues increase the likelihood of antigen-specific T cells encountering their antigen.
Antigen Presentation and T Cell Activation
When a naive T cell and an antigen-presenting dendritic cell meet in the paracortex, recognition occurs. Dendritic cells display processed antigen fragments on Major Histocompatibility Complex (MHC) molecules, specifically MHC class I or MHC class II. T cells possess a unique T cell receptor (TCR) that recognizes and binds to a specific MHC-antigen complex.
For full T cell activation, this initial TCR-MHC-antigen binding, known as signal one, is not sufficient. An additional co-stimulatory signal is required. Dendritic cells provide this second signal through the interaction of co-stimulatory molecules on their surface with corresponding receptors on the T cell. The presence of both signals ensures T cells activate only in response to genuine threats, not self-antigens. This dual-signal requirement initiates a targeted immune response, leading to T cell proliferation and differentiation.