Antigen Delivery to Lymph Nodes by Dendritic Cells

Dendritic Cell Maturation

Dendritic cells (DCs) are key players in the immune system, responsible for capturing antigens and presenting them to T cells to initiate an immune response. There are two main stages in the life cycle of dendritic cells: immature and mature.

1. Immature dendritic cells: These are dendritic cells that reside in peripheral tissues, such as the skin, mucosa, and internal organs. In this stage, immature dendritic cells have a high capacity for antigen capture but low expression of co-stimulatory molecules and major histocompatibility complex (MHC) molecules. They constantly sample their environment for antigens through processes like phagocytosis and pinocytosis.
2. Mature dendritic cells: Upon encountering pathogens or inflammatory signals, immature dendritic cells undergo maturation. During maturation, dendritic cells upregulate the expression of co-stimulatory molecules and MHC molecules, enhancing their ability to activate T cells. Mature dendritic cells migrate from peripheral tissues to secondary lymphoid organs, such as lymph nodes, where they present antigens to T cells and initiate adaptive immune responses.

Two Lymph Node Entry Points for DCs

Mature dendritic cells can enter lymph nodes through both afferent lymphatic vessels and high endothelial vessels (HEVs), but the relative frequency of each route depends on various factors including the nature of the immune response and the location of antigen encounter.

1. Afferent lymphatic vessels: Dendritic cells from peripheral tissues can migrate to draining lymph nodes via afferent lymphatic vessels. This route is commonly used by dendritic cells that encounter antigens in peripheral tissues such as the skin, mucosa, and internal organs. Dendritic cells in peripheral tissues capture antigens and migrate to nearby lymphatic vessels, where they travel through the lymphatic system to reach draining lymph nodes. This pathway is particularly important for dendritic cells encountering antigens in tissues distal from lymph nodes.
2. High endothelial vessels (HEVs): High endothelial vessels are specialized blood vessels found in lymph nodes. They serve as entry points for lymphocytes, including dendritic cells, from the bloodstream into the lymph node parenchyma. Dendritic cells can enter lymph nodes through HEVs if they encounter antigens in the bloodstream or if they traffic from other lymphoid tissues. This route is particularly relevant for dendritic cells encountering systemic infections or antigens that have disseminated widely throughout the body.

DCs Take the Lymph Vessel Route

Dendritic cells move from peripheral tissues to lymph nodes through a process called migration, which involves several steps:

• Sensing pathogens or inflammation: Immature dendritic cells in peripheral tissues detect pathogens or inflammatory signals through pattern recognition receptors (PRRs) and other sensing mechanisms.
• Maturation: Upon sensing pathogens or inflammation, dendritic cells undergo maturation, characterized by upregulation of co-stimulatory molecules and MHC molecules.
• Migration: Mature dendritic cells migrate from peripheral tissues to lymph nodes through a process called chemotaxis, guided by chemokines and other signaling molecules. They move along chemokine gradients towards lymphatic vessels.
• Entry into lymphatic vessels: Dendritic cells enter lymphatic vessels through a process called lymphatic homing, facilitated by molecules like CCR7 and its ligands CCL19 and CCL21, which are expressed on the surface of both dendritic cells and lymphatic endothelial cells, respectively.

DCs Take the Blood Vessel Route

High endothelial venules (HEVs) are specialized blood vessels found in lymph nodes. They have a unique structure that facilitates the entry of lymphocytes, including dendritic cells, from the bloodstream into the lymph node parenchyma. HEVs are characterized by cuboidal endothelial cells with a high expression of adhesion molecules such as peripheral node addressin (PNAd) and chemokines like CCL21.

Cells, including dendritic cells, enter the lymph node if they use HEV as an entry point by following these steps:

• Rolling: Dendritic cells circulating in the bloodstream initially adhere to the endothelial cells of HEVs through interactions between adhesion molecules such as selectins and their ligands.
• Firm adhesion: Dendritic cells firmly adhere to the endothelial cells of HEVs through interactions between integrins and their ligands.
• Diapedesis: Dendritic cells migrate through the endothelial layer of HEVs and enter the lymph node parenchyma, guided by chemokine gradients and other signaling molecules.

Once inside the lymph node, dendritic cells interact with CD4+ T cells and initiate adaptive immune responses by presenting antigens (signal 1) and providing co-stimulatory signals (signal 2).

Next Topic: Lymph Node Anatomy

Source: ChatGPT response prompted and edited by Joel Graff.

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