The Role of Dendritic Cells in TCell Activation

Naive T cells slowly circulate among the secondary lymphoid organs as a means of encountering antigens. Immature dendritic cells, meanwhile, reside in peripheral tissues, such as beneath the skin, gathering various materials from those areas (figure 16.20). The dendritic cells use both phagocytosis and pinocy-tosis to take up particulate and soluble material that could potentially contain foreign protein. After collecting substances from the periphery, the dendritic cells travel to the secondary lymphoid organs to meet T cells; the inflammatory response can trigger the migration. En route to the lymphoid organs, the dendritic cells mature into a form that is able to present antigen to naive T cells. Mature dendritic cells, like macrophages and B cells, are professional antigen-presenting cells. Dendritic cells are unique, however, because the antigens they have collected can be presented by both MHC class I and MHC class II molecules. Because of this, dendritic cells can use engulfed material to activate both T-cytotoxic and T-helper cells. ■ pinocytosis, p. 72

A dilemma lies in the fact that the dendritic cell must only activate a given T cell if the material being recognized by it represents danger. Antigen presentation alone does not convey the significance of the material being displayed; the fragments could be parts of an invading microbe, which would merit an adaptive immune response, or routine cellular debris, which would not. In fact, an immune response to cellular debris would harm the host. The sensors of the innate immune response, such as the toll-like receptors, help solve this dilemma. They enable the dendritic cell to sense the presence of molecules that signify an invading microbe. When a toll-like receptor is engaged by one of these molecules, the dendritic cell produces surface proteins called co-stimulatory molecules. In essence, the co-stimulatory molecules function as "flashing red lights" that interact with the T cell, communicating to it that the dendritic cell is presenting material that signifies danger. Dendritic cells that are producing co-stimulatory molecules while presenting antigen are able to activate T cells. In contrast, a T cell that recognizes a peptide: MHC complex on a dendritic cell that is not producing co-stimulatory molecules may become unresponsive to future encounters with antigen. Recall that inducing this type of unresponsiveness is one of the mechanisms by which the adaptive immune response eliminates those lymphocytes that recognize "self" proteins. ■ toll-like receptors, p. 381

Co-stimulatory molecule

16.8 Natural Killer (NK) Cells 411

MHC class II molecule

T-cell receptor CD8

Particulate and soluble material including microbial fragments (LPS, peptidoglycan)

Dendritic cells in the tissues collect particulate and soluble antigen. When a toll-like receptor is engaged, the cell produces co-stimulatory molecules.

Co-stimulatory molecule

16.8 Natural Killer (NK) Cells 411

MHC class II molecule

Particulate and soluble material including microbial fragments (LPS, peptidoglycan)

Dendritic cells in the tissues collect particulate and soluble antigen. When a toll-like receptor is engaged, the cell produces co-stimulatory molecules.

MHC class I molecule

En route to the secondary lymphoid organs, the dendritic cells mature to become antigen-presenting cells. Peptides from the collected material can be presented by both MHC class I and MHC class II molecules. Dendritic cells that have engulfed microbial fragments produce co-stimulatory molecules. Naive T cells that recognize antigen presented by a dendritic cell that expresses co-stimulatory molecules may become activated, allowing them to proliferate and develop their effector functions.

T-cell receptor CD4

Figure 16.20 Activation of T Cells by Dendritic Cells Expressing Co-Stimulatory Molecules

MHC class I molecule

En route to the secondary lymphoid organs, the dendritic cells mature to become antigen-presenting cells. Peptides from the collected material can be presented by both MHC class I and MHC class II molecules. Dendritic cells that have engulfed microbial fragments produce co-stimulatory molecules. Naive T cells that recognize antigen presented by a dendritic cell that expresses co-stimulatory molecules may become activated, allowing them to proliferate and develop their effector functions.

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