Dendritic Cells: Immune Response and T Cell Activation Explained

Dendritic cells are key players in the immune system, acting as sentinels that detect and respond to pathogens. They bridge innate and adaptive immunity by capturing antigens and presenting them to T cells, orchestrating a targeted immune response.

Their ability to activate T cells makes dendritic cells essential for initiating and regulating immune responses against infections and tumors. Understanding their function is important for advancing immunotherapy and vaccine development.

Phagocytosis Mechanism

Dendritic cells are adept at engulfing and internalizing foreign particles through phagocytosis. This process begins when dendritic cells recognize pathogen-associated molecular patterns (PAMPs) on microbes. These patterns are detected by pattern recognition receptors (PRRs) on the dendritic cell surface, triggering the engulfment process. Once a pathogen is recognized, the dendritic cell membrane extends around the particle, forming a phagosome, a vesicle that encases the pathogen.

Following the formation of the phagosome, it matures by fusing with lysosomes to form a phagolysosome. This fusion exposes the engulfed material to hydrolytic enzymes and reactive oxygen species within the lysosome. These components work together to degrade the pathogen into smaller fragments. The acidic environment within the phagolysosome further aids in the breakdown of the pathogen.

Antigen Processing

Once dendritic cells have dismantled pathogens within phagolysosomes, they begin antigen processing, generating peptide fragments from the degraded pathogen. These peptides are crucial because they will be displayed on the dendritic cell surface. Proteolytic enzymes break down proteins into peptides, which are transported into the endoplasmic reticulum.

Within the endoplasmic reticulum, these peptides encounter major histocompatibility complex (MHC) molecules. MHC molecules bind to the peptides and form stable complexes. These complexes navigate through the Golgi apparatus, undergoing modifications that prepare them for transport to the cell surface. Once they reach the cell membrane, the peptide-MHC complexes are displayed for interaction with T cells.

Role in Adaptive Immunity

Dendritic cells serve as architects of adaptive immunity, orchestrating a response that tailors the body’s defense mechanisms to specific pathogens. Their ability to process and present antigens primes them for this role, acting as intermediaries between the innate immune system and the adaptive arm. This bridging function involves a dynamic interaction that educates and influences T cells, setting the stage for a targeted immune response.

The initiation of adaptive immunity by dendritic cells is marked by the expression of co-stimulatory molecules on their surface. These molecules are essential for the activation of naïve T cells, ensuring that the immune response is specific and robust. By presenting antigens with these co-stimulatory signals, dendritic cells provide cues that guide T cells to differentiate into various effector subsets, such as helper T cells and cytotoxic T cells. Each subset plays a distinct role, from assisting other immune cells to directly attacking infected or malignant cells.

Interaction with T Cells

Dendritic cells shape the immune landscape through their interactions with T cells. Upon migrating to lymphoid tissues, they seek out T cells to present processed antigens. This encounter is facilitated by chemokines that guide T cells toward them, ensuring the interaction occurs in an environment rich in immune signaling molecules. Once T cells are in proximity, dendritic cells engage them through a precise molecular dialogue.

This communication is mediated by the bonding between T cell receptors and the antigen-MHC complexes displayed by dendritic cells. The specificity and strength of this interaction determine whether a T cell will become activated. Beyond antigen presentation, dendritic cells release cytokines that influence T cell behavior. These factors can skew T cell differentiation, promoting either a pro-inflammatory or regulatory response depending on the immune challenge.

Cross-Presentation

Dendritic cells possess the ability known as cross-presentation, allowing them to present extracellular antigens on MHC class I molecules, typically reserved for intracellular antigens. This ability is significant in antiviral and anticancer immune responses, where presenting tumor or viral antigens to cytotoxic T cells can lead to their activation and the elimination of infected or malignant cells. Cross-presentation expands the scope of antigens that dendritic cells can present, enhancing their capacity to initiate diverse immune responses.

The mechanism of cross-presentation involves several pathways, including the endosomal and cytosolic pathways. In the endosomal pathway, extracellular antigens are internalized and processed within endosomes before being loaded onto MHC class I molecules. Alternatively, in the cytosolic pathway, antigens escape from endosomes into the cytosol, where they are degraded by the proteasome. The resulting peptides are then transported into the endoplasmic reticulum via the TAP transporter, where they bind to MHC class I molecules. This flexibility in antigen processing pathways underscores the adaptability of dendritic cells in tailoring immune responses to various challenges.