Lymphoid Tissue Equivalent

In a natural human immune system, the lymph nodes are activated when the body is threatened by a pathogen, producing lymphocytes that help the body fight off infection. In MIMIC™ systems, the lymph nodes' role is played by the Lymphoid Tissue Equivalent (LTE), an immunological tissue construct that mimics a lymph node. When the potent antigen-presenting dendritic cells reverse transmigrate back through the vaccination site's endothelium, they are extracted using a pipette and placed into the LTE.

In its current form, the LTE comprises T and B cells. When the DCs present their antigen to the right receptor-matched T cells, a chain reaction occurs: the antigen activates the T cells, which then activate the B cells to form antibodies. Immune stimulation results in the production and release of cytokines by lymphocytes. These cytokines and antibodies are testable predictive immune responses. After these cytokines are produced in the LTE, they are then removed for testing and classification based on whatever criteria needed.

Mimicking Lymph Node Functionality

The core module for MIMIC™ systems is the Lymphoid Tissue Equivalent (LTE). In the human body, two- and three-way interactions of key cells (dendritic cells, B and T cells) occur in spatially segregated regions of the lymph nodes in a sequential order. These are important considerations if one is to develop a model to test human immunity in a model system. The LTE is an engineered tissue construct that is essentially an artificial lymph node. The LTE merges the right cell growth media with the appropriate cells in a suitable microenvironment.

Cutaway view of the interaction between the vaccination site, lymphoid tissue equivalent, and a 3D tissue-engineered disease model.

After the antigen presenting cells become activated in the VS, the media containing the activated dendritic cells is removed from the VS and placed into the LTE module. In the LTE, the dendritic cells induce antigen-specific cell expansion and cytokine production of T cells, and expansion, differentiation, and production of antigen specific antibodies for B cells. The activated lymphoctyes, cytokine profiles, and antibodies are fully characterized using well-accepted, commercially available methods (FACS, ELISpot and ELISA). Results are typically available within 7–21 days.