Abstract
Modeling immunity in vitro has the potential to be a powerful tool for investigating fundamental biological questions, informing therapeutics and vaccines, and providing new insight into disease progression. There are two major elements to immunity that are necessary to model: primary immune tissues and peripheral tissues with immune components. Here, we systematically review progress made along three strategies to modeling immunity: ex vivo cultures, which preserve native tissue structure; microfluidic devices, which constitute a versatile approach to providing physiologically relevant fluid flow and environmental control; and engineered tissues, which provide precise control of the 3D microenvironment and biophysical cues. While many models focus on disease modeling, more primary immune tissue models are necessary to advance the field. Moving forward, we anticipate that the expansion of patient-specific models may inform why immunity varies from patient to patient and allow for the rapid comprehension and treatment of emerging diseases, such as coronavirus disease 2019.
Highlights
Bone marrow three aspects that need to be considered when generating an in vitro or ex vivo model of immunity: immune compartments, types and timescales of immunity, and biophysical and biochemical inputs
If a naive T cell finds its antigen on an activated antigenpresenting cells (APCs), it becomes activated and begins a program of differentiation and/or proliferation that leads to an effector immune response
We have described here several types of systems in which to study and model immune interactions, including ex vivo cultures, chips, and engineered tissues
Summary
From a physical science and engineering perspective, the immune response is a fascinating integration of both biochemical and biophysical inputs (Figure 2). Cells of the immune system communicate largely via receptor-ligand binding, either via physical cell–cell contact or by exchange of secreted proteins, vesicles, and small molecules. Cytokines and chemokines undergo diffusion, convection, active transport, and binding to the extracellular matrix (ECM) [16, 17]; their local concentrations heavily a Receptor-ligand binding b Matrix stiffness c Flow and shear response d Cell–cell contacts. Immune cells are responsive to biophysical cues, including (b) local tissue stiffness, (c) the presence or absence of interstitial fluid flow, and (d) physical contact with neighboring cells. Neutrophils are shown to migrate in the direction of flow via the αvβ integrin [23], demonstrating the varying responses of immune cells to flow
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