![]() In a biological world, different cell types form a stable circuit if they constitutively share information via exchange of molecules. Notably, immune cells respond to instructions from extracellular environment to exercise plasticity in choosing specific cell subsets to launch a dynamic immune response that fits ad hoc to input information ( 2). In terms of the information theory, this process may be represented as a communication channel for computation. In other words, immune cell subsets located in proximity can be organized into a unit of mutual receiver-sender modules. Thus, lymphocytes scan the environment for information from other cells as their input and vice versa. It requires cooperativity from different immune cell subsets.Ī repertoire of membrane receptors along with a milieu of intracellular secretory molecules provide input signals to drive various transcriptional master regulators that commit lymphocyte subsets to send a certain array of outputs. This cannot be tackled by homotypical nodes of lymphocytes acting in isolation. A multitude of cues guide this process: what is the nature of antigen? What is the dose of antigen? Is the antigen self or foreign? What is the appropriate magnitude of response to the antigen? When will the immune contraction phase start? These questions guide the selection of cellular subsets and molecules to launch an appropriate immune response in a universe of diverse antigens. Upon a pathological insult, both cellular and humoral immune responses develop through a typical Darwinian selection process. Therefore, organizing functional modules into networking units lets the immune system accomplish a broader task at the level of organism without disturbing organismal homeostasis ( 2). Signals mediated by acting-at-a-distance molecules or juxtaposing intercellular contacts lead to formation of responsive modules necessary for the execution of effector functions. The organization of immune cells into a social network ( 1) underscores the functional complexity inherent in its design to defend against any pathological noxa. Here, we present the cellular modules that underlie the CTL–NK circuitry to maximize their effector cooperativity against stressed or cancerous cells. Both CTL and mature NK cells undergo membranous reorganization and express various effector molecules to eliminate aberrant cells undergoing a stress of transformation, infection or other pathological noxa. A highly calibrated maturation enables NK cells to eliminate target cells with lowered or absent MHC-I or induced MHC-I-related molecules while maintaining their tolerance toward self-MHC. By contrast, NK cells lack antigen-specific receptors but express a repertoire of highly polymorphic and polygenic inhibitory and activating receptors that bind various ligands including MHC and like molecules. Upon TCR engagement with MHC-I:peptide at a threshold of avidity, T cell intracellular programs converge into cytolytic activity. The CTL carry antigen-specific T cell receptors (TCR) to recognize cognate peptides bound with major histocompatibility complex class-I (MHC-I) or human leukocyte antigen (HLA) molecules on target cells. Cytotoxic innate lymphoid natural killers (NK) and adaptive CD8 + T lymphocytes (CTL) interact to elicit specific cytolytic outcomes. Multiple effector layers in the immune system ensure an optimal temporal and spatial distribution of immune defense. 4Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University School of Medicine, Nashville, TN, United States.3Vanderbilt Center for Immunobiology, Vanderbilt University School of Medicine, Nashville, TN, United States.2Host-Tumor Interactions Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States.1Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, School of Medicine, Meharry Medical College, Nashville, TN, United States.
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