Immunology Terms Starting With R

RAG Recombinase is an enzyme complex of RAG1 and RAG2 proteins that catalyzes V, D, and J gene segment recombination, cutting and rejoining DNA in developing lymphocytes to generate the diverse antigen receptor repertoire.

RAG recombinase initiates assembly of functional immunoglobulin and T cell receptor genes by recognizing recombination signal sequences flanking variable, diversity, and joining gene segments and introducing precise DNA double-strand breaks at those sites. Random joining of these segments, combined with imprecise nucleotide additions and deletions at the cut ends, generates an estimated 10^13 to 10^18 possible antigen receptor sequences from a limited number of germline gene segments. Mutations in either RAG1 or RAG2 cause severe combined immunodeficiency, leaving affected infants with no functional T or B cells and requiring bone marrow transplantation within the first year of life.

RAG expression is tightly restricted to developing lymphocytes in the bone marrow and thymus, and successful receptor rearrangement shuts down RAG transcription through allelic exclusion, ensuring each lymphocyte expresses only one receptor specificity. The RAG proteins share structural similarity with bacterial transposases, supporting the hypothesis that adaptive immunity evolved from ancient mobile DNA elements that inserted into a vertebrate ancestor’s genome roughly 500 million years ago.

Reactive Oxygen Species are chemically unstable, oxygen-derived molecules, including superoxide, hydrogen peroxide, and hydroxyl radicals, that phagocytes generate to kill ingested microbes and that also regulate signaling in immune cells at lower concentrations.

Reactive oxygen species are produced primarily during the respiratory burst in neutrophils and macrophages when NADPH oxidase assembles at the phagosomal membrane and transfers electrons from NADPH to molecular oxygen, generating superoxide anions that rapidly dismutate into hydrogen peroxide and hydroxyl radicals. Myeloperoxidase in neutrophil granules converts hydrogen peroxide and chloride ions into hypochlorous acid, the same oxidant found in household bleach, creating a toxic environment that destroys bacterial cell walls and viral proteins within the phagosome. Neutrophils increase their oxygen consumption up to 100-fold during this burst, producing hydrogen peroxide concentrations reaching 400 micromolar inside phagosomes.

At lower, physiological concentrations, reactive oxygen species oxidize cysteine residues in signaling proteins, activating NF-kB-dependent cytokine transcription and modulating T cell receptor signaling thresholds. Chronic granulomatous disease, affecting roughly 1 in 200,000 births, results from inherited defects in NADPH oxidase subunits, leaving patients unable to generate reactive oxygen species and highly susceptible to catalase-positive bacteria such as Staphylococcus aureus and fungi such as Aspergillus fumigatus.

Receptor Editing is a central tolerance mechanism in which immature B cells that bind self-antigens reactivate RAG recombinase to replace their autoreactive light chain with a new sequence, changing the receptor's specificity rather than deleting the cell.

Receptor editing occurs in the bone marrow when an immature B cell’s newly assembled receptor engages self-antigen and receives signals that reactivate RAG1 and RAG2 rather than triggering apoptosis. The RAG proteins cleave the existing light chain locus and recombine upstream V and J segments, replacing the autoreactive light chain while preserving the heavy chain; studies in mouse models estimate that 25 to 50 percent of developing B cells undergo at least one editing event. Some B cells attempt five or more sequential editing rounds, exhausting available kappa locus segments before switching to the lambda locus, and failure at all available loci results in developmental arrest and clonal deletion.

Receptor editing is estimated to rescue approximately half of the autoreactive B cells that would otherwise be deleted, making it a major contributor to the self-tolerant repertoire alongside clonal deletion and anergy. The strength of self-antigen signaling determines the outcome: weak signals favor editing, while strong signals drive apoptosis through clonal deletion.

Regulatory T Cell is a specialized CD4 T cell subset expressing the transcription factor Foxp3 that actively suppresses immune responses by inhibiting effector lymphocyte activation, preventing autoimmunity, and limiting collateral tissue damage.

Tregs develop in the thymus when self-peptide-MHC complexes bind with intermediate affinity, sufficient for positive selection but below the threshold that triggers deletion, producing thymic or natural Tregs. Peripheral Tregs can also be induced from naive CD4 T cells by TGF-beta signaling in tolerogenic environments such as the gut lamina propria. Suppression operates through multiple mechanisms: secretion of IL-10 and TGF-beta, CTLA-4-mediated deprivation of co-stimulatory signals from antigen-presenting cells, and direct cytolysis of effector cells via granzyme B.

Disruption of Foxp3 expression, as seen in the scurfy mouse mutation, causes fatal multi-organ autoimmunity within weeks of birth, demonstrating how indispensable this lineage is for self-tolerance.