Immunology Terms Starting With L
Immunology Glossary: L
Jump to Immunology Term
LAG3
/ LAG-three / · LAG3: Lymphocyte Activation Gene 3
LAG3 is an inhibitory immune checkpoint receptor expressed on activated and exhausted T cells, natural killer cells, and regulatory T cells that suppresses lymphocyte activation by binding MHC class II molecules and other ligands.
LAG-3 was identified in 1990 by Triebel and colleagues as a CD4-like transmembrane protein that binds MHC class II with higher affinity than CD4 itself. Unlike CD4, LAG-3 contains a unique KIEELE motif in its cytoplasmic tail that delivers inhibitory signals, reducing T cell proliferation and cytokine production. Chronic antigen exposure during persistent viral infection or tumor growth drives co-expression of LAG-3 with other checkpoint receptors such as PD-1 and TIM-3, a state associated with T cell exhaustion.
Relatlimab, an anti-LAG-3 antibody, received FDA approval in 2022 in combination with nivolumab for unresectable melanoma, marking the first approved therapy targeting this checkpoint.
Beyond MHC class II, LAG-3 binds fibrinogen-like protein 1 (FGL1), a liver-secreted protein that many tumors produce at high levels to suppress T cell responses, providing a second mechanism by which LAG-3 limits anti-tumor immunity independent of antigen presentation.
Blocking LAG-3 alone is sufficient to restore full anti-tumor T cell function. In most tumor models, LAG-3 blockade produces only modest effects on its own, and meaningful responses require combining anti-LAG-3 with anti-PD-1 therapy because exhausted T cells co-express multiple checkpoint receptors simultaneously.
In patients with unresectable melanoma enrolled in the RELATIVITY-047 trial, combining relatlimab with nivolumab improved median progression-free survival to 10.1 months compared with 4.6 months for nivolumab alone. Tumor-infiltrating T cells in responding patients showed reduced co-expression of LAG-3 and PD-1 after treatment. These results, published in 2022, established dual checkpoint blockade as a clinically meaningful strategy for this cancer type.
Lymph Node
/ LIMF nohd / · Latin lympha (water) + nodus (knot)
Lymph Node is a small, bean-shaped secondary lymphoid organ distributed throughout the body along lymphatic vessels that filters lymph fluid, traps pathogens and antigens, and is the principal site where adaptive immune activation begins.
Lymph nodes contain distinct anatomical zones: the cortex with B cell follicles and germinal centers, the paracortex with T cells and dendritic cells, and the medulla with macrophages and plasma cells. Dendritic cells carrying antigens from peripheral tissues migrate to the paracortex, where they present peptides to naive T cells and initiate clonal expansion. A single activated T cell can divide to produce thousands of daughter cells within five to seven days, generating the effector population needed to clear an infection.
Enlarged lymph nodes, a condition called lymphadenopathy, indicate active immune responses to local infection, vaccination, or malignancy.
The human body contains approximately 500 to 700 lymph nodes, but their distribution is uneven: roughly 300 are concentrated in the head, neck, and thorax, reflecting the high antigen load those regions encounter from the respiratory and digestive tracts.
Immune System Fun Facts →Swollen lymph nodes signal cancer. Lymph nodes enlarge far more often during bacterial or viral infections because the B cells and T cells inside them are rapidly dividing, and the swelling typically resolves within two to four weeks once the infection clears.
During a streptococcal throat infection in children, cervical lymph nodes commonly enlarge to 1 to 2 centimeters in diameter within 48 to 72 hours of symptom onset. Germinal centers within those nodes can expand over the next 7 days as B cells undergo somatic hypermutation and affinity maturation to produce high-affinity antibodies against streptococcal antigens. This response typically peaks around day 7 and subsides as the infection resolves.
Lymphocyte
/ LIM-foh-syt / · Latin lympha (water) + Greek kytos (cell)
Lymphocyte is a type of white blood cell that is the central effector of adaptive immunity, encompassing B cells that produce antibodies and T cells that carry out cellular immune responses, as well as natural killer cells that bridge innate and adaptive functions.
Lymphocytes arise in the bone marrow from common lymphoid progenitors; B cells complete maturation in the bone marrow while T cells migrate to the thymus, where positive and negative selection shape a self-tolerant, MHC-restricted repertoire. Each lymphocyte expresses a unique antigen receptor generated by somatic recombination of V, D, and J gene segments, a process capable of producing an estimated 10^18 distinct T cell receptor sequences in humans. Lymphocytes recirculate continuously through blood and lymphoid organs, surveying for antigens in lymph nodes, the spleen, and mucosal tissues.
After antigen encounter and activation, a small fraction of expanded lymphocytes persist as long-lived memory cells that respond more rapidly and vigorously upon re-exposure.
Lymphocytes make up roughly 20 to 40 percent of circulating white blood cells in healthy adults, but the vast majority of the body's lymphocytes at any given moment are not in the blood at all; they reside in lymphoid organs and tissues, with the gut-associated lymphoid tissue alone housing more lymphocytes than all other lymphoid organs combined.
Immune System Fun Facts →All lymphocytes look identical under a standard light microscope. B cells, T cells, and natural killer cells are morphologically indistinguishable in routine blood smears and can only be reliably told apart by surface marker staining with antibodies against proteins such as CD3, CD19, or CD56.
In Atlantic salmon (Salmo salar) vaccinated against infectious salmon anemia virus, memory B lymphocytes persist in the spleen and head kidney for at least 52 weeks after immunization. Upon re-exposure to the virus, these cells expand within three to four days and produce neutralizing antibodies at titers roughly 10-fold higher than those seen during the primary response.
Lymphokine
/ LIM-foh-kyn / · Latin lympha + Greek kinein (to move)
Lymphokine is a cytokine produced specifically by lymphocytes, particularly T cells, that mediates communication between immune cells by influencing the activity of other lymphocytes, macrophages, and non-immune cells.
The term lymphokine predates the broader cytokine nomenclature and originally referred to soluble factors produced by lymphocytes that could activate macrophages and promote inflammation without direct cell contact. IFN-gamma, produced by Th1 cells, is a classical lymphokine that activates macrophage killing of intracellular pathogens such as Mycobacterium tuberculosis by upregulating nitric oxide synthase and phagolysosome fusion. Modern immunology uses the term cytokine for all such molecules, but lymphokine remains in use historically and in some clinical contexts, particularly in older literature describing macrophage migration inhibitory factor and lymphotoxin.
The term was coined in the late 1960s by Dumonde and colleagues, who described non-antibody soluble mediators released by sensitized lymphocytes during antigen challenge.
Macrophage migration inhibitory factor (MIF), one of the first lymphokines described, was identified in 1966 by Barry Bloom and John David working independently, predating the discovery of most interleukins by more than a decade and establishing that lymphocytes could control other immune cells through secreted molecules rather than direct contact.
Immune System Fun Facts →Lymphokines are a separate category from cytokines. Lymphokines are a subset of cytokines defined by their cellular source; every lymphokine is a cytokine, but most cytokines are not lymphokines because they are produced by non-lymphocyte cells such as macrophages, fibroblasts, and endothelial cells.
When CD4 T cells in a tuberculin skin test encounter Mycobacterium tuberculosis antigens injected intradermally, they release lymphokines including IFN-gamma and lymphotoxin within 24 to 72 hours. These signals recruit and activate macrophages, producing the characteristic induration of 10 millimeters or more that indicates prior sensitization. This delayed-type hypersensitivity reaction was one of the first biological systems used to study lymphokine activity in vivo.