Lymphocyte | |
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Details | |
System | Immune system |
Function | White blood cell |
Identifiers | |
MeSH | D008214 |
TH | H2.00.04.1.02002 |
FMA | 84065 62863, 84065 |
Anatomical terms of microanatomy |
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. [1] Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), [2] [3] and innate lymphoid cells (ILCs; "innate T cell-like" cells involved in mucosal immunity and homeostasis), of which natural killer cells are an important subtype (which functions in cell-mediated, cytotoxic innate immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte" (with cyte meaning cell). [4] Lymphocytes make up between 18% and 42% of circulating white blood cells. [2]
The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. [2]
They can also be classified as small lymphocytes and large lymphocytes based on their size and appearance. [5] [6]
Lymphocytes can be identified by their large nucleus.
T cells (thymus cells) and B cells (bone marrow- or bursa-derived cells [lower-alpha 1] ) are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored maximally to eliminate specific pathogens or pathogen-infected cells. B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells , produce cytokines that direct the immune response, while other T cells, called cytotoxic T cells , produce toxic granules that contain powerful enzymes which induce the death of pathogen-infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and are able to mount a strong and rapid response if the same pathogen is detected again; this is known as acquired immunity.
NK cells are a part of the innate immune system and play a major role in defending the host from tumors and virally infected cells. [2] NK cells modulate the functions of other cells, including macrophages and T cells, [2] and distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called major histocompatibility complex (MHC) class I. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells. [1] They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I.
The X lymphocyte is a reported cell type expressing both a B-cell receptor and T-cell receptor and is hypothesized to be implicated in type 1 diabetes. [8] [9] Its existence as a cell type has been challenged by two studies. [10] [11] However, the authors of original article pointed to the fact that the two studies have detected X cells by imaging microscopy and FACS as described. [12] Additional studies are required to determine the nature and properties of X cells (also called dual expressers).
Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow. [13] This process is called haematopoiesis . [14] All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in a hierarchical fashion as well as in a more plastic fashion. The formation of lymphocytes is known as lymphopoiesis. In mammals, B cells mature in the bone marrow, which is at the core of most bones. [15] In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, [15] (B for bursa) and not from bone marrow as commonly believed. T cells migrate to the blood stream and mature in a distinct primary organ, called the thymus. Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (e.g. the spleen and lymph nodes) where they survey for invading pathogens and/or tumor cells.
The lymphocytes involved in adaptive immunity (i.e. B and T cells) differentiate further after exposure to an antigen; they form effector and memory lymphocytes. Effector lymphocytes function to eliminate the antigen, either by releasing antibodies (in the case of B cells), cytotoxic granules (cytotoxic T cells) or by signaling to other cells of the immune system (helper T cells). Memory T cells remain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure; they live weeks to several years, which is very long compared to other leukocytes.[ citation needed ]
Microscopically, in a Wright's stained peripheral blood smear, a normal lymphocyte has a large, dark-staining nucleus with little to no eosinophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of a red blood cell (about 7 μm in diameter). [13] Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or could exhibit a small clear zone to one side of the nucleus. Polyribosomes are a prominent feature in the lymphocytes and can be viewed with an electron microscope. The ribosomes are involved in protein synthesis, allowing the generation of large quantities of cytokines and immunoglobulins by these cells.
It is impossible to distinguish between T cells and B cells in a peripheral blood smear. [13] Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to determine the percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such as immunoglobulins or cluster of differentiation (CD) markers or that produce particular proteins (for example, cytokines using intracellular cytokine staining (ICCS)). In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like the ELISPOT or secretion assay techniques can be used. [1]
Class | Function | Proportion (median, 95% CI) | Phenotypic marker(s) |
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Natural killer cells | Lysis of virally infected cells and tumour cells | 7% (2–13%) | CD16 CD56 but not CD3 |
T helper cells | Release cytokines and growth factors that regulate other immune cells | 46% (28–59%) | TCRαβ, CD3 and CD4 |
Cytotoxic T cells | Lysis of virally infected cells, tumour cells and allografts | 19% (13–32%) | TCRαβ, CD3 and CD8 |
Gamma delta T cells | Immunoregulation and cytotoxicity | 5% (2–8%) | TCRγδ and CD3 |
B cells | Secretion of antibodies | 23% (18–47%) | MHC class II, CD19 and CD20 |
In the circulatory system, they move from lymph node to lymph node. [3] [17] This contrasts with macrophages, which are rather stationary in the nodes.
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A lymphocyte count is usually part of a peripheral complete blood cell count and is expressed as the percentage of lymphocytes to the total number of white blood cells counted.
A general increase in the number of lymphocytes is known as lymphocytosis, [18] whereas a decrease is known as lymphocytopenia.
An increase in lymphocyte concentration is usually a sign of a viral infection (in some rare case, leukemias are found through an abnormally raised lymphocyte count in an otherwise normal person). [18] [19] A high lymphocyte count with a low neutrophil count might be caused by lymphoma. Pertussis toxin (PTx) of Bordetella pertussis , formerly known as lymphocytosis-promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000 per μl in adults or over 8000 per μl in children. This is unique in that many bacterial infections illustrate neutrophil-predominance instead.
Lymphoproliferative disorders (LPD) encompass a diverse group of diseases marked by uncontrolled lymphocyte production, leading to issues like lymphocytosis, lymphadenopathy, and bone marrow infiltration. These disorders are common in immunocompromised individuals and involve abnormal proliferation of T and B cells, often resulting in immunodeficiency and immune system dysfunction. Various gene mutations, both iatrogenic and acquired, are implicated in LPD. One subtype, X-linked LPD, is linked to mutations in the X chromosome, predisposing individuals to natural killer cell LPD and T-cell LPD. Additionally, conditions like common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), and certain viral infections elevate the risk of LPD. Treatment methods, such as immunosuppressive drugs and tissue transplantation, can also increase susceptibility. LPDs encompass a wide array of disorders involving B-cell (e.g., chronic lymphocytic leukemia) and T-cell (e.g., Sezary syndrome) abnormalities, each presenting distinct challenges in diagnosis and management. [20]
A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma. [21]
One basis for low T cell lymphocytes occurs when the human immunodeficiency virus (HIV) infects and destroys T cells (specifically, the CD4 + subgroup of T lymphocytes, which become helper T cells). [22] Without the key defense that these T cells provide, the body becomes susceptible to opportunistic infections that otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4+ T cells in the patient's blood – HIV ultimately progresses to acquired immune deficiency syndrome (AIDS). The effects of other viruses or lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in the blood.
In some cancers, such as melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha".
Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. In addition, B cells present antigens and secrete cytokines. In mammals, including marsupials B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the B stands for bursa and not bone marrow, as commonly believed.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 × 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 × 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.
Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.
Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.
The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen.
Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear.
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.
Lymphopoiesis (lĭm'fō-poi-ē'sĭs) is the generation of lymphocytes, one of the five types of white blood cells (WBCs). It is more formally known as lymphoid hematopoiesis.
B1 cells are a sub-class of B cell lymphocytes that are involved in the humoral immune response. They are not part of the adaptive immune system, as they have no memory, but otherwise, B1 cells perform many of the same roles as other B cells: making antibodies against antigens and acting as antigen-presenting cells. These B1 cells are commonly found in peripheral sites, but less commonly found in the blood. These cells are involved in antibody response during an infection or vaccination.
Lutzner cells were discovered by Marvin A. Lutzner, Lucien-Marie Pautrier, and Albert Sézary. These cells are described as the smaller forms of Sézary cells, or Sézary-Lutzner cells, and the two variants are recognised as being morphologically different. Aggregates of these cells in mycosis fungoides are known as a Pautrier's microabscesses. They are a form of T-lymphocytes that have been mutated. This atypical form of T-lymphocytes contains T-cell receptors on the surface and is found in both the dermis and epidermis layers of the skin. Since Lutzner cells are a mutated form of T-lymphocytes, they develop in bone marrow and are transported to the thymus is order to mature. The production and maturation stages occur before the cell has developed a mutation. Lutzner cells can form cutaneous T-cell lymphoma, which is a form of skin cancer.
White blood cells, also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes: granulocytes, lymphocytes and monocytes.
Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.
A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.
Lymphocytes are recruited into the upper and lower airways during the early stages of a viral respiratory infection, and it is presumed that these cells help to limit the extent of infection and to clear virus-infected epithelial cells.
Lymphocytopenia may also be acquired, for example, in patients with HIV infection.