Lymphocyte

A lymphocyte is a type of agranular white blood cell in the vertebrate immune system.

Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells (NK cells). Small lymphocytes consist of T cells and B cells.

Types


The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells.

Natural killer cells
NK cells are a part of innate immune system and play a major role in defending the host from both tumors and virally infected cells. NK cells distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called MHC (major histocompatibility complex) 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. They were named "natural killer cells" because of the initial notion that they do not require prior activation in order to kill cells which are missing MHC class I.

T cells and B cells
T cells (thymus cells) and B cells (bone cells) 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 to maximally 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 pathogen is detected again.

Development


Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow. This process is called haematopoiesis. 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. B cells mature into B lymphocytes in the bone marrow, while T cells migrate to and mature in a distinct 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)in the 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 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 to a whole lifetime, which is very long compared to other leukocytes.

Characteristics


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 micrometres in diameter). 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. Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to specifically 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.

In the circulatory system they move from lymph node to lymph node. This contrasts with macrophages, which are rather stationary in the nodes.

Lymphocytes and disease
A lymphocyte count is usually part of a peripheral complete blood cell count and is expressed as percentage of lymphocytes to total white blood cells counted.

A general increase in the number of lymphocytes is known as lymphocytosis whereas a decrease is lymphocytopenia.

High
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).

Low
A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma.

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). 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. The effects of other viruses or lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in the blood.

Immunodeficiency
"A CD4 count of <200 × 10(6) cells/μL is very likely if the ED ALC is <950 × 10(6) cells/μL and less likely if the ALC is >1,700 × 10(6) cells/μL".

Tumor-Infiltrating Lymphocytes
In some cancers, e.g., melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.