A lymphocyte is a type of white blood cell that is part of the immune system. There are two main types of lymphocytes: B cells and T cells. The B cells produce antibodies that are used to attack invading bacteria, viruses, and toxins. The T cells destroy the body's own cells that have themselves been taken over by viruses or become cancerous.
Lymphocytes are cells that circulate in your blood that are part of the immune system. There are two main types lymphocytes: T cells and B cells. B cells produce antibody molecules that can latch on and destroy invading viruses or bacteria. T cells are direct fighters of foreign invaders and also produced cytokines, which are biological substances that help activate other parts of the immune system. One such part is called macrophages. These macrophages act to clean up the invaders and the dead tissue after an immune response.
T cells are a part of the immune system that focuses on specific foreign particles. Rather than generically attack any antigens, T cells circulate until they encounter their specific antigen. As such, T cells play a critical part in immunity to foreign substances.
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T cell function and use
The most common context of T cells is within infectious diseases, but they are used for other aspects of adaptive immunity too. This includes responses to allergens and tumors. They maintain immune homeostasis in humans over decades but can also be responsible for inflammatory or autoimmune diseases.
The role of T cells is slightly modified throughout the human lifetime. In infancy, naïve T cells are critical for developing immunity towards common pathogens or antigens. During this time, long-term reserves of memory T cells are established and can be maintained through adulthood.
In adulthood, when fewer novel antigens are encountered, they function mainly to maintain homeostasis and immunoregulation of repeat or chronically encountered antigens. There is also some focus on surveillance for tumors during this stage in life.
Later in life, the functionality of T cells decreases, which adds to the dysregulation of the immune system and associated pathologies.
T cell activation and mechanism
T cells originate in the bone marrow but are matured in the thymus. However, they are not activated until they find their specific antigen. They bind to this antigen on the surface of antigen-presenting cells (APCs). Typically, several types of T cells are involved in this, mainly CD4 helper T cells and CD8 cytotoxic T cells, and together they form the MHC complex.
The activation of T cells is not always as binding to the MHC. Both helper T cells and cytotoxic T cells (two of the types of T cells) need secondary signals to become fully activated and be effective towards the threat. These are provided by several molecules, such as CD28 which activate helper T cells.
In general, there are three types of T cells: cytotoxic, helper, and regulatory. All of these must react to foreign antigens strongly to be effective for immunity. T cells with a strong reaction are also given survival signals by several molecules, such as ICOS and OX40. These are only expressed on the T cell surface following binding with the antigen, to ensure it is only active after response to a pathogen.
After activation, communication occurs in the form of cytokines. The cytokines decide what form of responder the cells turn into. Helper T cells become Th1, Th2, or IL-17 types. Each of these types has its own role in the continued development of further immune responses.
T cells and COVID-19
Because the clearing of a virus depends on an effective immune response, T cells have again come into focus following the COVID-19 pandemic. Therefore, boosting the function and quantity of T cells is important in COVID-19 patients to ensure recovery.
Initial studies indicated that there was a decrease in T cells in patients with COVID-19. This also related to the severity of the disease, with 70.56% of non-ICU patients having decreased levels of total T cells, CD4 and CD8 T cells. ICU patients showed an even higher proportion, with 95% of patients showing a decrease in total T cells and CD4 T cells. 100% of ICU patients also had decreased CD8 T cell levels.
However, the mechanism of this is still uncertain. There is some hypothesis that this is an artifact of the age groups commonly hospitalized for COVID-19 – people over the age of 60, who are disproportionately hospitalized, can be experiencing reduced T cell levels due to higher levels of cytokines such as TNF-α and IL-10. Dysregulated cytokine levels can be central in cases of chronic inflammation.
There is also some evidence that deleterious progression of COVID can be prevented in patients with low T cell counts. Because of the suspected role of cytokines, blocking these can potentially be an effective strategy to prevent T cell exhaustion and allow for more positive COVID-19 outcomes.
Some cytokines, or some of these such as IL-10, are inhibitory cytokines and as such, they can prevent T cell proliferation. This means their elevated presence in COVID-19 patients can be central to the observed reduced levels of T cells and can be linked to poorer COVID-19 outcomes.
However, some recent research indicates that, in general, patients who suffer more severe disease later have a stronger long-term T cell response and longer-term immunity. Research still needs to be conducted into T cell response in COVID-19, particularly in terms of long-term immunity.
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Last updated Mar 30, 2021
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T cell and B cell lymphocytes work together to recognize foreign substances called antigens. As the primary agents responsible for adaptive immunity, T cells and B cells are sometimes called the “special ops” of the immune system. Inherent structural features of the B and T cell receptors are what provide antigen binding specificity.
Lymphocytes originate from a lymphoid progenitor cell in a process called hematopoiesis. In hematopoiesis, stem cells within bone marrow differentiate into myeloid progenitors or lymphoid progenitors, which then specialize into about a dozen different cell types including blood cells, platelets, and macrophages—which are all myeloid in origin—and lymphocytes.
Lymphocytes can be further differentiated into B cells, T cells, and natural killer cells. While natural killer cells recognize general signals of immune stress such as inflammation, B and T cells recognize foreign antigens specifically via hypervariable B cell and T cell receptors (BCRs and TCRs). B cells recognize free, unprocessed antigens. T cells recognize antigens within a complex of cell surface proteins called the major histocompatibility complex (MHC) on the surface of antigen-presenting cells (also called accessory cells).
The proper function of B cells and T cells is essential to protect the body from foreign invasion by viruses or bacteria. This proper function is contingent on T and B cell structure, as it dictates their activation and downstream function. When these systems go haywire, the body is left susceptible to diseases and cancer. In the case of auto-immune disease, the immune system itself can even become a detriment. By studying the unique composition of diverse B cells and T cells on both a macro (large population) and micro (individual) level, we can gain insights into how to treat or prevent diseases.
For case studies of BCR and TCR research, see our page on sequencing the immune repertoire
Introduction to Adaptive Immunity
Our bodies protect us from foreign invasion through two main defense systems: innate immunity and adaptive immunity. Innate immunity is a general defense mechanism that works non-selectively to keep out potential threats. Physical barriers like skin and chemical responses like inflammation both constitute innate immunity. The defining feature of innate immunity is that the response is more or less the same regardless of invasion type.
Adaptive immunity, on the other hand, is a specific, acquired response to particular invaders. In adaptive immunity, toxins or foreign substances, called antigens, are recognized specifically via molecular signatures. The full breadth of threats that our adaptive immune system can recognize changes overtime as we are exposed to new antigens.
Adaptive immunity depends on the diversity of B cell and T cell receptors. The individual components of BCRs and TCRs achieve diversity through random recombination of the genes that encode them. In BCRs, this diversity is further expanded via somatic hypermutation.
For more information, see our page on diversity and differentiation in the adaptive immune System
When a BCR or TCR recognizes a foreign antigen, the cells housing that receptor proliferate in a process called clonal expansion. Most of these newly made cells will die off after the antigen is destroyed, but some of them are destined to live on as memory B or T cells. This new population of memory cells allows for a faster response when the same antigen is encountered again. Vaccines work by priming the adaptive immune system to respond to a particular pathogen by introducing antigens in the absence of the disease. The lymphocytes that recognize those antigens proliferate and create memory cells, so that if the body is challenged by the actual disease in the future, the adaptive immune system is ready to respond quickly.
The structures of both T and B cell receptors are defined by three regions: the variable, constant and transmembrane regions. Precise T cell and B cell structure is important for activation. In both BCRs and TCRs it is the variable region that constitutes the antigen-binding site.
T cell structure and function
T cell receptors are made up of two polypeptide chains that together compose one antigen binding region. Approximately 95% of TCRs are composed of an alpha and a beta chain, while the remaining 5% of TCRs are made up of gamma and delta chains. The T cell receptor structure is maintained by a disulfide bond linking the two chains together. Complementary determining regions (CDRs) are key structural features that lie within the variable region and provide the specificity in antigen binding.
There are multiple types of T cells, and each has a specialized function. Cytotoxic T cells, also known as Killer T cells, generally target cancer, virally infected, or damaged cells. Killer T cells respond to antigens by releasing cytotoxic granules that lead to apoptosis. Helper T cells help recruit B cells and other cells involved in the immune response by releasing cytokines. Memory T cells have an extended lifetime and help to recognize antigens to which they were previously exposed.
B cell structure and function
B cell receptors are made up of four peptides – two light chains and two heavy chains – that comprise two antigen-binding regions. Light chains are classified as either kappa or lambda, while the heavy chains can be IgG, IgA, IgM, IgD, or IgE isotypes.
B cells can be activated in two ways: T cell-dependent activation or T cell-independent activation. During T cell-dependent activation, B cells absorb the antigen and then present pieces of the antigen on their surface via a major histocompatibility complex (MHC). Helper T cells can then recognize those antigens via the MHC and activate the B cells. For T cell-independent activation to take place, the B cell must both encounter an antigen and receive a “danger signal,” which is a signal that an attack is occurring.
Activated B cells can then either become effector B cells or memory B cells. Effector B cells, also called plasma cells, produce antibodies. Antibodies work as tags or alarms to target invading agents for destruction by other immune agents like macrophages. Memory B cells, like memory T cells, help the immune system respond more quickly to future invasions by the same agent.
Lymphocyte-related diseases and treatment
When something goes wrong with the adaptive immune system, disease can result. Auto-immune diseases occur when B and T cells falsely recognize molecules that are not foreign as a threat. Lymphocytes are also involved in allergic reaction responses. In HIV infection, B cells and T cells become exhausted and no longer function properly. Finally, like any cell, B and T cells can mutate and divide uncontrollably, resulting in lymphoma. An improved understanding of the lymphocyte landscape within populations or individuals can help lead to improved tests and treatments for these diseases.
T cell and B cell associated therapies are an important component of cancer treatment. For example, some cancer cells produce molecules that can deactivate T cells. These cancer cells hijack the natural systems that evolved to turn T cells off when an infection has cleared. Checkpoint inhibiting drugs prevent this mechanism so that T cells will not be prematurely inhibited by cancer cells.
An exploratory but promising type of treatment called CAR-T cell therapy uses T cells to fight B cell lymphomas. In CAR-T therapy, a patient’s T cells are extracted, modified so that they recognize B cell surface proteins as antigens, and reintroduced. The modified T cells destroy cancerous as well as healthy B cells. Before long, the modified T cells are circulated out of the body, and the supply of normal lymphocytes is regenerated.
For more examples relating TCR and BCR research to medical applications, see our page on the immune repertoire and adaptome.