Lymphocytes – functions, structure, examination, norms. How to raise or lower the level of lymphocytes? [EXPLAINED]

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The immune system is one of the most important systems in the body of all of us. If it does not function properly, other systems begin to fail and individual internal organs do not function properly. That is why regular blood tests are so important. The concentration of individual blood components allows the assessment of the immune system’s work. One of these ingredients is lymphocytes. What is their role and what does their blood concentration show?

Acquired immunity, as the name suggests, is acquired over time. According to experts, we do not fully reach it until we are 20 years old. Only after 20 years, our immune system has an immune memory built on the basis of past diseases and infections. After each infection caused by a virus or bacteria, the so-called immune memory cells. When the same microorganism attacks us again, the created cells will capture it and render it harmless.

In turn, innate immunity are the cells and tissues that nature has provided us with. From birth, they are designed to protect us against dangerous external factors, such as bacteria, viruses and fungi.

To get to our body, microorganisms must overcome the first barrier, which is the skin and mucous membranes. This is not an easy task, because the acidic pH of the skin, which is deadly for viruses and fungi, is an obstacle. Another obstacle are bactericidal substances secreted by our body, such as urine, sweat or tears. The mucous membranes and the secretions they produce are another barrier designed to keep fungi, bacteria and viruses outside the body.

However, if the microorganisms can cope with the first barrier and get inside the body, phagocytes are activated, i.e. feeding cells. Accumulated in the lymph nodes, they begin to secrete substances that attract enemies. They then surround the intruder and begin to absorb it, making it harmless to the body. It is worth knowing that phagocytes are also responsible for the production of substances called pyrogens, responsible for raising the temperature of our body. Also, leading to the development of fever is to get rid of viruses and bacteria from our body.

If the second protective barrier failed to cope with germs, and these have become established in our body for good, lymphocytes enter the action, which, after recognizing the microorganism, transform into antibodies directed directly at the intruder. What else do lymphocytes do?

Also read: 10 ways to strengthen immunity

There are three main groups of lymphocytes:

1. T (thymic-dependent) lymphocytes – constitute the largest group of lymphocytes, and their task is the cellular immune response (they destroy antigens);
2. B (myeloid-dependent) lymphocytes that produce immune antibodies;
3. NK cells, which exert cytotoxic activity by destroying viral and cancer cells).

The role of lymphocytes in the body is therefore to recognize and eliminate antigens. When lymphocytes destroy cells containing foreign antigens (e.g. viruses) – this reaction is beneficial for the body and protects against disease development. However, it is disadvantageous when autoimmune diseases or transplant rejection are involved.

T lymphocytes are involved in cellular immunity, while B lymphocytes are primarily responsible for humoral (antibody-related) immunity. The function of T cells and B cells is to recognize certain “non-specific” antigens by a process known as antigen presentation. Once identified, the invader cells generate specific responses that are maximally tailored to eliminate specific pathogens or pathogen-infected cells. B lymphocytes respond to pathogens by producing large amounts of antibodies which then neutralize foreign objects such as bacteria and viruses.

In response to pathogens, certain T lymphocytes, called Th lymphocytes, produce cytokines that drive the immune response, while other T lymphocytes, called cytotoxic T lymphocytes (Tc lymphocytes), produce toxic granules containing potent enzymes that induce the death of cells infected with pathogens.

NK cells, in turn, modulate the functions of other cells, including macrophages and T lymphocytes, and distinguish infected cells and tumors from normal and uninfected cells by recognizing changes in a molecule called MHC (major histocompatibility complex). 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 changed cells.

Interestingly, when we are talking about lymphocytes, it is also worth mentioning the hypothetical fourth group of lymphocytes. It is about the so-called X lymphocytes

X-lymphocyte is a reported cell type expressing both the B-cell receptor and the T-cell receptor and is presumed to be associated with type 1 diabetes. Its existence as a cell type has been questioned in two studies (first published in the journal Cytometry Part A in 2020 . and two years later, published in the Cell journal). However, the authors of the original paper (also published in the journal Cell in 2022) noted that these two studies detected X lymphocytes using imaging microscopy and FACS. Of course, additional research is required to determine the nature and properties of X lymphocytes (also known as X cells).

Also read: Our T cells can kill cancer

Development of lymphocytes

Human stem cells differentiate into several types of blood cells in the bone marrow. This process is called hematopoiesis. During this process, all lymphocytes derive from a common lymphoid ancestor before differentiating into distinct types of lymphocytes. Lymphocyte differentiation follows different pathways in a hierarchical and also more plastic way. The formation of lymphocytes is known as lymphopoiesis. In mammals, B cells mature in the bone marrow, which is the core of most bones. T cells migrate into the bloodstream and mature in a separate primary organ called the thymus. After maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (e.g. the spleen and lymph nodes) where they check for invasion of pathogens and / or cancer cells.

Lymphocytes involved in acquired immunity (ie, B and T lymphocytes) further differentiate upon antigen exposure; they form effector and memory lymphocytes. The role of effector lymphocytes is to eliminate the antigen by releasing antibodies (in the case of B lymphocytes), cytolytic grains (Tc lymphocytes) or by transmitting signals to other cells of the immune system (Th lymphocytes). Memory lymphocytes remain in peripheral tissues and circulation for an extended period of time, ready to respond to the same antigen in the event of future exposure; they live from weeks to several years, which is a very long period compared to other leukocytes.

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Structure of lymphocytes

Microscopically, in a Wright stained peripheral blood smear, a normal lymphocyte has a large, dark colored nucleus with little or no eosinophilic cytoplasm. Normally, a thick, dense lymphocyte nucleus is approximately the size of a red blood cell (approximately 7 µm in diameter). Some lymphocytes show a distinct perinuclear zone (or halo) around the nucleus or may show a small distinct zone on one side of the nucleus. Polyribosomes are an essential feature of lymphocytes and can be viewed under an electron microscope. Ribosomes are involved in the synthesis of proteins, enabling these cells to produce large amounts of cytokines and immunoglobulins.

T cells cannot be distinguished from B cells on a peripheral blood smear. Typically, flow cytometry is applied to a specific number of lymphocyte populations. 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 produce specific proteins such as cytokines using intracellular cytokine staining (ICSS). .intracellular cytokine staining). Other scientific techniques such as ELISpot can be used to test the function of lymphocytes due to the proteins they produce.

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Lymphocytes – norms

The lymphocyte test involves taking a blood sample from the patient from a vein in the arm. However, it should be taken into account that the result of the analysis is influenced by various factors, such as taking certain medications, supplements or diet. Therefore, a few days before the test, physical activity and food should not be changed.

Before performing the test, you should also inform your doctor about the medications and supplements you are taking, because they can significantly affect the test result and cause increased bleeding after the test. In addition, you should also report if you are allergic to latex and any discomfort that has ever appeared before blood sampling.

You should go to the test on an empty stomach.

In order to measure lymphocytes, make an appointment for basic blood tests, which take into account the morphology, but also additional parameters (in this case, cholesterol and sugar). The analysis of the results will allow for an overall assessment of the state of health

Normal lymphocyte counts vary with age, and the percentages should be within the following range:

1. children up to 6 days: 26-36%;
2. children 7-13 days: 36-46%;
3. children 14-30 days: 43-53%;
4. children 1-11 months: 45-75%;
5. children from 1 to 3 years: 50-70%;
6. children 4-5 years: 40-60%;
7. children 6-7 years: 32-52%;
8. children 8-15 years: 28-48%;
9. youth 16-19 years: 25-45%;
10. adults: 18-44% (some sources give 15-40% as correct).

Do you need interpretation of test results? Are you worried about your symptoms? Contact your doctor. Make an online teleconsultation with your family doctor at haloDoctor.pl to get answers to your questions.

Lymphocytes below normal

Percentage of lymphocytes below 15 is a cause for concern and denotes a weakening of the immune system. There are various reasons for this condition. Doctors call abnormally low lymphocyte counts lymphocytopenia. In adults, it is usually less than 1000 lymphocytes in 1 µl of blood.

Low levels of lymphocytes are associated with some hereditary conditions, such as Wiskott-Aldrich syndrome or DiGeorge’s syndrome, as well as aplastic anemia.

Other possible causes are viral diseases, such as AIDS and hepatitis, or autoimmune diseases – multiple sclerosis, lupus, rheumatoid arthritis. To rule out the suspicion of autoimmune diseases, make an appointment with a neurologist. The decreased level of lymphocytes is also a typical symptom of some cancers, especially those related to the haematopoietic system. Very low levels of lymphocytes occur in leukemia and lymphoma. The cause of lymphopenia, i.e. a low level of lymphocytes, does not have to be a serious disease, however. This condition also occurs as a result of taking certain medications, during periods of increased stress or as a result of intense exercise.

Lymphocyte test results, as well as any other test results, should always be discussed with your doctor. Make an e-consultation with an internist online to get advice on health matters without leaving your home.

See also: What do lymphocytes below normal mean?

Treating the underlying disease may increase lymphocyte counts in other cases where the condition is evident. For example, doctors may prescribe antibiotics to treat a bacterial infection that can cause abnormally low levels of lymphocytes.

Some diseases may require long-term treatment to increase the number of lymphocytes. For example, people with lupus may require a combination of drugs to manage their disease. Disease management can increase the number of lymphocytes to normal levels.

Lymphocytes above normal

Above normal lymphocyte concentration may also be a symptom of the disease. High levels of lymphocytes may be a sign of lymphocytosis, which may indicate a more serious condition. Doctors usually call lymphocytosis more than 4000 lymphocytes per 1 µL of blood in adults. However, this threshold may vary between laboratories and people of different ages. This condition can be a consequence of:

1. viral infection such as HIV;
2. a bacterial infection such as Bartonella henselae;
3. a parasitic infection such as Toxoplasmosis;
4. a tumor of the hematopoietic or lymphatic system;
5. autoimmune disorders.

The symptoms of an elevated lymphocyte count depend on the underlying disease that contributed to the condition. Possible diseases include:

1. lymphocytic leukemia, AIDS (or HIV carrier);
2. infectious mononucleosis;
3. cancer, such as non-Hodgkin’s lymphoma;
4. multiple myeloma;
5. tuberculosis;
6. systemic vasculitis;
7. whooping cough.

High levels of lymphocytes can also be caused by stress, and may also be the body’s response to a drug.

Both increased lymphocytes in a child and an adult are an indication for further diagnosis (e.g. blood tests or imaging tests) and treatment. The sooner therapy is started, the greater the chances of recovery.

Find out more about chronic lymphocytic leukemia

For example, the Epstein-Barr virus (EPV) is one of the most common causes of abnormally high levels of lymphocytes. The virus can cause mononucleosis, and doctors may recommend over-the-counter pain medications and rest until symptoms have cleared.

Other possible causes may require appropriate treatment, as directed by your doctor. For example, some people may experience high levels of lymphocytes as a result of cancer. Doctors may recommend a combination of approaches to treating cancer, such as chemotherapy and surgery.

See also: What do elevated lymphocytes mean?

The level of lymphocytes in pregnancy

The norm of lymphocytes during pregnancy is 20–45% (or 1,5–4,0 * 10 ^ 9 / l). However, it should be remembered that the lower and upper limits may slightly differ depending on the reference values ​​adopted in a given medical laboratory.

In the case of depressed lymphocytes during pregnancy, it is characteristic of the first and second trimesters, so you should not always worry about it. However, this does not change the fact that the test results should always be assessed by a doctor. Low lymphocytes during pregnancy may indicate that the immune system is weakened. Lymphocyte depletion during pregnancy can be caused by stress, hematological diseases, malnutrition, infections, endocrine diseases, or cancer.

Conversely, elevated lymphocytes during pregnancy are usually caused by the physiological changes that occur in a woman’s body after conception (increase in white blood cells). Unfortunately, sometimes elevated levels of lymphocytes can also result from pathological processes that require treatment. Pregnant women are more prone to various types of infections, mainly from the genitourinary system. Higher than normal levels of lymphocytes may be due to a low-grade fever or a fever. It is very important to establish the cause of the abnormal lymphocyte levels and implement appropriate therapy, as this situation may endanger the developing baby. Among the reasons for the high level of lymphocytes there are also: infections of the oral cavity and periodontium, allergies, poisoning, toxoplasmosis, neoplastic diseases (especially leukemia).

Abnormal levels of lymphocytes in pregnancy do not always need to be treated. Everything is always decided by a specialist who must take into account blood count parameters, results of additional tests and clinical symptoms. The doctor focuses on the causes that caused the abnormalities, always trying to adjust the method of treatment so as not to harm the developing child.