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What Do Lymphocyte Values Explain?

Lymphocyte levels are part of a complete blood count with differential. The range of "normal" lymphocytes is shown here.

Lymphocytes play the key role in adaptive and innate immunity. They are particularly activated in response to viruses and cancer.

  • Many disorders decrease the number of lymphocytes in the blood but viral infection is the most common cause. Other causes are bacteria, fungi, and parasites.

  • A decrease in lymphocyte level in the blood (<1500 cells/microliter) renders you vulnerable to chronic bacterial infections. This condition is called lymphopenia or lymphocytopenia. Lymphopenia may be due to:

1. Increased trafficking of lymphocytes from the blood to lymphoid tissue and decreased egress of lymphocytes from lymphoid tissue to blood;

2. Infectious agents, chemotherapy, and radiation therapy;

3. Loss of lymphocyte-rich lymphatic fluid and disruption of the normal lymphoid tissue architecture (lymphoma, for example); Immunodeficiency syndromes. Diseases of Rickettsia and Ehrlichia bacteria, EBV and other viral infections, and SARS-CoV-2 lead to lymphocytopenia.

  • Lymphocytosis is an elevation in lymphocyte levels in the blood (>2000 cells/microliter). Causes of elevated lymphocytes include infections, just like in lymphopenia. Thus, any level of lymphocytes outside the range 1500 - 2000 infers some infectious process.


Lymphocyte Review

There are about 2 × 10 to the 12th power (aka - a ton) of lymphocytes in the human body, making the immune system comparable in cell mass to the liver or brain. Despite their abundance, their central role in adaptive immunity was not demonstrated until the late 1950s.

The crucial experiments were performed in mice and rats that were heavily irradiated to kill most of their white blood cells, including lymphocytes. This treatment makes the animals unable to mount adaptive immune responses. Then, it was possible to determine which cells reversed the deficiency by transferring various types of cells into the animals. Only lymphocytes restored the adaptive immune responses of irradiated animals, indicating that lymphocytes are required for these responses.

Most lymphocytes die in the central lymphoid organ soon after they develop, without ever functioning. Others, however, mature and migrate via the blood to the peripheral (secondary) lymphoid organs—mainly, the lymph nodes, spleen, and epithelium-associated lymphoid tissues in the gastrointestinal tract, respiratory tract, and skin. It is in the peripheral lymphoid organs that T cells and B cells react with foreign antigens.


In some people—around ~15%—lymphocytes go up when I would have expected them to go down. How can this be explained or anticipated? This may be a difficult question to answer. However, any deviation from the properly derived reference ranges infers some infectious process. White blood cells essentially only move from the normal values with infections.

Hopefully, this narrative will provide some insights into the behavior of lymphocytes.

Summary: Lymphocytes are partitioned between the lymphatic and vascular systems, which may explain the higher or lower counts of lymphocytes in the blood test.

Definition: Antigen is an infectious agent recognized by the immune system.

Pathogens generally enter the body through an epithelial surface, usually through the skin, gut, or respiratory tract. How do the microbial antigens travel from these entry points to a peripheral lymphoid organ, such as a lymph node or the spleen, where lymphocytes are activated?

The route and destination depend on the site of entry.

  • Antigens that enter through the skin or respiratory tract are carried via the lymph to local lymph nodes;

  • those that enter through the gut end up in gut-associated peripheral lymphoid organs such as Peyer's patches and

  • those that enter the blood are filtered out in the spleen.

Some lymphocytes can recognize a particular microbial antigen in a peripheral lymph organ, but they are only a tiny fraction of the total lymphocyte population. How do these rare cells find an antigen-presenting cell displaying their antigen? The answer is that they continuously circulate between the lymph and blood until they encounter their antigen.

In a lymph node, for example, lymphocytes continually leave the bloodstream by squeezing out between specialized endothelial cells lining small veins called postcapillary venules. (Remember, we measure lymphocytes in the blood). After percolating through the node, they accumulate in small lymphatic vessels that leave the node and connect with other lymphatic vessels that pass through other lymph nodes downstream.

Passing into larger and larger vessels, the lymphocytes eventually enter the main lymphatic vessel (the thoracic duct), which carries them back into the blood. This continuous recirculation between the blood and lymph ends only if a lymphocyte encounters its specific antigen on the surface of an antigen-presenting cell in a peripheral lymphoid organ.

Now, the lymphocyte is retained in the peripheral lymphoid organ, where it proliferates and differentiates into effector cells. Some of the effector T cells then leave the organ via the lymph and migrate through the blood to the site of infection.


High Lymphocyte Counts in the Blood.

Lymphocytosis occurs most commonly after viral infections (e.g., cytomegalovirus, mumps, varicella, influenza, rubella, etc.), lymphoid leukemias and lymphomas, and smoking. It is rarely observed in bacterial infections, with the exception of Bordetella pertussis infection.

It's possible to have a higher-than-usual lymphocyte count but few, if any, symptoms.

However, the higher count might result from something more serious, such as a blood cancer or a chronic infection. More tests can show if the lymphocyte count is a cause for worry.

A high lymphocyte count can point to:

  • Infection, including bacterial, viral, or other type of infection.

  • Cancer of the blood or lymphatic system.

Causes of lymphocytosis include:

  • Acute lymphocytic leukemia

  • Babesiosis

  • Brucellosis

  • Cat-scratch disease

  • Chronic lymphocytic leukemia

  • Cytomegalovirus (CMV) infection

  • Hepatitis A

  • Hepatitis B

  • Hepatitis C


  • Hypothyroidism (underactive thyroid)

  • Lymphoma

  • Mononucleosis

  • Severe medical stress, such as from trauma

  • Smoking

  • Splenectomy

  • Syphilis

  • Toxoplasmosis

  • Tuberculosis

  • Whooping cough



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