Basophil – Definition, Mechanism, Structure, Functions

Basophils are an immunological cell type that release enzyme-containing granules during allergic responses and asthma crises. Basophil is a type of white blood cell that, together with neutrophils and eosinophils, belongs to the granulocytes category.

They contain several chemicals, including histamine and heparin. As part of the body’s immune response, basophils degranulate (split open) to release these chemicals after an allergic reaction. These cells serve a variety of activities to safeguard our bodies, and there are a number of diagnostic tests available to determine the extent of any damage or disease we may be experiencing.

What are Basophils?

• Basophils are a type of white blood cell that play a crucial role in the immune response against parasites and are involved in allergic reactions. Although they make up only a small percentage of circulating blood cells (about 0.5%), their numbers can rapidly increase in response to inflammatory signals.
• These nonphagocytic granulocytes are produced in the bone marrow from granulocyte-monocyte progenitors and then populate the peripheral blood as mature cells. Basophils share developmental similarities with mast cells, as both express high-affinity receptors for IgE and release similar mediators in response to IgE binding.
• Distinguishing basophils from other cell types can be done using specific markers such as ckit–FcεRI+, CD11b+, and IL-3Rhi. Additionally, a basophil activation test has been developed to detect allergic reactions to substances like drugs, food, and venom in patients.
• Basophils have a short lifespan and are relatively scarce, which has made studying their functions and responses challenging. However, they are considered circulating innate cells that contribute to the Th2 immune response and facilitate the transmigration of other leukocytes into inflamed tissues by inducing microvascular permeability.
• In terms of their role in allergic reactions, basophils are responsible for the release of compounds such as histamine and serotonin, which induce inflammation, as well as heparin, which prevents blood clotting. However, the amount of these compounds produced by basophils is less than that found in mast cell granules. It is important to note that mast cells and basophils were once thought to be the same type of cell, but they are now known to be distinct.
• Overall, basophils are critical components of the immune system, involved in both the immune response against parasites and the development of allergic diseases. Their unique characteristics and functions contribute to the complex network of cells and molecules that orchestrate immune reactions in the body.

Definition of Basophils

Basophils are a type of white blood cell that are involved in immune responses against parasites and play a role in allergic reactions. They are nonphagocytic granulocytes and represent a small percentage of circulating blood cells. Basophils release compounds such as histamine and heparin, contributing to inflammation and preventing blood clotting.

Structure of Basophils

• Basophils are the smallest granulocytes, typically measuring between 10-14 µm in diameter. They have a polylobed nucleus and prominent cytoplasmic granules that exhibit bright metachromatic staining. While most basophils are rounded, some may have elongated, narrow uropods or tails.
• The nucleus of a basophil contains condensed chromatin, but lacks a nucleolus. The cytoplasm contains various organelles, including mitochondria, vesicles, glycogen, and granules. The mature granules are typically round to angular, membrane-bound structures ranging in size up to 1.2 µm. These granules consist of dense particles within a less dense matrix and may have a complex membrane structure.
• Basophils possess a complex vesicular system in their cytoplasm, which is involved in the process of degranulation upon stimulation. This means that the granules release their contents in response to specific triggers. The structure of basophils closely resembles that of mast cells, but they can be differentiated based on their glycogen content and the absence of plasmalemmal ridges and folds found in mast cells.
• The cytoplasmic granules of basophils contain histamine, a chemical that plays a role in inflammatory reactions when released upon stimulation. The granules are large enough to obscure the cell nucleus when stained, but the nucleus becomes visible when unstained. Basophils and mast cells both store histamine and share similar functions, but they arise from different branches of hematopoiesis. Mast cells are typically found in connective tissue rather than circulating in the bloodstream like basophils.
• Basophils, like other granulocytes, can be recruited from the blood into tissues as needed for immune responses or inflammatory reactions. Their distinctive structure and granule composition contribute to their specialized functions within the immune system.

Development of Basophils

• Basophils undergo a specific developmental process within the bone marrow before entering the bloodstream. They share a common progenitor cell with eosinophils and neutrophils. The differentiation of basophils from other cell types is not fully understood, but the emergence of interleukin-3 (IL-3) appears to be involved in this process.
• IL-3 plays a role in promoting the development of precursor cells in the bone marrow. While mast cells remain primarily in tissues, basophils have the ability to circulate in the bloodstream and can be recruited to sites of inflammation or immune response. However, under normal conditions, basophils are not commonly found in normal tissue.
• Basophils originate from hematopoietic stem cells influenced by myeloid progenitors. The development of basophils proceeds in the bone marrow or spleen as pre-basophil/mast cell progenitors. Once fully developed, basophils are released into the bloodstream, where they await stimulation by allergens or other stimuli.
• Basophils can be activated by various factors, including immunoglobulins (such as IgE antibodies), cytokines, growth factors, bacteria or bacterial subparticles, parasites, viruses, and allergens. When stimulated, basophils can undergo degranulation, releasing their cytoplasmic granules and the substances contained within them, such as histamine and other mediators involved in immune responses and inflammation.
• The activation of basophils is a crucial step in their immune function, as it allows them to respond to specific triggers and participate in the body’s defense against pathogens, parasites, and allergic reactions. Understanding the development and activation of basophils helps shed light on their role in immune processes and provides insights into potential therapeutic targets for conditions involving basophil dysregulation.

How do Basophils work against pathogens? (Immunity)

Basophils play a crucial role in the immune response against pathogens, particularly during parasitic infections and allergic reactions. Here is how basophils work against pathogens:

1. Basophil Formation: Basophils are formed from the granulocyte-monocyte progenitor cells in the bone marrow. These precursor cells differentiate into basophils under the influence of the transcription factor C/EBPα. Once fully differentiated, basophils are released into the peripheral blood.
2. Basophil Increase: Under normal conditions, the number of basophils in the blood remains relatively stable. However, in response to parasitic infections or allergies, the number of basophils increases. The exact stimuli responsible for basophil development during parasitic infections are not fully understood, but hematopoietic cytokines like interleukin-3 (IL-3) are believed to play a significant role. Additionally, parasite-associated molecules such as proteases, glycoproteins, or structural components like chitin can also act as stimuli for basophil differentiation.
3. Activation of Basophils: Basophils, similar to mast cells, are activated by the cross-linkage between the surface receptor for immunoglobulin E (IgE), called FcεRI, and IgE antibodies present in the blood. When IgE binds to basophils, it triggers an activation signal.
4. Release of Mediators: Upon activation, basophils rapidly release intracellular mediators such as histamine and leukotrienes. These compounds contribute to increased secretion of cytokines like interleukin-4 (IL-4) by basophils. Basophils can be activated through IL-4-independent pathways involving IL-3 as well.
5. Induction of Th2 Response: Activated basophils produce a substantial amount of IL-4, which can even exceed the amount produced by T cells. IL-4 released by basophils plays a critical role in inducing the activation of parasite-specific naïve T cells, promoting their differentiation into Th2-type effector T cells. Th2 cells are crucial for orchestrating the immune response against parasites.

By producing and releasing mediators and cytokines, basophils actively contribute to the immune response against pathogens, particularly in parasitic infections. Their ability to induce Th2 responses and communicate with other immune cells helps in mounting an effective defense against pathogens and coordinating the overall immune response.

Microscopic (histologic) description

Microscopic (histologic) description of basophils reveals distinct characteristics at various stages of development. Here is a description of basophilic cells at different stages:

1. Basophilic Myeloblast: Basophilic myeloblasts are difficult to differentiate from other granulocyte blasts under a microscope. They are large, spherical cells with basophilic cytoplasm and lack granules. The nucleus-to-cytoplasm (N/C) ratio is high at around 80%. The chromatin in the nucleus appears scattered, including the presence of a nucleolus.
2. Basophilic Promyelocyte: Basophilic promyelocytes serve as developmental intermediates between basophilic myeloblasts and myelocytes. These circular cells have undifferentiated cytoplasmic granules. The chromatin in the nucleus shows slight clustering, and a nucleolus may be present.
3. Basophilic Myelocyte: Basophilic myelocytes are often larger than neutrophilic granules. They have a moderate N/C ratio of around 50%. The chromatin in the nucleus is moderately compacted, and there is no distinct nucleolus.
4. Basophilic Metamyelocyte: Basophilic metamyelocytes are oval-shaped cells with abundant pale cytoplasm. They possess large and rather uniform specific granules. The N/C ratio decreases to approximately 40%. The nucleus is small, indented, and has condensed chromatin, while the nucleolus is absent.
5. Basophil: Basophils are smaller than normal white blood cells, typically measuring 10-15 microns in diameter. The cytoplasm appears pale blue but is frequently obscured by purple-blue granules, which contain substances such as heparin and histamine. The N/C ratio decreases further to around 20%. The nucleus of basophils is often unsegmented or bilobed, with coarse chromatin.

Microscopically, basophils can be identified by their characteristic cytoplasmic granules, metachromatic staining (reddish purple) with dyes like Toluidine blue and Alcian blue, and specific nuclear features. These microscopic descriptions aid in distinguishing and identifying basophils within a histologic sample, providing insights into their maturation and cellular morphology.

Action of Basophils

• Basophils contribute to the activation of inflammatory reactions.
• Inflammation is the body’s natural response to anything that could be harmful.
• It is the body’s way of instructing the immune system to mend and restore damaged tissues while defending against foreign invaders.
• Histamine and heparin are among the chemicals present in basophil granules.
• Function of Histamine: It is a vasodilator, meaning it widens blood vessels. This draws additional immune cells to the damaged or infected area.
• Function of Heparin: It has anti-coagulant properties (blood thinner). The body produces it to prevent blood clots from forming at the site of an injury or infection.
• Additionally, basophils indirectly target foreign agents by binding to B-cell lymphocytes.
• As a result of the binding, B-cells release antibodies known as immunoglobulin E (IgE) into the bloodstream.
• IgE possesses potent anti-parasite and anti-venom properties.

Basophils Role in Allergies

• An allergy occurs when the immune system reacts abnormally to an otherwise harmless chemical or event.
• The release of histamine by basophils is one of the primary causes of allergy symptoms.
• When the body is exposed to allergens, basophils and similar cells called mast cells burst open (allergy-causing chemical).
• Histamine causes blood arteries to widen, allowing surrounding tissues to receive fluid.
• As these tissues expand and become inflamed, they can cause skin inflammation, redness, and itching in the form of rashes and hives.

Levels of Basophils – Normal Range of Basophils

• The concentration of white blood cells, of which basophils comprise between 0.5 and 1 percent, is determined by a test called a white blood cell (WBC) count.
• Absolute basophil count (ABC) is a test that measures the precise amount of basophils in millilitres (mm3).
• The usual range for basophils is 0.5% to 1% of the total white blood cell count. This corresponds to zero to 300 basophils per microliter of blood in healthy humans.
• If your basophil count exceeds this threshold, you may be suffering from allergic responses, chickenpox, collagen vascular disease, hyperthyroidism, or bone marrow illness.
• Cancer, acute infection, and thyrotoxicosis are denoted by a decrease in basophils.
• Blood testing may reveal elevated or depleted levels of basophils in response to particular illnesses or treatments.
• Basophilia is characterised by an abnormally high basophil count, and basopenia is characterised by an abnormally low basophil count.

Diseases related to high basophil counts

• Allergic reactions: Basophils are involved in the immune response to allergens, so a high basophil count may be seen in people with allergies or allergic reactions.
• Parasitic infections: Basophils play a role in fighting parasitic infections, so a high basophil count may be seen in people with these types of infections.
• Chronic myelogenous leukemia: This is a type of cancer that can cause an increase in the number of basophils in the blood.

Diseases related to low basophil counts

There is not a specific disease that is caused by a low count of basophils, but a low count can be a sign of an underlying health condition. In some cases, a low count of basophils may be related to a problem with the bone marrow or immune system.

For example, a low count of basophils can occur in myelodysplastic syndromes, a group of disorders that affect the production of blood cells in the bone marrow. It can also occur in some types of leukemia, such as acute lymphocytic leukemia or chronic myelogenous leukemia.

In addition, a low count of basophils may be a side effect of certain medications, such as corticosteroids, which are often used to treat inflammatory conditions such as asthma and rheumatoid arthritis.

If you have a low count of basophils, your healthcare provider will likely want to do additional testing to determine the underlying cause. Treatment will depend on the underlying condition and may include medications, such as growth factors or immune-modulating drugs, or more intensive therapies, such as chemotherapy or bone marrow transplantation.

Causes of Low count of basophil

There are several possible causes of a low count of basophils, also known as basopenia. Some of the most common causes include:

1. Corticosteroid use: Corticosteroids are medications that are commonly used to treat a variety of inflammatory conditions, such as asthma and rheumatoid arthritis. However, they can also lower the number of basophils in the blood.
2. Radiation therapy: Radiation therapy, which is used to treat cancer, can damage the bone marrow and lead to a decrease in the number of basophils.
3. Myelodysplastic syndromes: Myelodysplastic syndromes are a group of disorders that affect the bone marrow’s ability to produce enough healthy blood cells, including basophils.
4. Blood cancers: Certain types of blood cancers, such as acute lymphocytic leukemia and chronic myelogenous leukemia, can cause a decrease in the number of basophils.
5. Autoimmune disorders: Some autoimmune disorders, such as lupus and rheumatoid arthritis, can cause a decrease in the number of basophils.
6. Infections: In some cases, certain types of infections can cause a decrease in the number of basophils, although this is less common.

Causes of Low count of basophil

A high count of basophils, also known as basophilia, can be caused by several different factors. Here are some of the most common causes:

1. Allergic reactions: Basophils are involved in the immune response to allergens, so a high basophil count may be seen in people with allergies or allergic reactions.
2. Parasitic infections: Basophils play a role in fighting parasitic infections, so a high basophil count may be seen in people with these types of infections.
3. Chronic myelogenous leukemia: This is a type of cancer that can cause an increase in the number of basophils in the blood.
4. Inflammatory disorders: Some inflammatory disorders, such as ulcerative colitis and rheumatoid arthritis, can cause a high basophil count.
5. Stress: Stress can trigger the release of certain hormones that can cause a temporary increase in the number of basophils.
6. Thyroid disorders: Some thyroid disorders, such as hypothyroidism, can cause a high basophil count.
7. Certain medications: Certain medications, such as heparin and certain types of antibiotics, can cause a high basophil count.

Method of basophil count

Basophil count is typically measured through a complete blood count (CBC) test, which is a routine blood test that measures various components of the blood, including the number of basophils.

To perform a basophil count, a healthcare provider will take a small sample of blood, usually from a vein in the arm. The blood sample is then sent to a laboratory for analysis.

In the laboratory, the blood sample is analyzed using an automated machine that counts the number of different types of blood cells, including basophils. The results of the CBC test are reported as a number of cells per microliter of blood.

The normal range for basophil count is usually between 0 and 2% of the total white blood cell count. However, the specific normal range may vary slightly depending on the laboratory and the person’s age, gender, and overall health.

If the basophil count is outside of the normal range, further testing may be needed to determine the underlying cause. This may include additional blood tests or other diagnostic tests, such as bone marrow biopsy.

Function of Basophils

Basophils play several important functions in the immune system. Here are some key functions of basophils:

1. Immune Response against Parasitic Infections: Basophils are crucial for initiating and coordinating the immune response against parasitic infections, particularly those caused by helminths (parasitic worms). They release various mediators and cytokines that help in combating the parasites and activating other immune cells to eliminate the infection.
2. Antigen-Presenting Cell Activity: Basophils have been shown to possess antigen-presenting cell (APC) capabilities. They can capture antigens and present them to T cells, facilitating the differentiation of antigen-specific CD4 T cells into Th2 cells. This process is essential for mounting an effective immune response, especially in allergic reactions.
3. Cross-Talk with Other Immune Cells: Basophils engage in cross-talk with other immune cells, such as mast cells, dendritic cells, and T cells. This communication helps to maintain an orchestrated mechanism of allergy and immune responses. Basophils can modulate the functions of other immune cells through the release of various mediators and cytokines.
4. Modulation of Hypersensitive Response: Basophils contribute to the regulation of hypersensitive responses. They can modulate the releasibility of histamine and lipid mediators, which are involved in allergic reactions. Basophils help to fine-tune the immune response, preventing excessive allergic reactions while still providing an effective defense against allergens.
5. Basophil Activation Test: The basophil activation test is a diagnostic test that has been developed to assess allergic reactions to different substances such as foods, venoms, and drugs. This test measures the activation and degranulation of basophils in response to specific allergens, aiding in the diagnosis of allergies.
6. B Cell Maturation and IgE Production: Basophils play a role in B cell maturation, particularly in the production of immunoglobulin E (IgE). IgE antibodies are involved in allergic responses. Basophils can stimulate B cells to produce IgE, which contributes to the allergic immune response.

Overall, basophils are key players in the immune system, involved in combating parasitic infections, modulating allergic reactions, facilitating immune cell communication, and contributing to the production of IgE antibodies. Their functions are diverse and critical for maintaining immune homeostasis and mounting appropriate immune responses.

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References

• Sticco KL, Pandya NK, Lynch DT. Basophilia. [Updated 2022 Oct 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535365/
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