Basophils- Definition, Structure, Immunity and Functions

Basophils are a type of white blood cell that belong to the granulocyte family. Granulocytes are named after the granules they contain in their cytoplasm, which are filled with various substances that help them fight infections and inflammation. Basophils have large and dark granules that stain with basic dyes, hence the name "basophil".

Basophils are the least common type of granulocyte, accounting for only about 0.5% of the total white blood cells in the blood. They are produced in the bone marrow from stem cells and circulate in the bloodstream for a few hours before migrating to the tissues. Basophils have a short lifespan of about 60 hours and are constantly replaced by new cells.

Basophils play an important role in the immune system, especially against parasitic infections and allergic reactions. They can sense foreign substances, such as antigens, allergens, or pathogens, and release various mediators that trigger inflammation and attract other immune cells. Some of these mediators include histamine, leukotrienes, cytokines, and chemokines.

Basophils are also involved in the regulation of the adaptive immune response, which is the specific and long-lasting immunity against a particular antigen. Basophils can act as antigen-presenting cells that activate T cells and B cells, and they can also produce cytokines that influence the differentiation of T helper cells into different subsets. Basophils are particularly associated with the Th2 subset, which promotes antibody production and allergic responses.

Basophils have many similarities with mast cells, another type of granulocyte that resides in the tissues. Both basophils and mast cells have high-affinity receptors for immunoglobulin E (IgE), which is an antibody that binds to allergens and triggers degranulation. Both basophils and mast cells also release similar mediators that cause allergic symptoms, such as itching, swelling, sneezing, and wheezing.

However, basophils and mast cells also have some differences in their origin, location, morphology, and function. Basophils are derived from hematopoietic stem cells in the bone marrow and circulate in the blood, while mast cells are derived from multipotent progenitors in the peripheral tissues and remain there. Basophils have a lobed nucleus and round granules, while mast cells have a round nucleus and oval granules. Basophils can present antigens to T cells and B cells, while mast cells cannot. Basophils can also respond to other stimuli besides IgE, such as cytokines, complement components, or parasite-derived molecules.

In this article, we will explore the definition, structure, immunity, and functions of basophils in more detail. We will also compare basophils with eosinophils and mast cells, two other types of granulocytes that are involved in allergic and parasitic responses. We will also discuss the role of IgE in basophil function and the role of chitin in basophil development. Finally, we will review some of the clinical implications of basophil activation and dysfunction in various diseases.

Basophils are a type of white blood cell that are produced in the bone marrow and circulate in the blood. They are part of the immune system and play a role in defending the body against pathogens, especially parasites, and in mediating allergic reactions .

Basophils are the smallest in number of all white blood cells, accounting for less than 1% of the total leukocytes . They are also the largest in size among the granulocytes, which are white blood cells that contain granules in their cytoplasm . The other granulocytes are neutrophils and eosinophils.

Basophils can be identified by their dark purple-black granules that fill most of their cytoplasm and obscure their two-lobed nucleus . The granules contain various substances that are released when basophils are activated by an immune stimulus, such as histamine, heparin, leukotrienes, cytokines, and chemokines .

Basophils are activated by the binding of immunoglobulin E (IgE) antibodies to their surface receptors, called FcεRI . IgE antibodies are produced by plasma cells in response to specific antigens, such as allergens or parasitic proteins. When basophils encounter these antigens, they cross-link the IgE antibodies on their surface and trigger a cascade of signals that lead to degranulation and secretion of inflammatory mediators .

The mediators released by basophils have various effects on the immune system and the tissues. Histamine causes vasodilation, increased vascular permeability, smooth muscle contraction, and itching . Heparin prevents blood clotting and facilitates the migration of other immune cells to the site of inflammation . Leukotrienes enhance vascular permeability, bronchoconstriction, and mucus secretion . Cytokines and chemokines modulate the activation and differentiation of other immune cells, especially T helper 2 (Th2) cells that promote humoral immunity and allergic responses .

Basophils play an important role in immunity against parasitic infections, especially helminths (worms). They produce large amounts of interleukin-4 (IL-4), which stimulates Th2 cells to produce more IgE antibodies and eosinophils to kill the parasites . Basophils can also act as antigen-presenting cells that present parasitic antigens to Th2 cells and enhance their activation .

Basophils are also involved in allergic reactions, such as hay fever, asthma, urticaria, and anaphylaxis. They release histamine and other mediators that cause the symptoms of allergy, such as sneezing, itching, wheezing, swelling, and shock . Basophil activation tests (BATs) can be used to diagnose specific allergies by measuring the level of basophil degranulation after exposure to different allergens.

Basophils have a short lifespan of a few hours to a few days. They are removed from the circulation by macrophages in the spleen or liver or by apoptosis (programmed cell death) .

Basophils, eosinophils and mast cells are three types of granulocytes that are involved in allergic and inflammatory reactions. They share some common features, such as the expression of high-affinity receptors for IgE (FcεRI) and the release of granule-derived mediators like histamine and leukotrienes. However, they also have distinct characteristics that reflect their different roles and functions in the immune system.

Basophils

Basophils are the least common and smallest granulocytes, accounting for less than 1% of circulating leukocytes. They are derived from granulocyte-monocyte progenitors in the bone marrow and circulate in the blood as mature cells. Basophils are activated by IgE cross-linking, parasite-derived molecules, or cytokines like IL-3 and IL-33. Upon activation, basophils release preformed mediators such as histamine, heparin, proteases, and lipid mediators, as well as newly synthesized cytokines such as IL-4, IL-13, TNF-α, and IL-6. Basophils play a crucial role in initiating and amplifying Th2 immune responses against parasites and allergens by producing IL-4 and presenting antigens to T cells. Basophils can also modulate inflammation by releasing anti-inflammatory mediators like IL-10 or by inhibiting mast cell degranulation.

Eosinophils

Eosinophils are granulocytes that have a characteristic bilobed nucleus and cytoplasmic granules that stain red with eosin. They constitute about 1-6% of circulating leukocytes and are mainly found in tissues such as the skin, lungs, gastrointestinal tract, and lymph nodes. Eosinophils are derived from granulocyte-monocyte progenitors in the bone marrow and differentiate under the influence of cytokines like IL-3, IL-5, and GM-CSF. Eosinophils are activated by IgE cross-linking, complement components, chemokines, or cytokines like IL-4 and IL-13. Upon activation, eosinophils release preformed mediators such as major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and lipid mediators, as well as newly synthesized cytokines such as IL-4, IL-5, IL-13, TNF-α, and IFN-γ. Eosinophils play a key role in combating parasitic infections by releasing cytotoxic granule proteins and reactive oxygen species. Eosinophils also contribute to allergic inflammation by inducing tissue damage, mucus secretion, smooth muscle contraction, and nerve stimulation.

Mast cells

Mast cells are granulocytes that have a round or oval nucleus and cytoplasmic granules that stain blue with toluidine blue. They are widely distributed in various tissues such as the skin, mucosa, connective tissue, and vascular system. Mast cells are derived from hematopoietic stem cells in the bone marrow and migrate to tissues where they mature under the influence of growth factors like stem cell factor (SCF) and nerve growth factor (NGF). Mast cells are activated by IgE cross-linking, complement components, neuropeptides, or cytokines like IL-1 and IL-33. Upon activation, mast cells release preformed mediators such as histamine, heparin, proteases, tryptase, chymase, carboxypeptidase A3 (CPA3), and lipid mediators, as well as newly synthesized cytokines such as TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, and IL-17. Mast cells play a central role in mediating immediate hypersensitivity reactions by causing vasodilation, increased vascular permeability, smooth muscle contraction, mucus secretion, pruritus

IgE is a type of antibody that is involved in allergic reactions and immunity against parasites. IgE binds to specific antigens on the surface of pathogens or allergens and triggers a cascade of events that leads to the activation of basophils and other immune cells.

Basophils are granulocytes that express high-affinity receptors for IgE, called FcεRI, on their surface. These receptors can bind to IgE molecules that are already attached to antigens, forming a cross-link between the two. This cross-linkage activates the basophils and causes them to release various inflammatory mediators, such as histamine, leukotrienes, cytokines, and chemokines .

The release of these mediators has several effects on the immune response and the allergic reaction. For example, histamine increases the permeability of blood vessels and causes smooth muscle contraction, leading to symptoms such as itching, swelling, and bronchoconstriction. Leukotrienes also contribute to bronchoconstriction and mucus secretion, as well as attracting other immune cells to the site of inflammation. Cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and tumor necrosis factor-alpha (TNF-α), modulate the differentiation and activation of T cells, B cells, mast cells, eosinophils, and macrophages .

One of the main functions of basophils is to promote the Th2 type of immune response, which is characterized by the production of IgE antibodies and the activation of eosinophils and mast cells. Basophils can act as antigen-presenting cells and stimulate naïve T cells to differentiate into Th2 cells by secreting IL-4 and IL-13. These cytokines also induce B cells to switch their antibody class to IgE and enhance the production of IgE by plasma cells. Furthermore, basophils can enhance the survival and function of mast cells by providing them with IL-3 .

The Th2 type of immune response is beneficial for fighting against parasitic infections, especially helminths, which are large multicellular worms that can evade phagocytosis by macrophages. IgE antibodies can bind to antigens on the surface of helminths and activate basophils, eosinophils, and mast cells to release cytotoxic granules that damage the parasite`s membrane. Eosinophils can also secrete major basic protein (MBP) and eosinophil cationic protein (ECP), which have anti-parasitic properties .

However, the Th2 type of immune response can also cause harmful effects when it is directed against harmless antigens, such as pollen, dust mites, or food proteins. This results in allergic reactions or hypersensitivity disorders, such as allergic rhinitis, asthma, atopic dermatitis, food allergy, or anaphylaxis. In these conditions, IgE antibodies bind to allergens and activate basophils and other effector cells to release inflammatory mediators that cause tissue damage and symptoms .

Therefore, IgE plays a crucial role in basophil function by acting as a bridge between antigens and FcεRI receptors on basophils. This leads to the activation of basophils and the release of various mediators that modulate the immune response and the allergic reaction. The balance between protective and pathological effects of IgE depends on the nature and dose of the antigen, as well as the genetic and environmental factors that influence IgE production and regulation .

Basophils are the smallest granulocytes with a diameter ranging between 10-14 µm. These polymorphonuclear cells have a polylobed nucleus and prominent, brightly metachromatic cytoplasmic granules.

The nucleus contains condensed nuclear chromatin, but the nucleolus is absent. The cytoplasm contains organelles like mitochondria, vesicles, glycogen, and granules. The mature granules usually contain dense particles.

Usually, human basophil cytoplasmic granules are round to angular, membrane-bound structures with sizes ranging up to 1.2 µm. The substructure of these granules contains dense particles in a less dense matrix occasional complex membrane.

The cytoplasm has a complex vesicular system that is involved in basophil degranulation in the presence of an appropriate stimulus.

The structure of basophils is similar to mast cells, and the differentiation can be made on the basis of glycogen content and the plasmalemma ridges. Basophils have a higher glycogen content in the cytoplasm, whereas these lack the plasmalemmal ridges and folds that are present in mast cells.

Basophils also express various surface markers that can be used to identify and distinguish them from other leukocytes. Some of the common markers include ckit–FcεRI+, CD11b+, IL-3Rhi, etc. Basophils also express high-affinity receptors for IgE (FcεRI) and IgG (FcγRIIb), which mediate their activation by antigen-bound antibodies.

The structure of basophils is adapted to their functions as innate immune cells that release inflammatory mediators and cytokines in response to parasitic infections and allergic reactions.

Basophils are a type of white blood cell that play a role in identifying and destroying bacteria and foreign proteins. Basophils defend against bacteria, viruses and fungi by surrounding and ingesting them (phagocytosis). Basophils are also involved in allergic reactions and parasitic infections, as they release histamine and heparin, which increase blood flow and inflammation. Basophils also produce immunoglobulin E (IgE), which binds to allergens and triggers the release of more histamine and other mediators.

Basophils are formed from the granulocyte-monocyte progenitor cells of the bone marrow, which are then released into the peripheral blood as fully differentiated cells. The differentiation of precursor cells into the basophil lineage is dependent on the transcription factor, C/EBPα. The level of basophils in the blood remains maintained under normal conditions, but the number increases as a result of parasitic infections or allergies.

The exact nature of stimuli responsible for basophil development during parasitic infections is not clear yet, but the hematopoietic cytokine IL-3 has been suggested to play an essential role. Other parasite-associated molecules like proteases, glycoproteins, or structural components like chitin can also act as stimuli for the differentiation of basophils.

Basophils, like mast cells, are activated by the cross-linkage between the surface IgE receptor, FcεRI, and the IgE antibodies present in the blood. The binding of IgE to basophils results in an activation signal which causes a rapid release of intracellular mediators like histamine and leukotrienes. The increased level of these compounds causes increased secretion of cytokines like IL-4 by basophils.

Besides, IL-4-independent pathways involving IL-3 have also been described, which result in basophil activation. Activated basophils produce a large amount of IL-4, which might even be greater than that produced by T cells. The IL-4 produced by basophils induces the activation of parasite-specific naïve T cells to Th2 type effector T cells.

The following are some of the roles of basophils in immunity:

• Basophils are important for the induction of immune response against parasitic infections, especially infections involving helminths. Basophils release histamine and other mediators that increase vascular permeability and recruit eosinophils and other inflammatory cells to the site of infection. Basophils also secrete cytokines that promote Th2 differentiation and IgE production, which enhance parasite clearance.
• Basophils can function as professional antigen-presenting cells required for T cell differentiation. Basophils, once bound to IgE, lead to the differentiation of antigen-specific CD4 T cells into Th2 cells. Basophils can also present antigens to CD8 T cells and induce cytotoxic responses.
• Basophils work with other immune cells via cross-talk to maintain an orchestrated mechanism of allergy. Basophils interact with mast cells, dendritic cells, B cells, T cells and regulatory T cells to modulate the allergic response. Basophils can also decrease hypersensitive response by the modulation of releasibility of either histamine or lipid mediators.
• Basophils activation test is a test developed to test allergic reactions to different foods, venoms, and drugs. The test measures the expression of activation markers on basophils after exposure to specific allergens. The test can help diagnose allergic diseases and monitor immunotherapy.
• One of the important physiological roles of basophils is the B cell maturation, resulting in IgE production. Basophils secrete IL-4 and IL-13 that stimulate B cell proliferation and class switching to IgE. Basophils can also provide survival signals to B cells via CD40L expression.

Chitin is a polysaccharide that forms the structural component of the exoskeletons of arthropods and the cell walls of fungi. Chitin is also present in some parasites, such as helminths and protozoa, and can trigger immune responses in the host.

One of the immune cells that can recognize and respond to chitin is the basophil. Basophils express chitin receptors on their surface, such as Dectin-1 and CD23, which can bind to chitin fragments and activate basophils.

Activation of basophils by chitin leads to the release of cytokines, such as IL-4 and IL-13, which promote Th2 differentiation and IgE production. These cytokines also enhance the expression of chitin receptors on basophils, creating a positive feedback loop that amplifies the basophil response to chitin.

Chitin also plays a role in the development of basophils from their progenitors in the bone marrow. Chitin induces the expression of C/EBPα, a transcription factor that is essential for basophil differentiation. Chitin also stimulates the proliferation and survival of basophil progenitors by activating the PI3K/Akt pathway.

The role of chitin in basophil development is more evident during parasitic infections, especially those involving helminths. Helminths secrete or shed chitin-containing molecules that can stimulate basophil production and activation in the host. Basophils then contribute to the anti-helminth immune response by producing IL-4 and IL-13, which induce eosinophilia, mucus production, and smooth muscle contraction.

The role of chitin in basophil development is also relevant for allergic diseases, such as asthma and atopic dermatitis. Exposure to environmental allergens, such as house dust mites and fungi, can result in the inhalation or ingestion of chitin fragments that can activate basophils. Basophils then release histamine and leukotrienes, which cause bronchoconstriction and inflammation. Basophils also produce IL-4 and IL-13, which promote IgE synthesis and Th2 polarization.

Therefore, chitin is an important factor that regulates basophil development and function in both parasitic infections and allergic diseases. Chitin can act as a danger signal that alerts the immune system to the presence of potential pathogens or allergens. Chitin can also modulate the balance between Th1 and Th2 responses by influencing basophil cytokine production.

Basophils are involved in both innate and adaptive immune responses against parasitic infections and allergens. Some of the functions of basophils in these contexts are:

• Basophils secrete various mediators that modulate the vascular permeability and smooth muscle contraction, facilitating the recruitment and migration of other immune cells to the site of infection or inflammation. Some of these mediators include histamine, leukotrienes, prostaglandins, platelet-activating factor, and nitric oxide.
• Basophils produce cytokines and chemokines that regulate the differentiation and activation of other immune cells, especially Th2 cells and B cells. Some of these cytokines and chemokines include IL-4, IL-13, IL-25, IL-33, TSLP, CCL2, CCL7, and CCL11.
• Basophils act as antigen-presenting cells that capture and process antigens from parasites or allergens and present them to naïve CD4 T cells via MHC class II molecules. This leads to the polarization of T cells into Th2 cells that produce IL-4, IL-5, IL-9, and IL-13. These cytokines promote the production of IgE antibodies by B cells, the activation and recruitment of eosinophils and mast cells, and the induction of mucus secretion and airway hyperresponsiveness.
• Basophils express high-affinity receptors for IgE (FcεRI) that bind to IgE antibodies specific for parasitic or allergenic antigens. Upon cross-linking of FcεRI by antigen-bound IgE, basophils undergo degranulation and release preformed mediators like histamine, heparin, proteases, and cytokines. These mediators contribute to the immediate hypersensitivity reactions like anaphylaxis, urticaria, angioedema, and asthma.
• Basophils also express low-affinity receptors for IgG (FcγRIIb) that bind to IgG antibodies specific for parasitic or allergenic antigens. Upon cross-linking of FcγRIIb by antigen-bound IgG, basophils undergo negative regulation and inhibit their degranulation and cytokine production. This mechanism provides a feedback loop to limit the excessive basophil activation and inflammation.
• Basophils can also interact with other cell types like dendritic cells, natural killer cells, regulatory T cells, innate lymphoid cells, and epithelial cells via various surface molecules and soluble factors. These interactions modulate the immune response by enhancing or suppressing the basophil functions depending on the context.

In summary, basophils play a crucial role in the immune response against parasites and allergens by producing various mediators that affect the vascular tone, the inflammatory milieu, the adaptive immunity, and the tissue homeostasis. Basophils can also regulate their own functions by responding to different signals from antibodies or other cell types. Basophils are therefore important targets for therapeutic interventions in parasitic infections and allergic diseases.

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