What are Eosinophils?

• Eosinophils are a type of white blood cells that play a crucial role in the body’s defense against parasitic infections and other immune responses. These cells are motile and phagocytic, meaning they can move and engulf foreign substances, including parasites. Eosinophils are derived from the bone marrow and have a relatively short lifespan in the bloodstream, preferring to reside in various tissues.
• The functions of eosinophils are diverse and multifaceted. They are involved in antigen presentation, which is the process of displaying foreign substances to other immune cells for recognition and response. Eosinophils also release peptides, lipids, and cytokine mediators, which are important in immune signaling and regulation. However, in certain conditions like malignant neoplasms, autoimmune disorders, and connective tissue disorders, eosinophils can also be implicated.
• Normally, eosinophils constitute about 6% of the total circulating leukocytes in the bloodstream. They can be found in various tissues such as the lungs, thymus, mammary glands, spleen, and uterus. Traditionally, it was believed that eosinophils leaving the bone marrow were mature cells. However, recent research has revealed the existence of multiple tissue-specific subtypes of eosinophils, distinguished by their expression of specific cell surface markers.
• The recruitment of eosinophils from the bloodstream to specific locations and inflammatory sites is mediated by eosinophil-specific chemokines and other stimuli. Once at the site of infection or inflammation, eosinophils remain localized, particularly around invading parasites. They release proteins that can damage the membranes of these parasites, aiding in their elimination. Additionally, eosinophils have been implicated in asthma and allergy symptoms, particularly in areas where parasitic infections are less prevalent.
• Certain medical conditions are associated with eosinophils, such as eosinophilia, where the number of eosinophils in the bloodstream is elevated (ranging between 450-550 cells/µL). Eosinophilia can be indicative of underlying diseases or infections that need further investigation and treatment.
• Eosinophils, also known as eosinophiles or acidophils, are a type of white blood cell involved in combating multicellular parasites and certain infections. Alongside mast cells and basophils, eosinophils are crucial in controlling mechanisms associated with allergies and asthma. These granulocytes develop in the bone marrow and migrate into the bloodstream, where they do not multiply. Eosinophils are characterized by their eosinophilic or acid-loving nature, evident by their large acidophilic cytoplasmic granules. These granules contain various chemical mediators that are released upon activation, contributing to the elimination of parasites and tissue damage.
• In a healthy individual, eosinophils make up about 1-3% of white blood cells. They are approximately 12-17 micrometers in size and possess bilobed nuclei. While eosinophils are released into the bloodstream, they primarily reside in tissues. They can be found in specific locations such as the thymus, lower gastrointestinal tract, ovaries, uterus, spleen, and lymph nodes. However, under normal conditions, eosinophils are not present in organs like the lungs, skin, esophagus, or some other internal organs. Their presence in these organs is often associated with diseases or inflammatory conditions.
• The lifespan of eosinophils in circulation is relatively short, around 8-12 hours, but they can survive for an additional 8-12 days in tissues without stimulation. This longevity is unique among granulocytes and was discovered through pioneering work in the 1980s, demonstrating the remarkable survival capabilities of eosinophils after maturation.
• Overall, eosinophils play a crucial role in immune responses, particularly in defense against parasites and modulation of allergic and asthmatic reactions. Their distinct characteristics and functions make them an essential component of the body’s immune system.

Definition of Eosinophils

Eosinophils are a type of white blood cells that are involved in combating parasites, regulating allergic reactions, and supporting immune responses. They have distinctive granules in their cytoplasm and play a crucial role in maintaining immune system balance.

Characteristics of Eosinophil

Eosinophils possess several distinctive characteristics:

1. Granulocytic Phagocytes: Eosinophils are a type of granulocytic phagocytes, meaning they can engulf and destroy foreign substances such as pathogens.
2. Acidic Cytoplasm and Eosine Staining: Eosinophils have acidic cytoplasm, and they are specifically stained with eosine dye, which gives them a distinctive reddish appearance.
3. Diameter: Eosinophils typically measure around 8 micrometers in diameter.
4. Percentage in Total Leukocytes: Eosinophils make up about 1% to 5% of the total leukocyte population in the bloodstream.
5. Role in Immune Response: Eosinophils play a critical role in the host’s immune response against certain types of endoparasitic infections, such as schistosomiasis and helminthic infections.
6. Derived from Hematopoietic Stem Cells (HSC): Eosinophils are derived from myeloid progenitor-lineage Hematopoietic Stem Cells (HSC) in the bone marrow.
7. Membrane-Bound Receptors: Eosinophils possess membrane-bound receptors for immunoglobulin G (IgG) and immunoglobulin E (IgE), which are involved in immune signaling and response.
8. Regulation of Differentiation and Development: The differentiation and development of eosinophils from myeloid progenitors in the bone marrow are regulated by various factors such as Stem Cell Factor (SCF), Interleukin-3 (IL-3), Interleukin-4 (IL-4), Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and Eotaxin (CCL11).
9. Coordination of Maturation and Release: Interleukin-5 (IL-5) and Eotaxin (CCL11) play a role in coordinating the ultimate differentiation, maturation, and release of eosinophils into the bloodstream.
10. Granular Contents Release: During immunological reactions, eosinophils release the contents of their granules, which contain various toxic proteins and enzymes. These granular contents contribute to the immune response and can be harmful to both parasites and host tissues.

These characteristics collectively define the unique properties and functions of eosinophils in the immune system.

Structure of Eosinophils

The structure of eosinophils is characterized by several key features:

1. Size and Nucleus: Eosinophils are granulocytes and typically measure between 10-16 µm in diameter. They have a segmented or bi-lobed nucleus, where the ratio of nuclei to cytoplasm is approximately 30%.
2. Cytoplasmic Granules: A notable morphological feature of eosinophils is the presence of cytoplasmic granules. These granules contain specific cationic proteins, which are responsible for the distinct characteristics of eosinophils.
3. Unique Granule Structure: The specific granules of eosinophils have a unique structure. They consist of a crystalloid core, a dense matrix surrounded by a membrane. This core is crucial for the essential properties of eosinophils.
4. Mediator Content: The granules of eosinophils also contain various mediators, including proteins, cytokines, chemokines, and enzymes. These mediators can induce inflammation and tissue damage, contributing to immune responses.
5. Cytoplasmic Components: The cytoplasm of eosinophils contains other cellular components such as Golgi bodies, endoplasmic reticulum, and mitochondria. These structures play roles in protein synthesis and ATP production within the cell.
6. Histological Structure and Activation: The histological structure of eosinophils can vary depending on the level of cell activation. During piecemeal degranulation, vesicles can be observed in the cell as part of the activation process.
7. Plasma Membrane and Receptors: The plasma membrane of eosinophils contains numerous receptors that are specific to certain cytokines. These receptors regulate the maturation and other physiological functions of the cell, allowing for the appropriate response to immune signals.

Overall, the structure of eosinophils, including their size, nucleus, granules, and cellular components, enables them to carry out their functions in the immune system and participate in immune responses and inflammation.

Granular Content of Eosinophil 

The granule in the cytoplasm of the eosinophil is the primary enzyme responsible for the eosinophil’s function. The following are contained in the granule:

• Mazor Basic Protein – Also known as MBP, is a protein that stimulates the degranulation of mast cells and basophils. These proteins are also involved in the remodelling of peripheral nerves.
• Eosinophil Cationic Protein – These proteins (ECP) are accountable for producing pores in the pathogen’s membrane. The creation of pores is crucial because it allows the cytotoxic molecule of the host to enter the pathogen’s body and induce cell death via membrane disintegration. It stimulates fibroblast glycosaminoglycan secretion. Additionally, it inhibits antibody production and T-cell proliferation.
• Eosinophil Peroxidase- It encourages the development of reactive oxygen species and reactive nitrogen species intermediates. The synthesis of these substances in the pathogen’s body induces oxidative stress, leading to apoptosis and necrosis-mediated cell death.
• Eosinophil-Derived Neurotoxin – The Eosinophil-Derived Neurotoxin is an antiviral RNAse. They typically inhibit the pathogen’s transcription machinery.

How Eosinophils work against pathogens? (Immunity)

Eosinophils play a vital role in the immune response against pathogens through various mechanisms:

1. Formation and Maturation: Eosinophils are formed from hematopoietic stem cells in the bone marrow under the influence of soluble mediators and transcription factors. They undergo maturation and acquire specific molecular systems.
2. Docking and Fusion: Mature eosinophils possess a molecular system that allows the docking and fusion of vesicles with the cell membrane. This process facilitates the release of proteins and other components stored inside the vesicles through regulated exocytosis.
3. Degranulation: Eosinophils undergo degranulation, where they release proteins, enzymes, and other mediators stored in their vesicles. This process contributes to the elimination of pathogens and modulating immune responses.
4. Antigen Presentation: Eosinophils have been associated with antigen presentation to T cells. After allergen exposure, eosinophils express machinery for antigen presentation, including major histocompatibility complex class II (MHC II) molecules and co-stimulatory molecules. This allows them to present antigens to T cells and initiate specific immune responses.
5. Migration and Proliferation: Eosinophils present in tissues can migrate to draining lymph nodes, reaching the proliferation zone. The migration process is independent of the eotaxin receptor CCR3. Once in the lymph nodes, antigen-presenting eosinophils promote antigen-specific T-cell proliferation, contributing to the amplification of the immune response.
6. Adherence and Transmigration: Eosinophils accumulate at sites of inflammation through a series of interactions that allow them to adhere to and transmigrate through the endothelium layer. Multiple pathways are involved in this process, including CD18-dependent pathways, adherence to E-selectin and P-selectin.
7. Recruitment and Movement: In cases of allergen-induced eosinophil recruitment, the movement of cells is dependent on CD4+ T cells and interferon-gamma (IFN-γ). These factors guide the eosinophils to the specific site of inflammation.

Through these mechanisms, eosinophils contribute to the immune response against pathogens by directly combating them, presenting antigens to initiate immune reactions, and collaborating with other immune cells to enhance the overall immune response.

Functions of Eosinophil

Eosinophils serve various functions in the body, including:

1. Defense against Parasitic Infections: Eosinophils play a crucial role in the host’s defense against parasitic infections. They are particularly effective in combating multicellular parasites such as helminths. Eosinophils release toxic proteins and enzymes that can kill or immobilize parasites.
2. Mediators of Inflammation and Host Defense: Eosinophils release lipid, peptide, and cytokine mediators that contribute to inflammation and host defense. These mediators can attract and activate other immune cells, enhance the immune response, and promote tissue repair.
3. Antigen Presentation: Eosinophils can function as antigen-presenting cells. They have the ability to express major histocompatibility complex class II (MHC II) proteins, which are necessary for presenting antigens to T cells. This antigen presentation can initiate immune responses and help coordinate the immune system’s defense against pathogens.
4. Release of Lipid Mediators: Eosinophils are effector cells that release lipid mediators such as leukotriene C4, lipoxins, and platelet-activating factor (PAF). These lipid mediators contribute to the acute manifestations of allergic or immunological responses, including bronchoconstriction, vasodilation, and increased vascular permeability.
5. Regulation of Mast Cell Functions: Eosinophils have the potential to regulate mast cell functions. They can release granule proteins and cytokines that influence mast cell activity. This interaction between eosinophils and mast cells is important in the modulation of allergic and inflammatory responses.
6. Cytokine Release and T Cell Activation: Eosinophils secrete various cytokines, including interleukin-2 (IL-2), IL-4, IL-6, and IL-12. These cytokines can promote T cell proliferation and activation, as well as the polarization of T helper cell subsets (Th1 or Th2), which are involved in different aspects of immune responses.
7. Contribution to Airway Hyperreactivity and Asthma: Eosinophils in the lungs have been identified as significant contributors to airway hyperreactivity and asthma. Their presence and activation in the airways can lead to inflammation, bronchoconstriction, and the development of asthma symptoms.

Overall, eosinophils have diverse functions in immune responses, including defense against parasites, modulation of inflammation, antigen presentation, regulation of other immune cells, and involvement in allergic and respiratory conditions.

What is Eosinophilia?

• It is a disorder characterised by an elevated absolute eosinophil count in the blood.
• Absolute eosinophil count is a blood test that measures the cell concentration.
• When a person has more than 500 eosinophils per microliter, eosinophilia is identified.
• Increased eosinophil count may be an indication of Acute hypereosinophilic syndrome, eczema (skin disorder, itchy or irritated skin), asthma, or hay fever, as well as many autoimmune disorders.
• In addition to being a sign of leukaemia, eosinophilia is also used to diagnose the early stages of Cushing’s illness, which is characterised by an abnormally elevated cortisol concentration.
• The reduced number of eosinophils or their low concentration can be related to alcohol consumption. A individual suffering from Cushing’s syndrome also has abnormally low eosinophil levels.
• In general, low levels of eosinophils are not life-threatening unless all other white blood cell counts are also abnormally low. Typically, these disorders result from an anomaly or dysfunction in the bone marrow.
• Eosinophilic disorders in the body include eosinophilic esophagitis, a disorder of the gastrointestinal tract, specifically the oesophagus; this is commonly known as esophageal eosinophilia.
• Eosinophilic colitis, which is eosinophilia of the large intestine, is another disorder. Eosinophilia can affect a variety of organs, however these are the most commonly affected.

Types of Eosinophilia

Eosinophilia can be primary or secondary:

Primary causes

• Leukemia eosinophilic chronique.
• Myeloid and lymphoid tumours having PDGFRA, PDGFRAB, or FGFR1 gene rearrangements.
• Eosinophilia hereditary
• Syndrome of idiopathic hypereosinophilia.

Secondary causes

• Parasitic infestations: Infestations caused by parasites include ancylostomatidis, ascariasis, cysticercosis, echinococcosis (hydatid cyst), schistosomiasis, strongyloidiasis, trichinellosis, and visceral larva migrans (toxocariasis).
• Fungal and bacterial infections: Infections caused by fungi and bacteria include bronchopulmonary aspergillosis, chronic tuberculosis (rarely), coccidioidomycosis, disseminated histoplasmosis, and scarlet fever.
• Allergic disorders: Bronchial asthma, hay fever, Stevens-Johnson syndrome, medication and food allergic reactions, DRESS syndrome are examples of allergic illnesses.
• Skin diseases: Atopic dermatitis, eczema, pemphigus, Mycosis fungoides, and Sezary syndrome are skin illnesses.
• Host-versus-graft response
• Connective tissue disease: Diseases of the connective tissue include Chrug-Strauss syndrome and eosinophilic myalgia syndrome.
• Miscellaneous: pulmonary eosinophilia reactive, tropical eosinophilia, pancreatitis, eosinophilic gastroenteritis.

Reason for high Eosinophils counts

Eosinophils are a type of white blood cell that play a role in the body’s immune response to allergens and parasites. A high count of eosinophils, a condition called eosinophilia, may indicate an underlying health problem. Here are some possible reasons for a high eosinophil count:

1. Allergic reactions: Allergies to substances such as pollen, food, or medications can trigger the release of eosinophils and lead to a high eosinophil count.
2. Asthma: Asthma is a chronic respiratory condition that involves inflammation of the airways. Eosinophils are often involved in this inflammatory response, leading to a high eosinophil count.
3. Parasitic infections: Certain parasitic infections, such as roundworms or hookworms, can trigger a high eosinophil count.
4. Autoimmune disorders: Some autoimmune disorders, such as eosinophilic granulomatosis with polyangiitis (EGPA), can cause a high eosinophil count.
5. Skin conditions: Certain skin conditions, such as eczema, can cause a high eosinophil count.
6. Certain medications: Certain medications, such as antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), can cause a high eosinophil count as a side effect.
7. Blood disorders: Certain blood disorders, such as lymphoma or leukemia, can cause a high eosinophil count.

Reason for low Eosinophils counts

Eosinophils are a type of white blood cells that play a role in the body’s immune response to infections and inflammation. A low count of eosinophils, a condition called eosinopenia, may indicate an underlying health problem. However, eosinopenia itself is not a disease, but a symptom of an underlying condition.

Some of the conditions that can lead to low eosinophil count include:

1. Acute bacterial infections: Such as sepsis, bacterial pneumonia, and meningitis, can cause a temporary decrease in eosinophil count.
2. Certain medications: Such as corticosteroids, which are commonly used to treat inflammation and allergies, can suppress eosinophil production and lead to a low count.
3. Stress: Prolonged stress can decrease eosinophil count.
4. Certain cancers: Some cancers, such as leukemia and lymphoma, can lead to a low eosinophil count.
5. Overwhelming infections: Viral infections such as HIV, measles, mumps, and rubella, can cause a temporary decrease in eosinophil count.
6. Autoimmune disorders: Such as lupus and rheumatoid arthritis, can cause a low eosinophil count.
7. Parasitic infections: Such as hookworms, roundworms, and tapeworms, can cause a decrease in eosinophil count.
8. Congenital disorders: Rare congenital disorders, such as Job’s syndrome, can lead to a low eosinophil count.

FAQ

References

• Kovalszki A, Weller PF. Eosinophilia. Prim Care. 2016 Dec;43(4):607-617. doi: 10.1016/j.pop.2016.07.010. Epub 2016 Oct 14. PMID: 27866580; PMCID: PMC5293177.
• Kanuru S, Sapra A. Eosinophilia. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560929/
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