Basophils are a type of white blood cells. Basophils are the least common of the granulocytes, representing about 0.5 to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They can perform phagocytosis (cell eating), produce histamine and serotonin that induce inflammation, and heparin that prevents blood clotting. It used to be thought that basophils that have migrated from blood into their resident tissues (connective tissue) are known as mast cells, but this is no longer thought to be the case.

Basophils were discovered in 1879 by German physician Paul Ehrlich, who one year earlier had found a cell type present in tissues that he termed "mastzellen" (now mast cells). Ehrlich received the 1908 Nobel Prize in Physiology or Medicine for his discoveries.

The name comes from the fact that these leukocytes are basophilic, i.e., they are susceptible to staining by basic dyes, as shown in the picture.

Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN, PML, or PMNL) because of the varying shapes of the nucleus, which is usually lobed into three segments. This distinguishes them from the mononuclear agranulocytes. In common parlance, the term "polymorphonuclear leukocyte" often refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow.

There are four types of granulocytes:

- Basophils

- Eosinophils

- Neutrophils

- Mast cells

Their names are derived from their staining characteristics; for example, the most abundant granulocyte is the neutrophil granulocyte, which has neutrally staining cytoplasmic granules.

Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.

They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.

The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.

Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.

Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.

Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.

These cells are eosinophilic or "acid-loving" due to their large acidophilic cytoplasmic granules, which show their affinity for acids by their affinity to coal tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after staining with eosin, a red dye, using the Romanowsky method. The staining is concentrated in small granules within the cellular cytoplasm, which contain many chemical mediators, such as eosinophil peroxidase, ribonuclease (RNase), deoxyribonucleases (DNase), lipase, plasminogen, and major basic protein. These mediators are released by a process called degranulation following activation of the eosinophil, and are toxic to both parasite and host tissues.

In normal individuals, eosinophils make up about 1–3% of white blood cells, and are about 12–17 micrometres in size with bilobed nuclei. While they are released into the bloodstream as neutrophils are, eosinophils reside in tissue They are found in the medulla and the junction between the cortex and medulla of the thymus, and, in the lower gastrointestinal tract, ovary, uterus, spleen, and lymph nodes, but not in the lung, skin, esophagus, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease. For instance, patients with eosinophilic asthma have high levels of eosinophils that lead to inflammation and tissue damage, making it more difficult for patients to breathe. Eosinophils persist in the circulation for 8–12 hours, and can survive in tissue for an additional 8–12 days in the absence of stimulation. Pioneering work in the 1980s elucidated that eosinophils were unique granulocytes, having the capacity to survive for extended periods of time after their maturation as demonstrated by ex-vivo culture experiments.

When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers (µm) in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 µm.

With the eosinophil and the basophil, they form the class of "polymorphonuclear cells", named for the nucleus' multilobulated shape (as compared to lymphocytes and monocytes, the other types of white cells). The nucleus has a characteristic lobed appearance, the separate lobes connected by chromatin. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent. The cytoplasm also contains about 200 granules, of which a third are azurophilic.

Neutrophils are sexually dimorphic. Neutrophils from women exhibit a small additional X chromosome structure, known as a "neutrophil drumstick".

Neutrophils will show increasing segmentation (many segments of nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal, and occurs in some disorders, most notably vitamin B deficiency. This is noted on a manual review of the blood smear, and is positive when most or all of the neutrophils have 5 or more segments.

Neutrophils are the most abundant white blood cells in humans (approximately 10 are produced daily); they account for approximately 50–70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 x 10/L is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal. A report may divide neutrophils into segmented neutrophils and bands.

When circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or amoeba-like and can extend pseudopods as they hunt for antigens.

Neutrophils have a preference to engulf refined carbohydrates (from ingested glucose, fructose, sucrose, honey and orange juice) over bacteria. In 1973 Sanchez et al. found that the neutrophil phagocytic capacity to engulf bacteria is affected when simple sugars are digested, and that fasting strengthens the neutrophils' phagocytic capacity to engulf bacteria. However, the digestion of normal starches has no effect. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars, neutrophils engulf some types of sugar preferentially.

Basophils contain large cytoplasmic granules which obscure the cell nucleus under the microscope when stained. However, when unstained, the nucleus is visible and it usually has two . The mast cell, another granulocyte, is similar in appearance and function. Both cell types store histamine, a chemical that is secreted by the cells when stimulated. However, they arise from different branches of hematopoiesis, and mast cells usually do not circulate in the blood stream, but instead are located in connective tissue. Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed.

An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophilia, and is typically seen in people with a parasitic infestation of the intestines; autoimmune and collagen vascular disease (such as rheumatoid arthritis) and Systemic lupus erythematosus; malignant diseases such as eosinophilic leukemia, clonal hypereosinophilia, and Hodgkin's disease; lymphocyte-variant hypereosinophilia; extensive skin diseases (such as exfoliative dermatitis); Addison's disease and other causes of low corticosteroid production (corticosteroids suppress blood eosinophil levels); reflux esophagitis (in which eosinophils will be found in the squamous epithelium of the esophagus) and eosinophilic esophagitis; and with the use of certain drugs such as penicillin. But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the Toxic Oil Syndrome in Spain in 1981.

Eosinophils play an important role in asthma as the number of accumulated eosinophils corresponds to the severity of asthmatic reaction. Eosinophilia in mice models are shown to be associated with high interleukin-5 levels. Furthermore, mucosal bronchial biopsies conducted on patients with diseases such as asthma have been found to have higher levels of interleukin-5 leading to higher levels of eosinophils. The infiltration of eosinophils at these high concentrations causes an inflammatory reaction. This ultimately leads to airway remodelling and difficulty of breathing.

Eosinophils can also cause tissue damage in the lungs of asthmatic patients. High concentrations of eosinophil major basic protein and eosinophil-derived neurotoxin that approach cytotoxic levels are observed at degranulation sites in the lungs as well as in the asthmatic sputum.

Acute basophilic leukemia is a rare form of acute myeloid leukemia where blasts are accompanied by abnormal basophils in all stages of differentiation. It would most likely be classified as M0 without electron microscopic confirmation of basophil lineage.

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.

Differentiated (basophilic granules by light microscopy) and poorly differentiated cases ; Majority are poorly differentiated. MPO negative by light microscopy; granules positive in a speckled pattern by electron microscopy. Myeloid antigens are expressed. Diagnosis of poorly differentiated cases made by electron microscopy. May manifest basophil and mast cell granules by EM. Cytogenetically heterogeneous but frequently associated with Philadelphia chromosome. There is no clinically distinguishing features but may be more common in children and young adults and carry a poor prognosis.

Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs "de novo" but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

Basophilia as an isolated finding is uncommon. However it is a common feature of myeloproliferative disorders and particularly prominent in chronic myelogenous leukemia.

Conditions Associated with Increased Numbers of Blood Basophils

- Allergy or inflammation

1. Ulcerative colitis

2. Drug, food, inhalant hypersensitivity

3. Erythroderma, urticaria

4. Juvenile rheumatoid arthritis

- Endocrinopathy

1. Diabetes mellitus

2. Estrogen administration

3. Hypothyroidism (myxedema)

- Infection

1. Chicken pox

2. Influenza

3. Smallpox

4. Tuberculosis

- Iron deficiency

- Exposure to ionizing radiation

- Neoplasia

1. "Basophilic leukemia" (see text)

- Myeloproliferative neoplasms (especially chronic myelogenous leukemia; also polycythemia vera, primary myelofibrosis, essential thrombocythemia)

- Carcinoma

Basophilia is a condition where the basophil quantity is abnormally elevated (more than 10 basophils per liter of blood). Basophilia is associated with pruritus (itching) due to the release of histamine.

Myelofibrosis, also known as osteomyelofibrosis, is a relatively rare bone marrow cancer. It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.

The term "myelofibrosis" alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (cIMF); the terms idiopathic and primary mean that in these cases the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously. The terms agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) are also used to refer to primary myelofibrosis.

The primary sign of myelofibrosis is reactive bone marrow fibrosis, but it is often accompanied by:

- Abdominal fullness related to an enlarged spleen (splenomegaly).

- Bone pain

- Bruising and easy bleeding due to inadequate numbers of platelets

- Cachexia (loss of appetite, weight loss, and fatigue)

- Enlargement of both the liver and spleen

- Fatigue

- Gout and high uric acid levels

- Increased susceptibility to infection, such as pneumonia

- Pallor and shortness of breath due to anemia

- In rarer cases, a raised red blood cell volume

- Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.

A typical allergic reaction to alpha-gal has a delayed onset, occurring 3–8 hours after the consumption of mammalian meat products, instead of the typical rapid onset with most food allergies. After the delayed onset, the allergic response is typical of most food allergies, and especially an IgE mediated allergy, including severe whole-body itching, hives, angioedema, gastrointestinal upset, and possible anaphylaxis. In 70% of cases the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.

Alpha-gal allergies are the first food allergies to come with the possibility of delayed anaphylaxis. It is also the first food-related allergy to be associated with a carbohydrate, rather than a protein.

Alpha-gal allergy, also known as meat allergy or Mammalian Meat Allergy (MMA), is a reaction to galactose-alpha-1,3-galactose (alpha-gal), whereby the body is overloaded with immunoglobulin E (IgE) antibodies on contact with the carbohydrate. The alpha-gal molecule is found in all mammals apart from Old World monkeys and the apes, which include humans. Anti-Gal is a human natural antibody which interacts specifically with the mammalian carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R, termed, the alpha-galactosyl epitope. Whereas anti-Gal is abundant in humans, apes and Old World monkeys, it is absent from New World monkeys, prosimians and nonprimate mammals.

Bites from certain ticks, such as the lone star tick in the US, which can transfer this carbohydrate to the victim have been implicated in the development of this delayed allergic response which is triggered by the consumption of mammalian meat products. Despite myths to the contrary, an alpha-gal allergy does not require the afflicted to become a vegetarian, as poultry and fish do not trigger a reaction.

The allergy most often occurs in the central and southern United States, which corresponds to the distribution of the lone star tick. In the Southern United States, where the tick is most prevalent, allergy rates are 32% higher than elsewhere. However, as doctors are not required to report the number of patients suffering the alpha-gal allergies, the true number of affected individuals is unknown. While there is no known cure, symptoms of the allergy may recede over time. Some patients report observing symptoms for over 20 years.

The less-common signs and symptoms of Cushing's disease include the following:

- insomnia

- recurrent infection

- thin skin and stretch marks

- easy bruising

- weak bones

- acne

- balding (women)

- depression

- hip and shoulder weakness

- swelling of feet/legs

- diabetes mellitus

- erectile dysfunction

Common signs and symptoms of Cushing's disease include the following:

- weight gain

- high blood pressure

- poor short-term memory

- irritability

- excess hair growth (women)

- Impaired immunological function

- red, ruddy face

- extra fat around neck

- moon face

- fatigue

- red stretch marks

- poor concentration

- irregular menstruation