WHITE BLOOD CELLS



WHITE BLOOD CELLS

White blood cells or leukocytes, are cells of the immune system involved in defending the body against both infectious disease, sickness and the bacteria in your body. The white blood cells are continually on the lookout for signs of disease. When a germ does appear, the white blood cells have a variety of ways by which they can attack. Some will produce protective antibodies that will overpower the germ. Others will surround and devour the bacteria.

The white blood cells have a rather short life cycle, living from a few days to a few weeks. A drop of blood can contain anywhere from 7,000 to 25,000 white blood cells at a time. If an invading infection fights back and persists, that number will significantly increase. A consistently high number of white blood cells is a symptom of Leukemia, a cancer of the blood. A Leukemia patient may have as many as 50,000 white blood cells in a single drop of blood. White blood cells (WBCs), or leukocytes, are a part of the immune system and help our bodies fight infection. They circulate in the blood so that they can be transported to an area where an infection has developed. In a normal adult body there are 4,000 to 10,000 (average 7,000) WBCs per microliter of blood. When the number of WBCs in your blood increases, this is a sign of an infection somewhere in your body.

Here are the six main types of WBCs and the average percentage of each type in the blood:

• Neutrophils - 58 percent

• Eosinophils - 2 percent

• Basophils - 1 percent

• Bands - 3 percent

• Monocytes - 4 percent

• Lymphocytes - 4 percent

Most WBCs (neutrophils, eosinophils, basophils and monocytes) are formed in the bone marrow. Neutrophils, eosinophils and basophils are also called granulocytes because they have granules in their cells that contain digestive enzymes. Basophils have purple granules, eosinophils have orange-red granules and neutrophils have a faint blue-pink color. When a granulocyte is released into the blood, it stays there for an average of four to eight hours and then goes into the tissues of the body, where it lasts for an average of four to five days. During a severe infection, these times are often shorter.

Neutrophils are the one of the body's main defenses against bacteria. They kill bacteria by actually ingesting them (this is called phagocytosis). Neutrophils can phagocytize five to 20 bacteria in their lifetime. Neutrophils have a multi-lobed, segmented or polymorphonuclear nucleus and so are also called PMNs, polys or segs. Bands are immature neutrophils that are seen in the blood. When a bacterial infection is present, an increase of neutrophils and bands are seen.

Eosinophils kill parasites and have a role in allergic reactions.

Basophils are not well understood, but they function in allergic reactions. They release histamine (which causes blood vessels to leak and attracts WBCs) and heparin (which prevents clotting in the infected area so that the WBCs can reach the bacteria).

Monocytes enter the tissue, where they become larger and turn into macrophages. There they can phagocytize bacteria (up to 100 in their lifetime) throughout the body. These cells also destroy old, damaged and dead cells in the body. Macrophages are found in the liver, spleen, lungs, lymph nodes, skin and intestine. The system of macrophages scattered throughout the body is called the reticuloendothelial system. Monocytes stay in the blood for an average of 10 to 20 hours and then go into the tissues, where they become tissue macrophages and can live for months to years.

Neutrophils and monocytes use several mechanisms to get to and kill invading organisms. They can squeeze through openings in blood vessels by a process called diapedesis. They move around using ameboid motion. They are attracted to certain chemicals produced by the immune system or by bacteria and migrate toward areas of higher concentrations of these chemicals. This is called chemotaxis. They kill bacteria by a process called phagocytosis, in which they completely surround the bacteria and digest them with digestive enzymes.

NEUTROPHILS

Neutrophils are the most common granulocyte. They have segmented nuclei, typically with 2 to 5 lobes connected together by thin strands of chromatin which can be difficult to see; the cell may thus appear to have multiple nuclei. The nuclear chromatin is condensed into coarse clumps. Small numbers of immature neutrophils or band form neutrophils may be seen in a blood smear. These are incompletely segmented and often have a 'C-shaped' nucleus.

The cytoplasm of neutrophils contains three types of granule.

Primary granules are non-specific and contain lysosomal enzymes, defensins, and some lysozyme. The granules are similar to lysosomes. They stain aviolet colour when prepared with Wright's stain which is commonly used in studying the blood. The enzymes produce hydrogen peroxide which is a powerful anti-bacterial agent.

Secondary granules are specific to neutrophils and stain light pink ('neutral stain'). They contain collagenase, to help the cell move through connective tissue, and lactoferrin, which is toxic to bacteria and fungi.

Tertiary granules have only recently been recognised. It is thought that they produce proteins which help the neutrophils to stick to other cells and hence aid the process of phagocytosis.

Once in the area of infection neutrophils respond to chemicals (called chemotaxins which are released by bacteria and dead tissue cells) and move towards the area of highest concentration. Here they begin the process of phagocytosis in which they engulf the offending cells and destroy them with their powerful enzymes. Because this process consumes so much energy the neutrophils glycogen reserves are soon depleted and they die soon after phagocytosis. When the cells die their contents are released and the remnants of their enzymes cause liquefaction of closely adjacent tissue. This results in an accumulation of dead neutrophils, tissue fluid and abnormal materials known as pus.

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EOSINOPHILS

Eosinophils have a bi-lobed nucleus as shown above in a slide of a stained blood smear.

They increase greatly in many types of parasitic infection and defence against the larvae of parasitic worms and unicellular organisms seems to be one of their primary functions. The granules of eosinophils contain a substance called MBP (major basic protein) which is toxic to many parasitic larvae. Eosinophils also have surface receptors for the antibody immunoglobulin E (IgE). These receptors are not found in neutrophils and again this is thought to reflect their role in parasitic infection.

They also increase in number in some allergic states. For example their numbers increase in the nasal and bronchial mucosal linings in hay fever and asthma and in some adverse drug reactions. It is thought that they may neutralise the effect of histamine.

Eosinophils also have a marked diurnal variation with their numbers being highest in the morning and lowest in the afternoon although why this is the case is at present unclear.

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BASOPHILS

Basophils are the least common of the white blood cells. They are characterised by their large cytoplasmic granules which obscure the nucleus in stained preparations as shown above. They have many similarities with mast cells and actually become mast cells on leaving the blood and entering surrounding tissues.

Mast cells are widely distributed throughout the body and are commonly found in close proximity to the walls of small blood vessels.

Both basophils and mast cells have highly specific receptors for IgE produced in response to various allergens.

Response to specific allergens is rapid and results in expulsion of the cells granular contents which contain histamines and other vasodilating agents. This results in the reaction known as immediate hypersensitivity. This can result in hay fever, some forms of asthma, urticaria (nettle rash) and most seriously anaphylactic shock.

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MONOCYTES

Monocytes are the largest cell type seen in blood smears. Their nuclei are not multilobular like granulocytes, but may be deeply indented or U-shaped, with reticular-appearing chromatin. The cytoplasm of monocytes contains numerous lysosomal granules which give it a uniform grayish-blue "ground-glass" appearance. They form part of a cell network known as the monocyte-macrophage system. This comprises bone marrow precursor cells (monoblasts and promonocytes), circulating monocytes and both free and fixed tissue macrophages.

Monocytes eventually leave the bloodstream to become tissue macrophages which remove dead cell debris as well as attacking organisms such as Tubercule Bacilli (which causes TB) and some fungi. Neither of these can be dealt with effectively by the neutrophils. Unlike neutrophils monocytes are able to reolace their lysosomal contents and are thought to have a much longer active life.

Cells which derive from monocytes include the

• Kupffer cells of the liver

• sinus lining cells of the spleen and lymph nodes

• pulmonary alveolar macrophages

• free macrophages in the synovial, pleural and peritoneal fluid

• dendritic antigen presenting cells

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LYMPHOCYTES

These are the most numerous white blood cell in young children and the second most numerous in older children and adults.

Their numbers increase in response to viral infections.

Lymphocytes are distinguished by having a deeply staining nucleus which may be eccentric in location, and a relatively small amount of cytoplasm. The small ring of cytoplasm contains numerous ribosomes and stains blue. Small numbers of lysosomal granules may also be seen in the cytoplasm of some lymphocytes.

In this image, a lymphocyte and a dumbbell-shaped Red Blood Cell (RBC) can be seen in the lumen of a small blood vessel. Note the pseudopodia and the small amount of cytoplasm of the lymphocyte.

The two major types of lymphocyte found in the blood are B-lymphocytes and T-lymphocytes. Both have different but linked roles in the generation of specific immune response. The small mature lymphocytes circulating in the blood are constantly sampling their environment for foreign materials. Their role is discussed more fully in the sessions on the immune system.

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Increased numbers of white blood cells appear in the peripheral blood in a variety of disorders.

The most important and most life threatening disorders are the leukaemias. Here there is a malignant proliferation of white cell precursors in the bone marrow. This produces vast numbers of white blood cells and their precursors which then spill over into the the blood stream. The various types of leukaemia are classified according to the cell line involved (granulocytic, monocytic, lymphocytic etc.) and also according to their degree of malignancy.

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