Granular Leukocytes

We will consider the granular leukocytes in order from most common to least common. All of these are produced in the red bone marrow and have a short lifespan of hours to days. They typically have a lobed nucleus and are classified according to which type of stain best highlights their granules (Figure 18.4.2).

The most common of all the leukocytes, neutrophils will normally comprise 50–70 percent of total leukocyte count. They are 10–12 µm in diameter, significantly larger than erythrocytes. They are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic). The granules are numerous but quite fine and normally appear light lilac. The nucleus has a distinct lobed appearance and may have two to five lobes, the number increasing with the age of the cell. Older neutrophils have increasing numbers of lobes and are often referred to as polymorphonuclear (a nucleus with many forms), or simply “polys.” Younger and immature neutrophils begin to develop lobes and are known as “bands.”

Neutrophils are rapid responders to the site of infection and are efficient phagocytes with a preference for bacteria. Their granules include lysozyme, an enzyme capable of lysing, or breaking down, bacterial cell walls; oxidants such as hydrogen peroxide; and defensins, proteins that bind to and puncture bacterial and fungal plasma membranes, so that the cell contents leak out. Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin. Low counts may be caused by drug toxicity and other disorders, and may increase an individual’s susceptibility to infection.

Eosinophils typically represent 2–4 percent of total leukocyte count. They are also 10–12 µm in diameter. The granules of eosinophils stain best with an acidic stain known as eosin. The nucleus of the eosinophil will typically have two to three lobes and, if stained properly, the granules will have a distinct red to orange color.

The granules of eosinophils include antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced by basophils and mast cells. Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat. Eosinophils are also capable of phagocytosis and are particularly effective when antibodies bind to the target and form an antigen-antibody complex. High counts of eosinophils are typical of patients experiencing allergies, parasitic worm infestations, and some autoimmune diseases. Low counts may be due to drug toxicity and stress.

Basophils are the least common leukocytes, typically comprising less than one percent of the total leukocyte count. They are slightly smaller than neutrophils and eosinophils at 8–10 µm in diameter. The granules of basophils stain best with basic (alkaline) stains. Basophils contain large granules that pick up a dark blue stain and are so common they may make it difficult to see the two-lobed nucleus.

In general, basophils intensify the inflammatory response. They share this trait with mast cells. In the past, mast cells were considered to be basophils that left the circulation. However, this appears not to be the case, as the two cell types develop from different lineages.

The granules of basophils release histamines, which contribute to inflammation, and heparin, which opposes blood clotting. High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism. Low counts are associated with pregnancy, stress, and hyperthyroidism.

Agranular Leukocytes

Agranular leukocytes contain smaller, less-visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes (see Figure 1; chapter 18.3).

Lymphocytes are the only formed element of blood that arises from lymphoid stem cells. Although they form initially in the bone marrow, much of their subsequent development and reproduction occurs in the lymphatic tissues. Lymphocytes are the second most common type of leukocyte, accounting for about 20–30 percent of all leukocytes, and are essential for the immune response. The size range of lymphocytes is quite extensive, with some authorities recognizing two size classes and others three. Typically, the large cells are 10–14 µm and have a smaller nucleus-to-cytoplasm ratio and more granules. The smaller cells are typically 6–9 µm with a larger volume of nucleus to cytoplasm, creating a “halo” effect. A few cells may fall outside these ranges, at 14–17 µm. This finding has led to the three size range classification.

The three major groups of lymphocytes include natural killer cells, B cells, and T cells. Natural killer (NK) cells are capable of recognizing cells that do not express “self” proteins on their plasma membrane or that contain foreign or abnormal markers. These “nonself” cells include cancer cells, cells infected with a virus, and other cells with atypical surface proteins. Thus, they provide generalized, nonspecific immunity. The larger lymphocytes are typically NK cells.

B cells and T cells, also called B lymphocytes and T lymphocytes, play prominent roles in defending the body against specific pathogens (disease-causing microorganisms) and are involved in specific immunity. One form of B cells (plasma cells) produces the antibodies or immunoglobulins that bind to specific foreign or abnormal components of plasma membranes. This is also referred to as humoral (body fluid) immunity. T cells provide cellular-level immunity by physically attacking foreign or diseased cells. A memory cell is a variety of both B and T cells that forms after exposure to a pathogen and mounts rapid responses upon subsequent exposures. Unlike other leukocytes, memory cells live for many years. B cells undergo a maturation process in the bone marrow, whereas T cells undergo maturation in the thymus. This site of the maturation process gives rise to the name B and T cells. The functions of lymphocytes are complex and will be covered in detail in the chapter covering the lymphatic system and immunity. Smaller lymphocytes are either B or T cells, although they cannot be differentiated in a normal blood smear.

Abnormally high lymphocyte counts are characteristic of viral infections as well as some types of cancer. Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids.

Monocytes originate from myeloid stem cells. They normally represent 2–8 percent of the total leukocyte count. They are typically easily recognized by their large size of 12–20 µm and indented or horseshoe-shaped nuclei. Macrophages are monocytes that have left the circulation and phagocytize debris, foreign pathogens, worn-out erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release antimicrobial defensins and chemotactic chemicals that attract other leukocytes to the site of an infection. Some macrophages occupy fixed locations, whereas others wander through the tissue fluid.

Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukemia and other chronic diseases. Abnormally low counts are typically caused by suppression of the bone marrow.