- Leukocytes play an important role in the normal functioning of the immune system.
- They protect the body against harmful diseases and foreign elements.
- White blood cells (WBCs) are more diverse in structure and cellular operation compared to red blood cells (RBCs).
What are leukocytes?
White blood cells or WBCs are also called as leukocytes. They are one of the important components of blood. Leukocytes play an important role in the normal functioning of the immune system. They protect the body against harmful diseases and foreign elements.
WBCs vs. RBCs
When compared to red blood cells (RBCs), leukocytes are colorless, which is why they are named as "white blood cells". Red blood cells (RBCs) are of one type, but white blood cells (WBCs) are of five types. Leukocytes are more diverse in structure and cellular operation, whereas red blood cells are specialized to perform a single function. Red blood cells do not contain a nucleus. On the other hand, white blood cells (WBCs) consist of organelles and nuclei.
The first description of leukocytes was reported by a French professor of medicine named Gabriel Andral and an English country practitioner named William Addison. They both concluded that the red and white globules of the blood were altered in diseases.
Primitive stem cells develop into leukocytes in the bone marrow. They undergo maturation and differentiation and then released into the bloodstream. The number of leukocytes circulating in the blood varies according to sex, age, time of the day, and activity.
There are various factors that can affect the count of these cells. They include stress in the body, whether these cells are consumed or being destroyed, or if they are sufficiently produced in the bone marrow.
Characteristics of Leukocytes
Erythrocytes, also called as red blood cells (RBCs), usually circulate within the blood vessels for a number of days. In the case of leukocytes, they use the bloodstream for transport from one place to another. These cells leave the capillaries through a process called as "emigration" or "diapedesis". In this process, the leukocytes squeeze themselves through adjacent cells in the blood cell wall. The same process happens when reaching a damaged or injured site. Once they reach their true destination, depending on their function, they are given distinct names such as "macrophage" or "microglia".
Chemotaxis is simply defined as a cellular movement, which can either be toward or away from chemical substances. White blood cells (WBCs) sometimes move toward the chemicals that draw them through signals. This is called as a positive chemotaxis. The same thing happens when leukocytes are attracted to the site of damage like a cut in the skin.
What is leukopoiesis?
Leukopoiesis is the development of leukocytes, which starts with a stem cell. There are two distinct lines of white blood cells: the lymphoid and myeloid lines. Leukopoiesis involves three maturation processes:
- Granulocyte maturation - First, a myeloid stem cell forms a progenitor cell. This cells further forms a myeloblast, which further differentiates into one of the three types of granulocyte (neutrophil, basophil, or eosinophil).
- Monocyte maturation - A myeloid stem cell forms a progenitor cell, which forms a monoblast instead of a myeloblast. The monoblast matures into a promonocyte, which ultimately forms a monocyte. Thus, monocytes are also derived from the myeloid stem cell.
- Lymphocyte maturation - A lymphoid cell differentiates itself along the lymphoid line into B-lymphoblast and T-lymphoblast cells. Some directly differentiate into natural killer (NK) cells. B-lymphoblasts ultimately mature into B-lymphocytes while T- lymphoblasts mature into T-lymphocytes.
The process of leukopoiesis is stimulated by colony–stimulating factors (CSFs), which are hormones produced by mature white blood cells (WBCs).
Different Types of Leukocytes
Leukocytes are divided into two major types: granulocytes and agranulocytes.
Granulocytes are leukocytes that have granules in their cytoplasm. They are also called as polymorphonuclear leukocytes. Under the microscope, granulocytes appear with a lobed nucleus. They usually have a short lifespan. Their classification is based on the type of stain that best stain their granules. There are three types of granular leukocytes: neutrophils, eosinophils, and basophils.
Neutrophils circulate in the blood for around 6-10 hours before they migrate into the extravascular tissue. The peripheral blood of adults contains an abundant amount of leukocytes. They are 10-12 μm in diameter. Neutrophils have numerous granules that show up most clearly when neutral stains are applied. Hence, they are named as "neutrophils". They have a lobed nucleus, which usually shows 2-5 five lobes.
As the cell ages, the number of lobes also increases. Older neutrophils are regarded as polymorphonuclear due to their increased number of lobes. The newly formed younger and immature neutrophils slowly begin to develop lobes known as bands. The majority of circulating neutrophils are polymorphonuclear (PMN) leukocytes.
Neutrophils have three types of granules:
- Primary granules (azurophilic) - this is found in all granulocytes. It contains myeloperoxidase, acid hydrolase, and defensin.
- Secondary granules (specific) - contains complement activators and enzymes.
- Tertiary granules - contain either phosphatases or metalloproteinases.
A high neutrophil count is often seen in burn patients and others who have high levels of stress. A low neutrophil count, on the other hand, may be due to drug toxicity and other health disorders.
Neutrophils are important when it comes to the defensive and reparative functions of the body.
Neutrophils secrete transcobalamin 1 or R binder protein, which is required for the proper absorption of vitamin B12 in the body.
Eosinophils represent a smaller percentage of the WBCs. They are rarely found in a blood smear. They are usually 10-12 μm in diameter. Eosinophils travel from the peripheral blood after a couple of hours and move into the loose connective tissue based on respiratory and gastrointestinal tracts. Their granules are stained best with eosin, which is an acidic stain. If stained properly, their granules have a distinct red or orange color. Their nucleus usually has 2-3 lobes.
Eosinophils have two types of granules. They are azurophilic and specific granules. Specific granules contain four proteins:
- Major basic protein (MBP)
- Eosinophil cationic protein (ECP)
- Eosinophil peroxidase (EPO)
- Eosinophil-derived neurotoxin (EDN)
The granules also contain histaminases, cathepsins, and collagenases.
Patients who are diagnosed with autoimmune diseases, allergies, and those with parasitic worm infections have an elevated eosinophil count in the blood. Patients who are under stress along with drug toxicity have low counts of eosinophil.
- Kills parasitic worms - Numerous eosinophils cluster around a large parasite. The molecules present in some eosinophil granules are toxic to parasitic worms. Hence, they are useful in killing parasites. Some studies have shown that eosinophils are also capable of destroying worms by secreting eosinophil cationic protein (ECP) and major basic protein (MBP).
- Phagocytosis - Eosinophils are capable of phagocytosis, especially when an antigen–antibody complex is formed.
- Allergy - The mast cells produce inflammatory chemicals called as histamines. Antihistamine granules are present in eosinophils, which counteract the activities of histamines. The products formed due to their breakdown further attract more eosinophils.
Basophils are the least common among leukocytes. They are slightly smaller than neutrophils and eosinophils. They are 8-10 μm in diameter. Their granules are best stained using basic stains. Basophils contain large granules, which reflect a dark blue color when stained. For this reason, it is quite difficult to view a bilobed nucleus.
The two types of basophil granules are azurophilic granules and specific granules. Specific granules contain heparin, histamine, leukotrienes, and some lysosomes. They are also derived from the same stem cell line as mast cells. They look very similar to mast cells but are not totally identical.
There is an elevated basophil count in the blood in cases of allergies, parasitic infections, and hypothyroidism. A low basophil count is often associated with pregnancy, stress, and hyperthyroidism.
- Prevents blood clot - Basophil secretes heparin, which prevents blood clotting.
- Tissue repair - When a tissue is damaged, basophils release histamine, which causes nearby capillaries to release plasma into the tissue spaces. Thus, nutrients and other compounds required for tissue repair flow into the injured area.
- Inflammatory response - There are IgE receptors on the surface membrane of basophils. When they are crosslinked by an antigen, it results in degranulation. The histamine present in basophil granules initiates an inflammation response. The release of histamine also plays an important role in allergic reactions such as hay fever and asthma.
Agranulocytes do not have small granules in their cytoplasm. Their nucleus is simple with an indentation, but without distinct lobes. They are of two types: monocytes and lymphocytes.
Lymphocytes are easily found in blood smears. Lymphocytes have three main types:
- B cells - develop in the bone marrow.
- T cells - produced in the bone marrow, but later move and mature in the thymus.
- Natural killer (NK) cells - develop both in the thymus and bone marrow.
Lymphocytes are resting blast forms, which have the capability to transform into active blasts when there is foreign invasion or infection. They undergo mitosis to produce effector and memory cells. Lymphocytes are found in the bloodstream and within the lymph node tissues, thymus gland, and spleen.
An elevated lymphocyte count is often associated with viral infections and some forms of cancer. A low lymphocyte count is associated with chronic illnesses and immunosuppression.
- Specific immunity - The B and T cells act as defense mechanisms against specific pathogens.
- Humoral immunity - When B-lymphocytes are properly stimulated, they manufacture antibodies or immunoglobulins, which bind to specific foreign or any abnormal-looking components of the plasma membrane. It protects the body from any foreign cells and substances.
- Cellular immunity - T-cells recognize and kill bacteria, virus-infected cells, and cancer cells.
- Innate immunity - The natural killer (NK) cells are capable of killing malignant tumors and other infected cells.
Monocytes are 12-20 μm in diameter. They can be easily recognized due to their large size and indented or horseshoe-shaped nuclei. They are known to circulate in the blood for 1-3 days before migrating into body tissues and transform into macrophages, detecting and destroying foreign bodies.
Some of the macrophages wander freely through the tissue fluid, whereas some stay at a fixed location. Medical conditions such as tuberculosis, fungal infections, and some forms of leukemia are all associated with high counts of monocytes. Bone marrow suppression is associated with very low counts of monocytes.
- Housekeeping functions - Monocytes are capable enough to remove any dead cells or debris from the site of infection or damaged tissue. They can destroy senescent red blood cells. They also synthesize proteins including prostaglandins, transferrin, coagulation factors, and growth factors. A storage pool of iron for erythropoiesis is also maintained.
- Innate immunity - Macrophages recognize bacterial pathogens and phagocytize foreign pathogens. Macrophages are known to release nitric oxide, which is cytotoxic against viruses, bacteria, fungi, and protozoa. They are thought to be the second line of defense against microbial invasions.
- Attract leukocytes - Certain chemotactic chemicals are released by macrophages, which also attracts the other leukocytes to the affected region.
- Inflammatory response - They also have an important role in responding back to inflammatory-related problems.
- Leukopenia - means that there is a decreased number of white blood cells (WBCs) in the blood. Most of the time, it is associated with a decrease in the neutrophil count.
- Leukocytosis - is the excessive proliferation of white blood cells (WBCs). It is usually a sign when the body responds to inflammation.
- Leukemia – is a type of cancer where the bone marrow produces abnormal white blood cells (WBCs). In chronic leukemia, mature leukocytes accumulate and they do not die. Acute leukemia involves an abundance of immature leukocytes. The white blood cells (WBCs) in both conditions do not function properly.
- Lymphoma - is cancer of the lymphatic system. A huge mass of malignant T and B lymphocytes get collected in the spleen, lymph nodes, tissues, and liver. These malignant lymphocytes do not function as needed. Thus, the patient becomes more vulnerable to developing any kind of infection.
Normal Leukocyte Count
Normally, 1 cu. mm of blood contains about 5,000-10,000 leukocytes. If the total number of WBCs is below 5,000 it is called leukopenia, and if the total number of WBCs is above 10,000 it is called leukocytosis.
- Adults: 4,000-11,000/mm3
- Newborns: 10,000-25,000/mm3
- Infants: 6,000-18,000/mm3
- Children: 5,000-15,000/mm3
Two methods are used to count white blood cells (WBCs). They are automated and non-automated cell counts. There can be some variations in the total number of white blood cells (WBCs) and its percentage since the body has to meet its changing defense needs.
The conditions that can alter the total white blood cell (WBC) count are as follows:
- Physical exercise
- After food intake
- Increased environmental temperature
- Sun exposure
- Acute bacterial infection
- Chronic infections
- Tissue injury
- Metabolic disorder
- Inflammatory disorder