White Blood Cells - Guardians of Health

Introduction

The human immune system is a biological processing network that protects from diseases. It detects and responds to various pathogens distinguishing them from healthy tissue. White blood cells (WBC) are a group of circulating cells in the body. Their average concentration in blood is 4000 to 10,000 per microliter.

During an infection, the body makes more WBCs to fight the bacteria, viruses, or other foreign substances. However, other diseases can cause a decreased WBC count. These include certain cancers, human immunodeficiency virus-acquired immunodeficiency syndrome(HIV-AIDS), and chemotherapy.

How Are the White Blood Cells Classified?

WBCs are classified based on the presence of specific granules in their cytoplasm into the following.

Granulocytes: Neutrophils, basophils, and eosinophils are granulocytes. These cells have specific granules containing substances unique to the cell function. Granulocytes can be distinguished from each other by the nuclear structure, size, and staining of the granules.

• Neutrophils are 12 to 15 micrometers (µm) in diameter and have multilobed nuclei joined by thin strands. Hence, they are also called polymorphonuclear leukocytes (PMNLs). Neutrophils contain specific granules in the cytoplasm (a gel-like structure that fills the cell) that give it a pale pink color. These cells have short life spans (a few days), and after their death, they are removed by macrophages (a large WBC).

• Eosinophils have a bi-lobed nucleus (resembles a spectacle) with large cytoplasmic specific granules.

• Basophils are 12 to15 µm in diameter, and have S-shaped nuclei, and contain cytoplasmic specific granules. The granules contain heparin and sulfated glycosaminoglycans (large sugar compounds).

Agranulocytes: Lymphocytes and monocytes comprise agranulocytes. Agranulocytes lack specific granules. Monocytes are precursor cells for macrophages, osteoclasts (a type of bone cell), and microglial cells (immune cells in the brain). These cells constitute four to eight percent of WBCs and have large nuclei that are C- shaped. There is abundant cytoplasm, and the non-specific granules give the cytoplasm bluish-gray color under a light microscope.

Lymphocytes constitute approximately 25 percent WBCs and have spherical nuclei. They are of varying sizes. The small lymphocytes are similar in size to a red blood cell (RBC), have spherical nuclei, and have scant cytoplasm. The larger lymphocytes (activated lymphocytes) are 9 to 18 µm in diameter. Their major groups are B lymphocytes and T lymphocytes.

What Are the Various Functions of the White Blood Cells?

All WBCs have immune system functions. Diapedesis (also called extravasation) is common to all WBCs. WBC migration to sites of injury or infection is mediated by patterns represented by microbes and damaged tissue. Local inflammatory cells (macrophages and mast cells) detect these patterns and release cytokines for WBCs to migrate out of circulation. Histamine and heparin (inflammatory mediators) released by masts cell aid in opening junctions between the capillary endothelial cells (cells that line blood vessels). Furthermore, endothelial cells secrete molecules that aid WBC adhesion, rolling, arrest, and migration into the affected tissues. However, the specific roles and functions differ for each type of WBC.

1. Neutrophils: Neutrophils comprise 50 to 70 percent of circulating WBCs and represent the body's first line of defense (also called the policeman of the blood). They are involved in the acute (immediate) inflammatory response to bacterial infection. They also remove bacteria by phagocytosis (cell-eating). They are also the most abundant cells to arrive at the site of infection. They then undergo diapedesis. Further, they recognize foreign antigens on bacteria, infectious agents, dead cells, and debris through various membrane receptors. Specific granules containing myeloperoxidase (an enzyme) fuse with the lysosome (a cell organ that produces digestive enzymes), resulting in the degradation of bacteria by reactive oxygen species (ROS; reactive molecules) generation.

2. Basophils: Basophils make up less than one percent of all WBcs. Their primary function is aiding in inflammation and allergic reaction. Basophils have a high affinity for binding IgE antibodies (defense proteins of the body). Allergens binding to the IgE on the basophils surface results in the degradation and release of inflammatory mediators (histamine, platelet-activating factor, and phospholipase A). These agents cause the symptoms of allergies, hypersensitivity reactions, and anaphylaxis. One must note that basophils have almost no phagocytic abilities.

3. Eosinophils: Eosinophils comprise approximately 1 to 4 percent of the WBCs. They are involved in chronic inflammation, allergic reactions, and defense against parasites. They also modulate the effects of inflammatory mediators. Eosinophils fight parasitic infections by releasing specific granules. Out of the granules, the major basic protein is particularly toxic against helminths (parasitic worms). Lastly, they have phagocytic activity similar to neutrophils and basophils. However, they commonly clear antigen-antibody complexes (molecules formed due to the interaction of an antibody and a foreign protein, the antigen).

4. Monocytes: Monocytes comprise about two to eight percent of WBCs. They differentiate and become functional only after they leave the blood. Then, they differentiate into specific cells in an organ, such as macrophages (in the lung, connective tissue and lymphatic tissues, and bone), osteoclasts (bone), and Kupffer cells (liver). As a result, they phagocytose bacteria, cells, and debris.

5. Lymphocytes: Lymphocytes are agranulocytes and consist of 20 to 40 percent of the WBC count. They are a part of the adaptive immune system (specific immunity formed after exposure to a pathogen). Also, lymphocytes are circulating cells that develop the ability to recognize and react to antigens.

What Is the Clinical Significance of White Blood Cells?

Clinically, the complete blood count (CBC) test measures WBCs. A CBC is done to provide insight into the disease process. An associated test with the CBC is a differential WBC count (which refers to the relative amount of WBC types as a percentage of the total number of WBCs). A decrease below the normal range of WBCs is leukopenia. On the contrary, anything that exceeds this range is called leukocytosis. A peripheral blood smear (PBS; allows for the microscopic analysis of the blood circulating throughout the body) is an additional optional test. A PBS is helpful in leukopenia, leukemia (blood cancer), or lymphoma (lymphatic system cancer).

• Leukopenia: In this condition, the WBC counts are lower than average. Leukopenia can occur with viral infections, chemotherapy, and other diseases, such as systemic lupus erythematosus (SLE).

• Leukocytosis: It occurs when the WBC counts (primarily neutrophils) are higher than normal. It is also accompanied by an increase in immature cells in the blood. Leukocytosis is commonly a sign of inflammatory response such as infection, but it can also occur in parasitic infections or leukemia, and stress.

Conclusion

White blood cells are an integral part of the immune system that protects the body from infection. These cells circulate throughout the bloodstream and tissues to respond to injury or illness by attacking unknown organisms entering the body. Therefore, although white blood cells account for only about one percent of the blood, their impact is substantial