Blood Cells- Definition and Types with Structure and Functions

Blood is a fluid connective tissue that consists of plasma and formed elements. Plasma is the liquid matrix of blood that contains water, proteins, electrolytes, hormones, and other substances. Formed elements are the cellular components of blood that include red blood cells (RBCs), white blood cells (WBCs), and platelets.

Blood cells are produced in the red bone marrow by a process called hematopoiesis. Hematopoiesis involves the differentiation of pluripotent stem cells into various types of blood cells. The production of blood cells is regulated by various factors such as hormones, cytokines, and feedback mechanisms.

Blood cells have different functions and characteristics depending on their type. RBCs are responsible for transporting oxygen and carbon dioxide between the lungs and the tissues. WBCs are involved in the immune system and protect the body from infections and foreign substances. Platelets are involved in hemostasis and help in blood clotting.

In this article, we will focus on the two main types of blood cells: RBCs and WBCs. We will discuss their structure, function, and classification in detail. We will also learn about the different types of WBCs and their roles in immunity.

Red blood cells (RBCs) or erythrocytes are the most abundant type of blood cells in the human body. They are responsible for transporting oxygen and carbon dioxide between the lungs and the tissues. RBCs have a unique shape and structure that allow them to perform their function efficiently and adapt to different conditions in the blood vessels.

Shape of Erythrocytes

RBCs have a biconcave discoid shape, which means they are flattened and have a concave center on both sides. This shape gives them a large surface area to volume ratio, which facilitates the diffusion of gases across their membrane. It also makes them flexible and deformable, which enables them to squeeze through narrow capillaries and bend around corners without breaking.

RBCs are anucleate, which means they lack a nucleus and other organelles. This allows them to save space and carry more hemoglobin, the protein that binds oxygen and carbon dioxide. Hemoglobin accounts for about 95% of the dry weight of RBCs and gives them their characteristic red color. Hemoglobin consists of four polypeptide chains, each with a heme group that contains an iron atom. Each iron atom can bind one molecule of oxygen or carbon dioxide, so one hemoglobin molecule can carry up to four molecules of gas.

The membrane of RBCs is composed of a phospholipid bilayer with embedded proteins. Some of these proteins are involved in transporting ions and maintaining the osmotic balance of the cells. Others are glycoproteins that serve as antigens, which determine the blood type of an individual. The membrane also contains a cytoskeleton, which is a network of proteins that provides mechanical support and shape stability to the cells. The main components of the cytoskeleton are spectrin, actin, ankyrin, and band 3.

The primary function of RBCs is to transport oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs. This is achieved by the reversible binding of these gases to hemoglobin. When RBCs reach the lungs, they encounter a high concentration of oxygen and a low concentration of carbon dioxide. This causes hemoglobin to release carbon dioxide and bind oxygen. The oxygenated hemoglobin gives RBCs a bright red color and is called oxyhemoglobin. When RBCs reach the tissues, they encounter a low concentration of oxygen and a high concentration of carbon dioxide. This causes hemoglobin to release oxygen and bind carbon dioxide. The deoxygenated hemoglobin gives RBCs a dark red color and is called deoxyhemoglobin.

Another function of RBCs is to maintain the acid-base balance of the blood by acting as buffers. Hemoglobin can bind hydrogen ions (H+) and bicarbonate ions (HCO3-) in addition to oxygen and carbon dioxide. This helps to regulate the pH of the blood, which is normally around 7.4.

RBCs also play a role in immune defense by carrying antibodies on their surface. Antibodies are proteins produced by B lymphocytes that recognize and bind to foreign antigens. When RBCs encounter antigens that match their antibodies, they agglutinate or clump together, forming visible clots. This helps to prevent the spread of infection and facilitates its removal by phagocytic cells.

Lifespan and Production of Erythrocytes

RBCs have a lifespan of about 120 days in circulation. During this time, they undergo wear and tear due to mechanical stress and oxidative damage. They also lose some of their membrane components and hemoglobin molecules through a process called senescence. As they age, they become less flexible and more fragile, making them prone to rupture or hemolysis.

RBCs are produced in the red bone marrow by a process called erythropoiesis. This process involves several stages of differentiation from pluripotent stem cells to mature erythrocytes. The rate of erythropoiesis is regulated by a hormone called erythropoietin (EPO), which is secreted by the kidneys in response to low oxygen levels in the blood. EPO stimulates the proliferation and maturation of erythroid progenitor cells in the bone marrow.

When RBCs die or are destroyed, they are removed from circulation by macrophages in the spleen, liver, and bone marrow. These phagocytic cells break down hemoglobin into its components: iron, heme, and globin. Iron is recycled back to the bone marrow for new hemoglobin synthesis. Heme is converted into bilirubin, which is excreted in bile by the liver. Globin is degraded into amino acids, which are reused for protein synthesis or metabolized for energy.

White blood cells (WBC) or leukocytes are a heterogeneous group of nucleated cells that are found in the blood that are primarily involved in the various activities related to immunity .

The normal concentration of WBCs in human blood varies between 4000 and 10,000 per microliter .

These cells play an essential role in phagocytosis and immunity and therefore in defense against infection .

Leukocytes are separated into two major groups; granulocytes and agranulocytes, based on the density of their cytoplasmic granules .

Granulocytes are a group of white blood cells that are characterized by the presence of cytoplasmic granules. They include neutrophils, eosinophils, and basophils. They are involved in killing bacteria, parasites, allergens, and other foreign substances .

Agranulocytes lack specific granules but do contain some azurophilic granules (lysosomes). They include lymphocytes and monocytes. They are involved in producing antibodies, regulating immune responses, and destroying infected or abnormal cells .

Granulocytes are a group of white blood cells that are characterized by the presence of cytoplasmic granules. All granulocytes are differentiated cells with a life span of only a few days. The cell contains Golgi complexes and rough ER that are poorly developed, with few mitochondria mainly needed for glycolysis to meet their energy needs. Granulocytes are further divided into eosinophils, neutrophils, and basophils depending on their reaction to different dyes.

• Eosinophils are granulocytes with a bilobed nucleus that can be differentiated from other leukocytes based on the presence of abundant large, acidophilic specific granules typically staining pink or red. Eosinophils are relatively less numerous than neutrophils, constituting only 1%-4% of total leukocytes. Ultrastructurally the eosinophilic specific granules are seen to be oval in shape, with flattened crystalloid cores containing major basic proteins. Eosinophils are particularly abundant in the connective tissue of the intestinal lining and at sites of chronic inflammation, such as lung tissues of asthma patients. Eosinophils also modulate inflammatory responses by releasing chemokines, cytokines, and lipid mediators, with an important role in the inflammatory response triggered by allergies.

• Basophils are blood cells in which the nucleus is divided into two irregular lobes, with specific cytoplasmic granules (0.5 μm in diameter) that typically stain purple with the basic dyes. The granules are fewer, larger, and more irregularly shaped than the granules of other granulocytes. Basophils are also 12-15 μm in diameter but make up less than 1% of circulating leukocytes and are therefore are difficult to find in normal blood smears. The strong basophilia of the granules is due to the presence of heparin and other sulfated GAGs. Basophilic granules also contain much histamine and various other mediators of inflammation, including platelet-activating factor, eosinophil chemotactic factor, and the enzyme phospholipase A. By migrating into connective tissues, basophils supplement the functions of mast cells as they have surface receptors for immunoglobulin E (IgE), and also secrete their granular components in response to certain antigens and allergens.

• Neutrophils are small, fast, and active scavengers protect the body against bacterial invasion and remove dead cells and debris from damaged tissues. Neutrophils are characterized by nuclei that are characteristically complex, with up to six lobes connected by thin nuclear extension, and their granules are lysosomes containing enzymes to digest engulfed material. The lifespan of neutrophils is an average of 6–9 hours in the bloodstream, and their numbers rise very quickly in an area of damaged or infected tissue. Mature neutrophils constitute 50%-70% of circulating leukocytes. The neutrophils are attracted in large numbers to any area of infection by chemicals called chemotaxins, released by damaged cells. Neutrophils are highly motile so that they can squeeze through the capillary walls in the affected area by the process called diapedesis. Neutrophils are the first leukocytes to reach the sites of infection where they actively pursue bacterial cells using chemotaxis and remove the invaders or their debris by phagocytosis.

Eosinophils are granulocytes with a bilobed nucleus that can be differentiated from other leukocytes based on the presence of abundant large, acidophilic specific granules typically staining pink or red.

Eosinophils are relatively less numerous than neutrophils, constituting only 1%-4% of total leukocytes.

Ultrastructurally the eosinophilic specific granules are seen to be oval in shape, with flattened crystalloid cores containing major basic proteins.

Eosinophils are particularly abundant in the connective tissue of the intestinal lining and at sites of chronic inflammation, such as lung tissues of asthma patients.

Eosinophils also modulate inflammatory responses by releasing chemokines, cytokines, and lipid mediators, with an important role in the inflammatory response triggered by allergies.

Some of the main functions of eosinophils are:

• Parasite defense: Eosinophils are involved in the defense against parasitic infections, especially helminths (worms). They attach to the surface of the parasites and release their granular contents, which contain cytotoxic and antiparasitic proteins. These proteins damage the parasite membrane and cause its death. Eosinophils also recruit other immune cells to the site of infection by secreting chemokines and cytokines.
• Allergic reactions: Eosinophils are activated by IgE antibodies that bind to allergens. They then release their granular contents, which contain histamine, leukotrienes, prostaglandins, and other inflammatory mediators. These substances cause vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion. These effects contribute to the symptoms of allergic diseases such as asthma, rhinitis, and dermatitis.
• Tissue remodeling: Eosinophils secrete growth factors and enzymes that promote tissue repair and remodeling after injury or inflammation. They also regulate angiogenesis (blood vessel formation) and fibrosis (scar tissue formation) by influencing the activity of fibroblasts and endothelial cells. However, excessive or chronic eosinophilic inflammation can lead to tissue damage and dysfunction.

Basophils are a type of white blood cell that play a role in protecting the body from infections and responding to allergens. They release histamines that help protect the body from certain substance exposures, such as pollen, dander, or mold. If the basophil count is unusually high, it may be a sign of infection or serious medical conditions like leukemia or autoimmune disease. Basophils are produced in the bone marrow and are released into the bloodstream . They are the least numerous kind of white blood cell in the blood, but are a key part of the immune response.

Structure of Basophils

Basophils are the smallest granulocytes with a diameter ranging between 10-14 µm. These polymorphonuclear cells have a polylobed nucleus and prominent, brightly metachromatic cytoplasmic granules. The nucleus contains condensed nuclear chromatin, but the nucleolus is absent. The cytoplasm contains organelles like mitochondria, vesicles, glycogen, and granules. The mature granules usually contain dense particles. Usually, human basophil cytoplasmic granules are round to angular, membrane-bound structures with sizes ranging up to 1.2 µm. The substructure of these granules contains dense particles in a less dense matrix occasional complex membrane. The cytoplasm has a complex vesicular system that is involved in basophil degranulation in the presence of an appropriate stimulus. The structure of basophils is similar to mast cells, and the differentiation can be made on the basis of glycogen content and the plasmalemma ridges.

Functions of Basophils

Basophils function to defend your body against:

• Allergens. Basophils have surface receptors for immunoglobulin E (IgE), which binds to specific antigens and triggers the release of histamine and other mediators of inflammation. Histamine enlarges your blood vessels to improve blood flow and heal the affected area. Histamine also opens pathways for other cells in your immune system to quickly target and respond to the allergen. You can identify when your basophil cells release histamines because you will experience physical symptoms of an allergic reaction like itchy skin, a runny nose and watery eyes.
• Bacterial, fungal and viral infections (pathogens). Basophils can recognize and bind to pathogens through their pattern recognition receptors (PRRs) and secrete cytokines and chemokines that recruit other immune cells to the site of infection.
• Blood clotting. Basophils also release an enzyme called heparin that prevents blood from clotting too quickly. The granules of basophils hold both histamine and heparin.
• Parasites. Basophils play an important role in fighting parasitic infections, especially helminths (worms). Basophils secrete interleukin 4 (IL-4) and interleukin 13 (IL-13), which promote the differentiation of helper T cells into type 2 helper T cells (Th2 cells). Th2 cells then stimulate B cells to produce IgE antibodies that coat the parasites and facilitate their destruction by eosinophils.

Neutrophils are the most abundant type of white blood cells in humans, making up 50%-70% of all leukocytes. They are part of the innate immune system and play a vital role in defending the body against bacterial infections and tissue damage .

Structure of Neutrophils

Neutrophils are round cells with a diameter of 12-15 μm that have a characteristic multi-lobed nucleus with 2-5 lobes connected by thin strands of chromatin . They are also called polymorphonuclear leukocytes because of their irregular nuclear shape. Their cytoplasm contains two types of granules: specific granules and azurophilic granules . Specific granules are smaller and more numerous, and they stain pink or purple with neutral dyes. They contain enzymes and proteins that help kill and digest bacteria, such as lysozyme, lactoferrin, defensins, and cathelicidins . Azurophilic granules are larger and fewer, and they stain blue with basic dyes. They are similar to lysosomes and contain enzymes that degrade ingested material, such as myeloperoxidase, elastase, cathepsin G, and proteinase 3 . Neutrophils are highly motile and can change their shape to squeeze through the capillary walls and migrate to the sites of infection or injury by following chemical signals called chemotaxins .

Functions of Neutrophils

Neutrophils are the first responders of inflammation and are recruited to the site of infection or injury within minutes . They perform two main functions: phagocytosis and degranulation . Phagocytosis is the process of engulfing and destroying bacteria and other microorganisms by forming a membrane-bound vesicle called a phagosome. The phagosome then fuses with the azurophilic granules to form a phagolysosome, where the bacteria are exposed to various enzymes and reactive oxygen species that kill them . Degranulation is the process of releasing the contents of the specific granules into the extracellular space or into the phagosome. The released substances have antimicrobial, cytotoxic, and pro-inflammatory effects that help eliminate the infection and activate other immune cells . Neutrophils can also release extracellular traps (NETs), which are web-like structures composed of DNA, histones, and granular proteins that trap and kill bacteria .

Neutrophils have a short lifespan of about 6-9 hours in the bloodstream and a few days in the tissues . They undergo programmed cell death (apoptosis) after completing their functions or when they become exhausted or damaged. Apoptotic neutrophils are then cleared by macrophages or other phagocytes to prevent tissue damage and inflammation .

Agranulocytes are a group of white blood cells that lack specific granules in their cytoplasm, which distinguishes them from granulocytes. Agranulocytes include the lymphocytes and monocytes, both of which are crucial for immunity and defense against antigens and pathogenic microorganisms. Agranulocytes make up about 35% of the total leukocytes in the blood.

a. Lymphocytes

Lymphocytes are round cells that contain a single, large round nucleus. There are two main classes of lymphocytic cells; the B cells that mature in the bone marrow, and the T cells that mature in the thymus gland. Lymphocytes are typically the smallest leukocytes and constitute approximately a third of these cells. Some lymphocytes circulate in the blood, but most cells remain in tissues, including lymphatic tissues such as lymph nodes and the spleen. Lymphocytes are formed from pluripotent stem cells in the red bone marrow and from precursors in lymphoid tissue. Lymphocytes, once activated, are involved in different forms of immune reactions.

• The activated B cells, also known as plasma cells, produce highly specific antibodies that bind to the agent that triggered the immune response.
• CD4 + (helper) T cells co-ordinate the immune response (they are what becomes defective in an HIV infection ).
• CD8 + (cytotoxic) T cells and natural killer cells (NK cells) are able to kill cells of the body that are infected by a virus.
• T cells have a unique `memory` system which allows them to remember past invaders and prevent disease when a similar invader is encountered again.

b. Monocytes

Monocytes are agranulocytes that are the largest of all white blood cells, some of which also act as precursor cells of macrophages, osteoclasts, microglia, and other cells of the mononuclear phagocyte system in connective tissue. Circulating monocytes have diameters of 12-15 μm, but macrophages are often somewhat larger. The monocyte nucleus is large and usually distinctly indented or C-shaped, and the cells have dense chromatin. The cytoplasm of the monocyte is basophilic and contains many small lysosomal azurophilic granules. Mitochondria and small areas of rough ER are present, along with a Golgi apparatus involved in the formation of lysosomes. Monocytes are crucial for inflammation as they produce interleukin 1 that enhances both the activation of B cells and phagocytosis. By migrating into connective tissues, monocytes differentiate into macrophages that can engulf and destroy foreign particles, dead cells, and debris. Monocytes also present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted.

Lymphocytes are a type of white blood cell that play a key role in the adaptive immune system, which is the part of the immune system that can recognize and remember specific antigens and mount a tailored response to them. Lymphocytes are derived from stem cells in the bone marrow and can be divided into two main classes: B lymphocytes (B cells) and T lymphocytes (T cells).

B cells are responsible for producing antibodies, which are proteins that bind to antigens and mark them for destruction by other immune cells or by complement proteins. B cells develop and mature in the bone marrow and then circulate in the blood and lymphatic system. When they encounter an antigen that matches their specific receptor, they become activated and differentiate into plasma cells or memory cells. Plasma cells secrete large amounts of antibodies into the blood and lymph, while memory cells persist for a long time and provide a faster and stronger response if the same antigen is encountered again.

T cells are involved in cell-mediated immunity, which is the defense against intracellular pathogens, such as viruses, bacteria, fungi, and parasites, as well as abnormal or cancerous cells. T cells develop in the bone marrow but mature in the thymus gland, where they undergo a process of selection to ensure that they do not react to self-antigens. T cells have receptors that recognize antigens presented by specialized cells called antigen-presenting cells (APCs), such as macrophages, dendritic cells, or B cells. There are several types of T cells with different functions:

• Helper T cells (Th cells) secrete cytokines that stimulate and regulate the activity of other immune cells, such as B cells, cytotoxic T cells, macrophages, and natural killer cells. Th cells can be further classified into subsets based on their cytokine profile and function, such as Th1, Th2, Th17, and Treg.
• Cytotoxic T cells (Tc cells or CTLs) directly kill infected or abnormal cells by releasing perforin and granzymes that induce apoptosis (programmed cell death). Tc cells also express a molecule called Fas ligand that binds to Fas on the target cell and triggers apoptosis.
• Regulatory T cells (Treg cells) suppress the immune response and prevent autoimmune reactions by producing anti-inflammatory cytokines and inhibiting the activation of other immune cells. Treg cells are essential for maintaining self-tolerance and immune homeostasis.

Lymphocytes constitute about 20% to 40% of the total white blood cell count in humans and have a lifespan ranging from a few days to several years. Lymphocytes can be found in the blood, lymphatic system, and various lymphoid tissues and organs, such as the spleen, tonsils, lymph nodes, thymus, appendix, Peyer`s patches, and mucosa-associated lymphoid tissue (MALT).

Monocytes are a type of white blood cell (leukocyte) that reside in your blood and tissues to find and destroy germs (viruses, bacteria, fungi and protozoa) and eliminate infected cells. Monocytes call on other white blood cells to help treat injury and prevent infection.

Structure of Monocytes

Monocytes are the largest cells in the peripheral blood, with the diameter ranging between 14-20 µm. The morphological features of the cells include an irregular cell shape, an oval or kidney-shaped nucleus, cytoplasmic vesicles, and a high nucleus to cytoplasm ratio (3:1). The nucleus is prominent and remains folded rather than multilobed. The cytoplasm, in turn, contains a large number of cytoplasmic granules, which are usually numerous towards the cell membrane. The nucleus contains a characteristic chromatin net with strands bridging tiny chromatin clumps. The surface of a monocyte contains ruffles and surface blebs which are of functional significance. Monocytes are motile and phagocytic; thus, the reduction of curvature of the cell by the formation of ruffles reduces repulsive forces with negative charge groups approach the cell. The cytoplasm contains mitochondria that are numerous, small in size, and elongated.

Function of Monocytes

Monocytes function as phagocytic cells and antigen-presenting cells in the peripheral blood to remove microorganisms, antigens, and dead or damaged cells. Different subsets of monocytes produce different cytokines that recruit additional cells and proteins to affected areas to generate an effective immune response.

Monocytes in the circulation are precursors of tissue macrophages that are actively phagocytic. Monocytes circulate in the blood for 1-3 days, and then migrate into body tissues, where they transform into macrophages. They will phagocytose dead cells and bacteria. Some monocytes can also transform into osteoclasts.

Monocytes can also differentiate into dendritic cells, which are specialized antigen-presenting cells that activate T cells and initiate adaptive immunity. Dendritic cells capture antigens from the tissues and migrate to lymph nodes where they present them to T cells.

Monocytes are essential for both the innate immune system and the adaptive immune system as these differentiate into macrophages and dendritic cells. Monocytes are one of the master cells of the immune system as these can perform a group of different functions performed by different immune cells. These can recognize danger signals or stimuli via their pattern recognition receptors, resulting in phagocytosis. These can also present antigens to other cells and secrete chemokine and cytokines. Monocytes can be defined as circulating blood cells that develop in the bone marrow from the common myeloid progenitor cells. However, monocytes are known for their developmental plasticity as these can differentiate into osteoclasts or other immune cells depending on the inflammatory response.

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