White Blood Cells Physiology Notes

White Blood Cells Introduction

White blood cells (WBCs) or leukocytes are the colorless and nucleated formed elements of blood (leuko = white or colorless). Compared to RBCs, the WBCs are larger in size and lesser in number.

Yet functionally, these cells are important like RBCs. Leukocytes play a very important role in defense mechanism of body and protect the body from invading organisms by acting like soldiers. WBCs differ from RBCs in many aspects, viz.

1. Larger in size
2. Irregular in shape
3. Nucleated
4. Many types
5. Granules are present in some type of WBCs
6. Life span is shorter

Read And Learn More: Medical Physiology Notes

Classification Of White Blood Cells

Some of the WBCs have granules in the cytoplasm. Based on the presence or absence of granules in the cytoplasm, the leukocytes are classified into 2 groups:

1. Granulocytes – with granules
   1. Neutrophils
   2. Eosinophils
   3. Basophils,
2. Agranulocytes – without granules
   1. Monocytes
   2. Lymphocytes.

Morphology Of White Blood Cells

1. Neutrophils:
   • Neutrophils which are also known as polymorphs have fine or small granules in the cytoplasm. The granules take acidic and basic stains.
   • When stained with Leishman’s stain (which contains acidic eosin and basic methylene blue) the granules appear violet in color.
   • The nucleus is multilobed. The number of lobes in the nucleus depends upon the age of cell.
   • In younger cells, the nucleus is not lobed. And in older neutrophils, the nucleus has 2-5 lobes. The diameter of cell is 10-12 μ. The neutrophils are ameboid in nature.
2. Eosinophils: Eosinophils have coarse (larger) granules in the cytoplasm, which stain pink or red with eosin. The nucleus is bilobed and spectacle shaped. The diameter of the cell varies between 10 and 14 μ.
3. Basophils: Basophils also have coarse granules in the cytoplasm. The granules stain purple blue with methylene blue. The nucleus is bilobed. The diameter of the cell is 8-10 μ.
4. Monocytes: Monocytes are the largest leukocytes with diameter of 14-18 μ. The cytoplasm is clear without granules. The nucleus is round, oval, horseshoe-shaped, bean-shaped, or kidney-shaped. The nucleus is placed either in the center of the cell or pushed to one side and a large amount of cytoplasm is seen.
5. Lymphocytes: Like monocytes, the lymphocytes also do not have granules in the cytoplasm. The nucleus is oval, bean-shaped, or kidney-shaped. The nucleus occupies the whole of the cytoplasm. A rim of cytoplasm may or may not be seen.

Depending upon the size, the lymphocytes are divided into two groups:

1. Large lymphocytes: The younger cells with a diameter of 10-12 μ
2. Small lymphocytes: The older cells with a diameter of 7-10 μ.

Depending upon the function, the lymphocytes are divided into two types:

1. T lymphocytes: Concerned with cellular immunity
2. B lymphocytes: Concerned with humoral immunity.

Normal White Blood Cell Count

1. Total WBC count (TC): 4,000-11,000 /cu. mm of blood
2. Differential WBC count (DC): Given in the Table.

Variations In White Blood Cell Count

1. Leukocytosis: Leukocytosis is the increase in WBC count. Leukocytesis occurs in both physiological and pathological conditions.
2. Leukopenia: Leukopenia is the decrease in leukocyte count. The term leukopenia is generally used for pathological conditions only.
3. Granulocytosis: It is the abnormal increase in the number of granulocytes.
4. Granulocytopenia: Granulocytopenia is the abnormal reduction in the number of granulocytes.
5. Agranulocytosis: Agranulocytosis is an acute pathological condition characterized by an absolute lack of granulocytes.

Physiological Variations

1. Age: The WBC count is about 20,000 per cu mm in infants and about 10,000-15,000 per cu mm of blood in children. In adults it ranges between 4000 and 11000 per cu mm of blood
2. Sex: Slightly more in males than in females
3. Diurnal variation: Minimum in early morning and maximum in the afternoon
4. Exercise: Increases slightly
5. Sleep: Decreases
6. Emotional conditions like anxiety: Increases
7. Pregnancy: Increases
8. Menstruation: Increases
9. Parturition: Increases

Pathological Variations: All types of leukocytes do not share equally in the increase or decrease in the total leukocyte count. In general, the neutrophils and lymphocytes vary in opposite directions.

1. Leukocytosis: Leukocytosis is the increase in total leukocyte count occurs in conditions such as:
   1. Infections
   2. Allergy
   3. Common cold
   4. Tuberculosis
   5. Glandular fever.
      • However, differential leukocyte count increases in specific diseases.
2. Neutrophilia: Neutrophilia or neutrophilic leukocytosis is the increase in neutrophil count. It occurs in the following conditions:
   1. Acute infections
   2. Metabolic disorders
   3. Injection of foreign proteins
   4. Injection of vaccines
   5. Poisoning by chemicals and drugs like lead, mercury, camphor, benzene derivatives, etc.
   6. Poisoning by insect venom
   7. After acute hemorrhage.
3. Eosinophilia: Eosinophilia is the increase in eosinophil count and it occurs in:
   1. Asthma and other allergic conditions
   2. Blood parasitism (malaria, filariasis)
   3. Intestinal parasitism
   4. Scarlet fever.
4. Basophilia: Basophilia is the increase in basophil count and it occurs in:
   1. Smallpox
   2. Chickenpox
   3. Polycythemia vera.
5. Monocytosis: Monocytosis is the increase in monocyte count and it occurs in:
   1. Tuberculosis
   2. Syphilis
   3. Malaria
   4. Kala-azar
   5. Glandular fever.
6. Lymphocytosis: Luponosis is the increase in lymphocyte count and ontraria
   1. Infectious hepatitis
   2. Malnutrition
   3. Rickets
   4. Syphilis
   5. Thyrotoxicosis
   6. Tuberculosis.
7. Leukemia: Leukemia is a condition, which is characterized by an abnormal and uncontrolled increase in leukocyte count more than 1,000,000/ cu mm. It is also called blood cancer.
8. Leukopenia: Leukopenia is the decrease in the total WBC count. It occurs in the following pathological conditions:
   1. Anaphylactic shock
   2. Cirrhosis of liver
   3. Disorders of spleen
   4. Pernicious anemia
   5. Typhoid and paratyphoid
   6. Viral infections.
      • However, differential leukocyte count decreases in specific diseases.
9. Neutropenia: Neutropenia is the decrease in neutrophil count. It occurs in:
   1. Bone marrow disorders
   2. Typhoid
   3. Vitamin deficiencies
   4. Autoimmune diseases.
10. Eosinopenia: the decrease in eosinophil count is called eosinopenia. It occurs in:
    1. Cushing’s syndrome
    2. Bacterial infections
    3. Stress
    4. Prolonged administration of drugs such as steroids, Neutrophils, monocytes, and lymphocytes show amebic ACTH and epinephrine.
11. Basopenia: Basopenia or basophilic leucopenia is the decrease in basophil count. It occurs in:
    1. Urticaria (skin disorder)
    2. Stress
    3. Prolonged exposure to chemotherapy or radiation therapy.
12. Monocytopenia: Monocytopenia is the decrease in monocyte count. It occurs in:
    1. Prolonged use of prednisone (immunosuppressant steroid)
    2. AIDS
    3. Chronic lymphoid leukemia.
13. Lymphocytopenia: Lymphocytopenia is the decrease in lymphocytes. It Neutrophils play an important role in the defense occurs in:
    1. AIDS
    2. Hodgkin’s disease (cancer of the lymphatic system) invading microorganisms. The neutrophils are the free
    3. Malnutrition
    4. Radiation therapy
    5. Steroid administration.

Lifespan Of White Blood Cells

Lifespan of WBCs is not constant. It depends upon the demand in the body and their function. The lifespan of these cells may be as short as half a day or it may be as long as 3-6 months. However, the normal lifespan of WBCs is as follows:

Neutrophils Eosinophils: 2-5 days

Eosinopenia: 7 – 12 days

Basophils: 12 15 days

Monocytes: 2-5 days

Lymphocytes: 1/2 -1 day

Properties Of White Blood Cells

1. Diapedesis: Diapedesis is the process by which the leukocytes squeeze through the narrow blood vessels.
2. Ameboid Movement: Neutrophils, monocytes, and lymphocytes show amebic movement characterized by protrusion of the cytoplasm and change in shape.
3. Chemotaxis: Chemotaxis is the attraction of WBCs towards the injured tissues by the chemical substances released at the site of injury.
4. Phagocytosis: Neutrophils and monocytes engulf the foreign bodies by means of phagocytosis.

Functions Of White Blood Cells

Generally, WBCs play an important role in defense mechanisms. These cells protect the body from invading organisms or foreign bodies either by destroying or inactivating them. However, in defense mechanisms, each type of WBCs acts in a different way.

Neutrophils: neutrophils play an important role in the defense mechanism of the body. Along with monocytes, neutrophils provide the first line of defense against the invading microorganisms. The neutrophils are the free cells in the body and wander freely through the tissue and practically no part of the body is spared by these leukocytes.

• Substances Present in Granules and Cytoplasm
  • The granules of neutrophils contain enzymes like proteases, myeloperoxidases, elastases and metalloproteinases. These enzymes destroy the microorganisms.
  • The granules also contain antibody-like substances called defensins. Defensins are antimicrobial peptides, which are active against bacteria and fungi.
  • The membrane of neutrophils contains an enzyme called NADPH oxidase (dihydro nicotinamide adenine dinucleotide phosphate oxidase). It is activated by the toxic metabolites released from infected tissues.
  • The activated NADPH oxidase is responsible for bactericidal action of neutrophils.
  • All these substances present in the granules and cell membrane make the neutrophil a powerful and effective killer machine.
  • Neutrophils also secrete platelet-activating factor (PAF) which is a cytokine. It accelerates the aggregation of platelets during injury to the blood vessel resulting in the prevention of excess loss of blood.
• Mechanism of Action of Neutrophils
  • Neutrophils are released in large number from the blood at the time of infection by the microorganisms. At the same time, new neutrophils are produced from the progenitor cells. All the neutrophils move by diapedesis and are attracted toward the site of infection by means of chemotaxis.
  • The chemotaxis occurs due to the attraction by some chemical substances called chemoattractants, which are released from the infected area.
  • After reaching the area, the neutrophils surround the area and get adhered to the infected tissues. The chemoattractants increase the adhesive nature of neutrophils so that all the neutrophils become sticky and get attached firmly to the infected area.
  • Each neutrophil can hold about 15-20 microorganisms at a time. Now, the neutrophils start destroying the invaders. First, these cells engulf the bacteria and then destroy them by means of phagocytosis.
• Respiratory Burst:
  • Respiratory burst is a rapid increase in oxygen consump- tion during the process of phagocytosis by neutrophils and other phagocytic cells.
  • Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for this phenomenon. During respiratory bursts, the free radical O₂^– is formed. Two O₂^– combine with two H⁺ to form H₂O₂ (hydrogen peroxide). Both O₂^– and H₂O₂ are oxidants having potent bactericidal action.
• Pus and Pus Cells:
  • Pus is the whitish-yellow fluid formed in the infected tissue by the dead WBCS, bacteria or foreign bodies, and cellular debris. It consists of white blood cells, bacteria or other foreign bodies and cellular debris. The dead WBCs are called the pus cells.
  • During the battle against the bacteria, many WBCs are killed by the toxins released by the bacteria. The dead cells are collected in the center of the infected area. The dead cells together with plasma leaked from the blood vessel, and liquefied tissue cells and RBCs escaped from damaged blood vessel (capillaries) constitute the pus.

Eosinophils

• The eosinophils play an important role in the defense mechanism of the body against the parasites. During parasitic infections, there is production of a large number of eosinophils which move towards the tissues affected by parasites.
• The eosinophil count increases also during allergic diseases like asthma.
• The eosinophils are responsible for the detoxification, disintegration, and removal of foreign proteins.
• Mechanism Of Action Of Eosinophils
  • The ensinophils are neither markedly motile nor phagocytes like the neutrophils. Some of the parasites are larger in size. Still, eosinophils attack them by some special type of cytotoxic substances present in their granules.
  • When released over the invading parasites from the granules, these substances become lethal and destroy the parasites. The lethal substances present In the granules of eosinophils and released at the time of exposure to parasites or foreign proteins are:
    1. Eosinophil peroxidase: This enzyme is capable of destroying helminths (worms), bacteria and tumor cells.
    2. Major basic protein (MBP): It is very active against helminths. It destroys the parasites by causing distension (ballooning) and detachment of the tegu- mental sheath (skin like covering) of these organisms.
    3. Eosinophil cationic protein (ECP): This substance is the major destroyer of helminths and it is about 10 times more toxic than MBP. It destroys the parasites by means of complete disintegration. It is also a neurotoxin.
    4. Eosinophil-derived neurotoxin: It destroys the nerve fibers, particularly the myelinated nerve fibers.
    5. Cytokines: Cytokines such as interleukin-4 and interleukin-5 accelerate inflammatory responses and kill the invading organisms.

Basophils

• The basophils play an important role in the healing process. So their number increases during healing process.
• Basophils also play an important role in allergy or acute hypersensitivity reactions (allergy). This is because of the presence of receptors for the IgE basophil membrane.

1. Mechanism of Action of Basophils: The functions of basophils are executed by the release of some important substances from their granules such as:
   1. Heparin: Heparin is essential to prevent the intra-vascular blood clotting
   2. Histamine, slow-reacting substances of anaphylaxis, bradykinin, and serotonin: These substances produce acute hypersensitivity reactions by causing vascular and tissue responses.
   3. Proteases and myeloperoxidase: These enzymes exaggerate the inflammatory responses.
   4. Cytokine: Cytokine such as interleukin-4 accelerates inflammatory responses and kill the invading organisms.
2. Mast Cell: Mast cell is a large tissue cell resembling the basophil. Generally, mast cells are found along with the blood vessels and are prominently seen in the areas such as skin, mucosa of the lungs and digestive tract, mouth, conjunctiva, and nose. These cells usually do not enter the bloodstream.
   1. Origin: Mast cells are developed in the bone marrow, but their precursor cells are different. After differentiation, the immature mast cells enter the tissues. The maturation of mast cells takes place only after entering the tissue.
   2. Functions: The mast cell plays an important role in producing the hypersensitivity reactions like allergy and anaphylaxis. When activated the mast cell immediately releases various chemical mediators from its granules into the interstitium. Two types of substances are secreted by mast cells:
      1. Preformed mediators: These substances are already formed and stored in secretory granules. These substances are histamine, heparin, serotonin, hydrolytic enzymes, proteoglycans, and chondroitin sulphates
      2. Newly generated mediators: These substances are absent in the mast cell during resting conditions and are produced only during activation. These substances are arachidonic acid derivatives such as leukotriene C (LTC) and prostaglandin and cytokines.

Monocytes:

• Monocytes are the largest cells among the leukocytes. Like neutrophils, monocytes also are motile and phagocytic in nature. These cells wander freely through all tissue of the body.
• Monocytes play an important role in the defense of the body. Along with neutrophils, these leukocytes provide the first line of defense. Monocytes secrete:

1. Interleukin-1 (IL-1)
2. Colony stimulating factor (M-CSF)
3. Platelet-activating factor (PAF).

• Monocytes are the precursors of the tissue macrophages. The matured monocytes stay in the blood only for a few hours.
• Afterward, these cells enter the tissues from the blood and become tissue macrophages. Examples of tissue macrophages are Kupffer cells in the liver, alveolar macrophages in the lungs, and macrophages in the spleen.

Lymphocytes:

• The lymphocytes play an important role in immunity. Functionally, the lymphocytes are classified into two categories namely T lymphocytes and B lymphocytes.
• T lymphocytes are responsible for the development of cellular immunity and B lymphocytes are responsible for the development of humoral immunity.

Leukopoiesis

Leukopoiesis is the development and maturation of leukocytes.

Stem Cells:The committed pluripotent stem cell gives rise to leukocytes through various stages.

Factors Necessary For Leukopoiesis: Leukopoiesis is influenced by hemopoietic growth factors and colony-stimulating factors.

Colony Stimulating Factors

• The colony-stimulating factors (CSF) are proteins that cause the formation of colony-forming blastocytes.
• Colony stimulating factors are of three types:

1. Granulocyte CSF (G-CSF) secreted by monocytes and endothelial cells
2. Granulocyte-Monocyte CSF (GM-CSF) secreted by monocytes, endothelial cells, and T lymphocytes
3. Monocyte CSF (M-CSF) secreted by monocytes and endothelial cells.