White Blood Corpuscles (Leukocytes) PDF

# White Blood Corpuscles (Leukocytes) ## Introduction - Why are they called White Blood Cells? After centrifugation, WBCs are found in the buffy coat, a thin white layer of cells between the sedimented RBCs and the plasma. **Image:** A test tube with different layers, the top is plasma (55% of...

# White Blood Corpuscles (Leukocytes) ## Introduction - Why are they called White Blood Cells? After centrifugation, WBCs are found in the buffy coat, a thin white layer of cells between the sedimented RBCs and the plasma. **Image:** A test tube with different layers, the top is plasma (55% of total blood), then a small layer of buffy coat (<1% of total blood), followed by erythrocytes (45% of total blood). - WBCs are nucleated cells that perform the defense functions of the body. - They destroy the invading microorganisms and destroy abnormal cells like cancer cells. ## Normal Values - **Total Leukocyte count** - Normal WBC count - **Adults:** 4000 - 11,000 / mm³ of blood - **At Birth:** 10,000 - 25,000 / mm³ of blood (count decreases after the 2nd week and reaches the normal adult value at 5 - 10 yrs.) ## Continued | CELL | ABSOLUTE COUNT (/cu.mm) | DIFFERENTIAL COUNT (%) | | --------------- | -------------------------- | ------------------------ | | Neutrophils | 3000 - 6000 | 50 - 70% | | Eosinophils | 150 - 300 | 1 - 4% | | Basophils | 10 - 100 | < 1% | | Lymphocytes | 1500 - 2700 | 20 - 40% | | Monocytes | 300 - 600 | 2 - 8% | ## WBC Count - The normal number of WBCs in the blood is 4,500 to 11,000 WBCs per microliter. - "Never Let Monkeys Eat Banana" - (60, 30, 6, 3, 1) - Neutrophils - 60% - Lymphocytes - 30% - Monocytes - 6% - Eosinophils - 3% - Basophils - 1% ## Variations In WBC Count - **Leukocytosis:** refers to an increase in WBC count above 11,000/mm³. - **Physiological causes:** - Newborn - Exercise - Mental stress - Pregnancy - After food intake - **Pathological Causes:** - Acute bacterial infections - Acute hemorrhage - Burns - Tuberculosis - **Leukopenia:** refers to WBC count below 4000 / mm³. - **Causes:** - Typhoid fever - Starvation - Viral and protozoal infections - Bone marrow depression **Fact:** Leukemia is a cancerous condition of blood in which the TLC is more than 50,000/cu.mm ASSOCIATED WITH THE PRESENCE OF IMMATURE WBCs in the peripheral smear. ## Classification - **Types of White Blood Cells:** - **Granulocytes:** - 1. Neutrophils - 2. Eosinophil - 3. Basophil - **Agranulocytes:** - 4. Lymphocyte - 5. Monocyte **Image:** A flowchart diagram with two branches labeled "Granulocytes" and "Agranulocytes". There are five boxes below those branches representing the 5 types of white blood cells. ## Neutrophils / Polymorphonuclear Leukocytes ### Morphology - **Size:** 10 - 14 µm diameter - **Nucleus:** - Young neutrophil - horseshoe shaped. - As the cells grow older, the nucleus becomes multi-lobed (2-6 lobes). - Mature neutrophil has a purple colored nucleus. **Image:** - An image of mature neutrophils with multi-lobed purple nuclei. - An image of a band cell (immature neutrophil) with a horseshoe-shaped nucleus. - An image of two neutrophils with a purple nucleus. ### Cytoplasm - Granular, slight bluish in color. ### Granules - Fine sand-like particles - Take both acidic and basic stains. Hence the name neutrophils (neutrophilic in nature). - Contains a variety of enzymes like glycosidases, sulphatases, phosphatases, nucleases, proteolytic enzymes etc. Hence can lyse any substance. - Also liberate histamine and peroxidase enzymes which help in killing the ingested bacteria. ### Lifespan and Fate - Neutrophils like all other leukocytes have four stages in their life: - Marrow Pool - Circulation pool: 8 - 10 hours - Marginated pool - Tissue pool: Either destroyed during phagocytosis or die due to senescence after 4 - 5 days. - A huge number of neutrophils are also eliminated daily, mainly into the intestine and some into the respiratory secretions. ### Functions - Neutrophils are actively phagocytic. - They are considered as the first line defense against acute bacterial infections - They contain a fever-producing substance called endogenous pyrogen which is an important mediator of febrile response to bacterial pyrogens. ### Neutrophil Phagocytosis - **Phagocytosis:** The process of ingestion and killing of microbes or a foreign substance by a phagocyte. - **Steps of Phagocytosis:** - Chemotaxis - Diapedesis - Adherence - Ingestion - Killing ### Chemotaxis - It is the process by which neutrophils are attracted towards bacteria at the site of inflammation. - It is mediated by chemotactic agents called chemotaxins. They are usually the microbial products or chemicals released from damaging tissues. These include Leukotriene B4, Complement proteins like C5a and C3. - Neutrophils change their shape and become amoeboid. - Leukopoiesis is stimulated and more neutrophils are produced. **Image:** A diagram of a leukocyte moving toward bacteria. ### Diapedesis - The process by which neutrophils pass through the capillary endothelial cells to reach the invader in the tissue is called diapedesis. - The activated neutrophils first marginate (margination and pavementing) and adhere tightly to endothelial lining with the help of L-selectins. - Then, by their amoeboid movement, they squeeze through the space between the endothelial cells (emigration and diapedesis). **Image:** A diagram of a leukocyte moving through the endothelial lining. ### Opsonization and Adherence - The process by which the bacteria are made tasty to the phagocyte is called Opsonization. - In this process, antigen is coated by opsonins. - Immunoglobulin G antibody and complement proteins are some examples. - The attachment of the membrane of phagocyte to the membrane of microbe is called adherence. **Image:** A diagram of a microbe being coated by opsonins. ### Ingestion (Endocytosis) - The membrane of phagocyte extends projections from both the sides to encroach on to the microbe. These extensions are called pseudopodia. - Pseudopodia finally surround the microbe and form a phagocytic vesicle. - The phagocytic vesicle fuses with the lysosome to form a phagolysosome. ### Killing or Degradation - The bactericidal mechanism can be broadly classified into: - Non-oxidative - Oxidative mechanisms - **Non-oxidative mechanism:** - Neutrophil granules contain a variety of anti-bacterial chemicals such as degradative enzymes, proteases, defensins, cationic proteins. - Lysozyme - hydrolyzes the cell wall, Lactoferrin - sequestrates iron - non-oxidative components. - Defensins - kill bacteria by disrupting the outer membrane and breaking single-strand DNA structure. - **Oxidative mechanisms:** - Following this, the cell membrane bound enzyme NADPH oxidase is activated. This causes a sharp uptake in O2. This is called respiratory burst. This leads to the formation of superoxide radical (O2) and Hydrogen peroxide (H2O2) as follows: - $NADPH + H+ + 2O2 → NADP+ + 2H+ + 2O2$ - $2O₂ + 2H+ → H_2O_2$ - $O2 + H_2O_2 → OH + OH + O_2$ - Hydroxyl radical is a very potent bactericidal agent. **Image:** A diagram of a neutrophil with different processes labeled. ### Variations - **Neutrophilia:** - Exercise - Cold - Stress - Acute pyogenic Bacterial infections - Burns - Hemorrhage - Drugs like epinephrine, glucocorticoids - **Neutropenia:** - Typhoid and Paratyphoid fever - Malaria - Aplastic anemia - Viral infections like measles, influenza - Drugs like chloramphenicol, pheytoin ## Eosinophils ### Morphology - **Size:** 10 - 14 µm diameter - **Nucleus:** Bilobed - spectacle shaped. Purple colored nucleus. - **Cytoplasm:** Acidophilic, light pink in color. - **Granules:** Coarse, stain bright red with eosin. **Image:** An image of a cell with bilobed purple nucleus and red granules. ### Granules - Major basic protein - Eosinophil catonic protein - Eosinophil derived peroxidase - Eosinophil derived neurotoxin - Cytokines ### Functions - Eosinophils participate in two important defense mechanisms of the body: - Against helminthic / parasitic infections - Against allergy - They attack parasites that are too large to be engulfed by phagocytosis. The granules release peroxidase which are toxic to larvae of parasites. - Eosinophils collect at the site of allergic reactions to release enzymes such as histaminase and thus limit the effects of inflammatory mediators. ### Variations - **Eosinophilia:** - Allergic conditions like bronchial asthma, allergic rhinitis, urticarial - Parasitic infections like filariasis, ascariasis - Tropical pulmonary eosinophilia - Drug reactions. - **Eosinopenia:** - Glucocorticoid therapy - Cushing's syndrome ## Basophils ### Morphology - **Size:** 10 - 14 µm diameter - **Nucleus:** Bilobed - S shaped. Purple colored nucleus. - **Cytoplasm:** Slight basophilic, blue in color. - **Granules:** Coarse, stains purple or blue with methylene blue. - Granules are plenty and overcrowd the nucleus. - **Granules contain:** histamine, heparin, serotonin and eosinophil chemotactic factor (ECF-A) of anaphylaxis. **Image:** An image of a basophil with an S-shaped nucleus and blue granules. ### Functions - Mild phagocytosis - Liberates histamine and ECF - A during an allergic reaction which leads to allergic manifestations. Mild urticaria to severe anaphylactic shock. - Liberates heparin which acts as an anti-coagulant. ### Variations - **Basophilia:** - Chickenpox - Smallpox - Tuberculosis - Influenza - Ulcerative colitis - Drug and food hypersensitivity - **Basopenia:** - Glucocorticoids - Hyperthyroidism - Cushing's syndrome ## Summary of Granulocytes - **Image:** A diagram of three different granulocytes. - Eosinophils – Kill parasitic worms. They also play a complex role in allergy and asthma. - Basophils – Release histamine and other mediators of inflammation - Neutrophils – Phagocytize bacteria. ## Lymphocytes ### Morphology - **Lymphocytes are of two types:** - **Large lymphocytes:** 10 - 14 µm diameter - **Small lymphocytes:** 7 - 10 µm diameter - **Nucleus:** - Single, big, Purple colored nucleus. - Round, oval or indented - Central in position and occupies the whole of the cell leaving marginal cytoplasm at one end of it or all around it. - Nuclear chromatin is coarse and lumpy. - **Cytoplasm:** Pale blue, scanty. **Image:** An image of a lymphocyte with a large purple nucleus surrounded by a small amount of pale blue cytoplasm. ### Functions - **Fuctionally, lymphocytes are divided into three categories:** - B cells - T cells - Natural killer cells (NK cells) - **B cells:** Secrete antibodies. Mediates humoral or antibody-mediated immunity. - **T cells:** Mediate cell-mediated immunity. - **NK cells:** Mediate natural and nonspecific immunity. ### Variations - **Lymphocytosis** - Children - Relative lymphocytosis (60%) - Chronic infections like TB - Lymphatic leukemia - Viral infections. - **Lymphocytopenia** - Hypoplastic bone marrow - AIDS ## Monocytes ### Morphology - **Size:** 10 – 18 µm diameter. Largest of WBCs. - **Nucleus:** Single, round or indented, eccentric, pale staining. - **Cytoplasm:** Pale blue in color, clear. - Sometimes contain fine dust-like granules - Azur granules. **Image:** An image of a monocyte with a large, indented purple nucleus and a clear pale blue cytoplasm. ### Functions - Monocyte is an active phagocyte. It is the second line of defense against infections. - It is an important Antigen Presenting Cell (APC) - Monocytes secrete various chemokines that carry out different physiological functions. - **Life span:** In circulation: 10 - 72 hrs. Then they enter tissues. Average lifespan is 3 months. In tissues, they become tissue macrophages. ### Variations - **Monocytosis:** - Acute monocytic leukemia - Hodgkin's disease - Polycythemia vera - Malaria - Kala-azar - **Monocytopenia:** - Aplastic anemia - Hairy cell leukemia - Septicemia ## Summary of Agranulocytes - **Image:** A diagram of four different agranulocytes. - Neutrophils – First to respond to bacteria or a virus. - Eosinophils – Known for their role in allergy symptoms. - Basophils – Known for their role in asthma. - Lymphocytes – Fight infections by producing antibodies. - Monocytes – Clean up dead cells.