[PHYSIO]LEC_006_WHITE-BLOOD-CELLS.pdf

(006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 - 3 types: o Poly...

(006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 - 3 types: o Polymorphonuclear cells OUTLINE ▪ with granular appearance ▪ called Granulocytes I. WHITE BLOOD CELLS ▪ polis – possess more nuclei A. Concentration of Different WBC ▪ Neutrophils, Eosinophils, Basophils o Monocytes and Lymphocytes in the blood o Do not have cytoplasmic granules B. Importance of WBC o Called Agranulocytes II. DIAPEDESIS - The granulocytes and monocytes protect the body against III. CHEMOTAXIS invading organisms by ingesting them (i.e., by phagocytosis) IV. PHAGOCYTOSIS or by releasing antimicrobial or inflammatory substances that have multiple effects that aid in destroying the offending A. Phases of Phagocytosis organism. V. MONOCYTE-MACROPHAGE CELL SYSTEM CONCENTRATIONS OF THE DIFFERENT WBC IN THE BLOOD - The adult human being has about 7,000 WBCs per microliter (RETICULOENDOTHELIAL SYSTEM) of blood VI. INFLAMMATION Polymorphonuclear Neutrophils 62.0% Polymorphonuclear Eosinophils 2.3% A. Inflammatory Process Polymorphonuclear Basophils 0.4% B. Characteristic of Inflammation Monocytes 5.3% C. Purpose of Inflammatory Lymphocytes 30.0% - The number of platelets, which are only cell fragments, in Response each microliter of blood is normally about 300,000. VII. TISSUE MACROPHAGE: FIRST LINE OF - Neutrophils DEFENSE o most abundant - it represents majority of the VIII. NEUTROPHIL INVASION OF THE WBCs. o Act as scavengers – surround and destroy INFLAMMED AREA: SECOND LINE OF bacteria and fungi DEFENSE - Lymphocytes o 2 cell types: IX. SECOND MACROPHAGE INVASION INTO ▪ B cell/B lymphocytes – produces THE INFLAMMED TISSUE: THIRD LINE OF antibodies to help the immune system mount up in to fight infection DEFENSE ▪ T cell/T lymphocytes – recognize and X. INCREASED PRODUCTION OF remove infection. GRANULOCYTES AND MONOCYTES BY THE - Monocytes o 2-8% of total WBC count; average: 5.3% BONE MARROW: FOURTH LINE OF o helps the body fight with chronic infection DEFENSE o precursors of macrophage and dendritic cells. - Eosinophils XI. FORMATION OF PUS o response to parasitic infections XII. EOSINOPHILS - Basophils o present in allergic reactions XIII. BASOPHILS XIV. LEUKOPENIA GENESIS OF WHITE BLOOD CELLS XV. LEUKEMIA - Two major lineages of WBCs are formed, the myelocytic and A. Types of Leukemia the lymphocytic lineages. Myelocytic lineage, beginning with the myeloblast and Lymphocytic lineage, beginning with the lymphoblast. - The different cells of the of the myelocyte series are: 1 – I. WHITE BLOOD CELLS myeloblast; 2 – promyelocyte; 3 – megakaryocyte; 4 – neutrophil myelocyte; 5 – young neutrophil metamyelocyte; - Also known as LEUKOCYTES 6 – “band” neutrophil metamyelocyte; 7 – - Are the mobile units of the body’s protective system polymorphonuclear neutrophil; 8 – eosinophil myelocyte; 9 - They are formed partially in the bone marrow (granulocytes eosinophil metamyelocyte; 10 – polymorphonuclear and monocytes and a few lymphocytes) and partially in the eosinophil; 11 – basophil myelocyte; 12 – lymph tissue (lymphocytes and plasma cells). After polymorphonuclear basophil; 13-16 – stages of monocyte formation, they are transported in the blood to different body formation parts. - Granulocytes and Monocytes are formed in the bone PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 marrow - WBCs – provide rapid and potent defense against infection - Lymphocytes are formed in different lymphogenous - In inflammation – neutrophils make the first wave of cells tissues—especially the lymph glands, spleen, thymus, that crosses the blood vessel wall and enter an inflamed tonsils, and various pockets of lymphoid tissue elsewhere in tissue. the body, such as in the bone marrow and in so-called - Monocyte enter inflamed tissue in the form of macrophages Peyer’s patches underneath the epithelium in the gut wall. - Later stages of inflammation – other leukocytes such as - The WBCs formed in the bone marrow are stored within the lymphocytes and eosinophils enter and participate in the marrow until they are needed in the circulatory system. inflammation process Then, when the need arises, various factors cause them to - Extravasation/Transmigration – process of leukocyte be released (these factors are discussed later). leaving the bloodstream entering the tissue. It occurs after - Normally, about three times as many WBCs are stored in diapedesis the marrow as circulate in the entire blood. This quantity represents about a 6-day supply of these cells. A. Neutrophils and monocytes can squeeze through the - The lymphocytes are mostly stored in the various lymphoid pores of the blood capillaries by DIAPEDESIS tissues, except for a small number that are temporarily being o even though a pore is much smaller than a cell, a transported in the blood. small portion of the cell slides through the pore at a time; the portion sliding through is momentarily constricted to the size of the pore. B. WBC’s move through tissue spaces by AMEBOID MOVEMENT o Both neutrophils and macrophages can move through the tissues by ameboid motion C. WBC’s are attracted to inflamed tissues by CHEMOTAXIS. - When a tissue becomes inflamed at least a dozen different products that can cause chemotaxis toward the inflamed area are formed. o bacterial or viral toxins o degenerative products of the inflamed tissues o reaction products of the “complement complex” activated in inflamed tissues o reaction products caused by plasma clotting in the inflamed area o other substances Figure 1. Genesis of white blood cells. Normal Body Flora - microorganisms that live on another living organism - As shown in the figure, megakaryocytes (cell 3) are also formed in the bone marrow. These megakaryocytes fragment in the bone marrow; the small fragments, known as platelets (or thrombocytes), then pass into the blood. They are very important in the initiation of blood clotting. IMPORTANCE OF WHITE BLOOD CELLS - Our bodies have a special system for combating the different infectious and toxic agents - This system is composed of blood leukocytes (WBC) and tissue cells derived from leukocytes - These cells work together in two ways to prevent diseases: - 1. By destroying invading bacteria or viruses by phagocytosis - 2. By forming Antibodies and Sensitized lymphocytes that may destroy or inactivate the invader Figure 2. Movement of WBCs towards the - The real value of WBCs is that most of them are specifically chemotaxis source transported to areas of serious infection and inflammation, thereby providing a rapid and potent defense against - chemotaxis depends on the concentration infectious agents. gradient of the chemotactic substance. The - Both Granulocytes and Monocytes have a special ability to concentration is greatest near the source, “SEEK OUT AND DESTROY” a foreign invader. which directs the unidirectional movement of PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 the WBCs. II. PHAGOCYTOSIS - The most important function of the neutrophils and macrophages is phagocytosis, “cellular ingestion of the offending agent” THREE SELECTIVE PROCEDURES 1. Most natural structures in the tissues have smooth surfaces, which resist phagocytosis. However, if the surface is rough, the likelihood of phagocytosis is increased. Figure 4. Macrophage 2. Most natural substances of the body have protective protein coats that repel the phagocytes. Conversely, most dead tissues and foreign particles have no protective coats, which III. PHASES OF PHAGOCYTOSIS makes them subject to phagocytosis. 3. The immune system of the body develops antibodies against infectious agents such as bacteria. The antibodies then adhere to the bacterial membranes and thereby make the bacteria especially susceptible to phagocytosis. To do this, the antibody molecule also combines with the C3 product of the complement cascade. The C3 molecules, in turn, attach to receptors on the phagocyte membrane, thus initiating phagocytosis. This process by which a pathogen is selected for phagocytosis and destruction is called opsonization. Figure 3. Phagocytosis - The neutrophils entering the tissues are already mature cells that can immediately begin phagocytosis. On approaching a particle to be phagocytized, the neutrophil first attaches itself to the particle and then projects pseudopodia in all directions around the particle. The pseudopodia meet one another on the opposite side and fuse. Figure 5. Phases of phagocytosis This action creates an enclosed chamber that contains the phagocytized particle. Then the chamber invaginates to the inside - Neutrophils and Macrophages Can Kill Bacteria. of the cytoplasmic cavity and breaks away from the outer cell - Much of the killing effect results from several powerful membrane to form a free-floating phagocytic vesicle (also called oxidizing agents formed by enzymes in the membrane of the a phagosome) inside the cytoplasm. phagosome or by a special organelle called the peroxisome. - A single neutrophil can usually phagocytize 3 to 20 bacteria o superoxide (O2− ) before the neutrophil becomes inactivated and dies. o hydrogen peroxide (H2O2) - Macrophages are the end-stage product of monocytes that enter o hydroxyl ions (OH−) the tissues from the blood. They are much more powerful o lysosomal enzymes, myeloperoxidase phagocytes than neutrophils, often capable of phagocytizing as - Myeloperoxidase - digestive enzyme that many as 100 bacteria. The precursors of macrophages are catalyzes reactions of hydrogen peroxide and monocytes. chloride ions producing Hypochlorite, a - Macrophages have the ability to engulf much larger particles, bactericidal agent even whole RBCs or, occasionally, malarial parasites, whereas - once phagocytized, most particles are neutrophils are not capable of phagocytizing particles much larger digested by intracellular Enzymes. than bacteria. - Phagocytes must be selective in the material that is - After digesting particles, macrophages can extrude the residual phagocytized, otherwise, even normal cells and structures of the products and often survive and function for many more months. body might also be ingested. - most natural structures in the tissues have smooth surface and this resists phagocytosis. If the surface is rough, phagocytosis PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 is increased - most natural substances of the body do not have protein coats that repel the phagocyte. Conversely, most dead tissues and V. INFLAMMATION foreign particles do not have this protective coat which make - When tissue injury occurs, whether caused by bacteria, trauma, themselves subject to phagocytosis. chemicals, heat, or any other phenomenon, multiple substances are - some bacteria have coats that are resistant to lysosomal released by the injured tissues and cause dramatic secondary digestion and also secrete substances that partially resist the changes in the surrounding uninjured tissues. killing effects of the neutrophils and macrophages. - This entire complex of tissue changes is called inflammation. - Lysosome Enzymes; Proteolytic enzymes-both in Macrophage - Inflammation is a natural response by our body when it feels as and Neutrophil, Lipase-only in Macrophages but not of though a threat has been made that may impact or harm the body’s neutrophil homeostasis or natural state. - Antibodies adhere to membranes of the bacteria making the bacteria susceptible to phagocytosis. INFLAMMATORY PROCESS - this process is in place to protect our body from threats such as different pathogens, toxins and injury IV. MONOCYTE-MACROPHAGE CELL SYSTEM (RETICULOENDOTHELIAL SYSTEM) - The total combination of monocytes, mobile macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes. - more commonly known as Reticuloendothelial system (RES) - located in tissues especially in tissues containing large number of particles, toxins or other amount of substances that must be destroyed Types of Macrophages Figure 7. Inflammatory process In the grand scheme of things, inflammation is good as it protects the body from foreign invaders and harmful substances. However, inflammation can also be harmful when it persists even when the threat of harmful substances has been removed from the body. We call it as Chronic inflammation. In injury, the resident tissue macrophage acts first. Next, mast cells and the circulating basophils releases a chemical called histamine. This histamine causes local vasodilation and increase Figure 6. Type of macrophages capillary permeability to cause recruitment of the leukocytes to the inflamed region. - Functions of R.E.S. Platelets cascades coagulation are now activated and releases o Removal of foreign objects and toxins blood protein and clotting elements from the blood and clotting o Formation of new red blood cells and white blood cells begins at the wound site. This will prevent pathogens from o Destruction of senescent RBCs spreading via blood. o Formation of plasma proteins o Formation of bile pigments Inflammatory response continues until the foreign materials are o Storage of iron eliminated and the wound is repaired. o Clearance of heparin via heparinase, etc. PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 “WALLING OFF” EFFECT OF INFLAMMATION CHARACTERISTICS OF INFLAMMATION - One of the first results of inflammation is to “wall off” the area of injury from the remaining tissues. - The tissue spaces and the lymphatics in the inflamed area are blocked by fibrinogen clots so that after a while, fluid barely flows through the spaces. This walling-off process delays the spread of bacteria or toxic products. This response helps to wall off infected area to further spread and allow the battle to focus at the inflammatory site. VI. TISSUE MACROPHAGES: FIRST LINE OF DEFENSE AGAINST INFECTION -Within minutes after inflammation begins, the macrophages already present in the tissues, whether histiocytes in the Figure 8. Characteristics of inflammation subcutaneous tissues, alveolar macrophages in the lungs, microglia in the brain, or others, immediately begin their phagocytic The inflammatory response that is initiated within hours of actions. infection or wounding is characterized by heat, redness, edema or swelling, tenderness or pain at the site of infection or injury. -Next, many of the previously sessile macrophages break Four (4) cardinal signs of inflammation: loose from their attachments and become mobile, forming the first - Rubor (Redness) line of defense against infection during the first hour or so. - Calor (Heat) - Palor (Pain) Tissue Macrophages in the Skin and Subcutaneous Tissues - Tumor (swelling) -When infection begins in a subcutaneous tissue and local - Loss of function (5th characteristics) inflammation ensues, local tissue macrophages can divide in situ and form still more macrophages. PURPOSE OF INFLAMMATORY RESPONSE Macrophages in the Lymph Nodes -If the particles are not destroyed locally in the tissues, they enter the 1. Allows the body to defend itself from invading lymph and flow to the lymph nodes located intermittently along the microorganisms. course of the lymph flow. The foreign particles are then trapped in - The increase in vascular diameter, and the these nodes in a meshwork of sinuses lined by tissue macrophages. activated endothelial cells, results in leukocytes being able Alveolar Macrophages in the Lungs to attach to the endothelium, and then migrate into the Large numbers of tissue macrophages are present as integral tissues where they can attack pathogens. components of the alveolar walls. They can phagocytize particles that become entrapped in the alveoli Macrophages (Kupffer Cells) in the Liver Sinusoids These cells form such an effective particulate filtration system that almost none of the bacteria from the gastrointestinal tract pass from the portal blood into the general systemic circulation. Macrophages of the Spleen and Bone Marrow In both these tissues, macrophages become entrapped by the reticular meshwork of the two organs and when foreign particles Figure 9. Inflammatory responses come in contact with these macrophages, they are phagocytized. 2. Induces local blood clotting, and this creates a physical barrier preventing the infection from spreading into the bloodstream. VII. NEUTROPHIL INVASION OF THE INFLAMED AREA: 3. Promotes the repair of injured tissues. SECOND LINE OF DEFENSE -Within the first hour or so after inflammation begins, large numbers of neutrophils begin to invade the inflamed area from the blood. Endothelial cells – lining of blood vessels Endothelial cell possesses different adhesion molecules: - P-selectin Figure 10. Repair of injured tissue - E-selectin - ICAM (intercellular adhesion molecules) PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 IX. INCREASED PRODUCTION OF GRANULOCYTES AND MONOCYTES BY THE BONE MARROW: FOURTH LINE OF DEFENSE This action results from stimulation of the granulocytic and monocytic progenitor cells of the marrow. However, it takes 3 to 4 days before newly formed granulocytes and monocytes reach the stage of leaving the bone marrow. If the stimulus from the inflamed tissue continues, the bone marrow can continue to produce these cells in tremendous quantities for months and even years, sometimes at a rate 20 to 50 times normal (specially in chronic inflammation). Control of the Macrophage Figure 11. Neutrophil invasion 1. They cause increased expression of adhesion molecules, such as selectins and intercellular adhesion molecule–1 (ICAM-1) on the surface of endothelial cells in the capillaries and venules. 2. They also cause the intercellular attachments between the endothelial cells of the capillaries and small venules to loosen, allowing openings large enough for neutrophils to crawl through directly from the blood into the tissue spaces by diapedesis. 3. They then cause chemotaxis of the neutrophils toward the injured tissues Neutrophilia- increase number of neutrophils to as high as 5x the normal. -within a few hours after the onset of acute, severe inflammation, the number of neutrophils in the blood sometimes increases fourfold to fivefold—from a normal of 4000 to 5000 to 15,000 to 25,000 neutrophils per microliter Figure 12. Control of macrophage -is caused by products of inflammation that enter the blood stream, are transported to the bone marrow, and their The cause of increased production of act on the stored neutrophils of the marrow to mobilize these granulocytes and monocytes by the bone marrow is mainly into the circulating blood. This makes even more neutrophils the three colony-stimulating factors, one of which, GM- available to the inflamed tissue area. CSF, G-CSF and M-CSF. Combination of TNF, IL-1, and colony-stimulating factors provides a powerful feedback mechanism that begins with tissue inflammation and proceeds to formation VIII. SECOND MACROPHAGE INVASION INTO THE of large numbers of defensive WBCs that help remove the INFLAMED TISSUE: THIRD LINE OF DEFENSE cause of the inflammation. - Along with the invasion of neutrophils, monocytes from the blood enter the inflamed tissue and enlarge to become macrophages. - After several days to several weeks, the macrophages finally come to dominate the phagocytic cells of the inflamed area because of greatly increased bone marrow production of new monocytes PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 o Releasing hydrolytic enzymes (modified lysosomes) X. FORMATION OF PUS o Releasing highly reactive forms of oxygen that are especially lethal to parasites (hydrogen peroxide) o Releasing highly larvicidal polypeptide called major basic protein Eosinophils also have a special propensity to collect in tissues in which allergic reactions Both mast cells and basophils release an eosinophil chemotactic factor that causes eosinophils to migrate toward the inflamed allergic tissue. Eosinophils are believed to detoxify some of the inflammation inducing substances released by the mast cells and basophils and probably also phagocytize and destroy allergen-antibody Figure 13. Formation of pus complexes, thus preventing excess spread of the local inflammatory process. When neutrophils and macrophages engulf large numbers of bacteria and necrotic tissue, essentially all the neutrophils and many, if not most, of the macrophages XII. BASOPHILS eventually die. After several days, a cavity is often excavated in the inflamed tissues. This cavity contains varying portions of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid (the mixture is commonly called pus). The whitish yellow or yellow brown or greenish color of the pus is because of the accumulation of dead neutrophils. Sometimes it appears green because neutrophil produces green antibacterial protein called myeloperoxidase). After the infection has been suppressed, the dead cells and necrotic tissue in the pus gradually autolyze over a period of days. the end products are eventually absorbed into the surrounding tissues and lymph until most of the evidence of tissue damage is gone. Figure 15. Basophils XI. EOSINOPHILS - Constitutes about 2% of the total blood leukocytes. Similar to mast cells however basophils are found in circulating blood while mast cells are found locally in tissues. They usually go together. Both mast cells & basophils liberate heparin (anticoagulant) into the blood which prevent coagulation Both release histamine, smaller amt. of bradykinin and serotonin (allergic reactions, pain, emotions) Both play an important role in allergic reactions IgE has propensity to attach to mast cells & basophils. The resulting attachment of antigen to antibody causes the mast cell or basophil to rupture and release large quantities of histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis and a number of lysosomal enzymes Figure 14. Eosinophils XII. LEUKOPENIA Weak phagocytes, exhibits chemotaxis Often produced in large numbers in people with parasitic infections and they migrate in large numbers into tissues Bone marrow produces very few WBCs diseases by parasites This condition leaves the body unprotected against many They are produced in large number in people with parasitic bacteria and other agents that might invade the tissues infection. They kill parasites by: PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 Any decrease in the number of WBC immediately allows invasion of the adjacent tissue by the bacteria. EFFECTS OF LEUKEMIA Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon. Bacteria from - The first effect of leukemia is metastatic growth of leukemic the ulcers rapidly invade surrounding tissues and the cells in abnormal areas of the body blood. Without treatment, death often ensues in less than a week after acute total leukopenia begins. - Leukemic cells from the bone marrow may invade the surrounding bone, causing pain and a tendency for bones Irradiation of the body by x-rays or gamma rays, or exposure for fracture easily. to drugs and chemicals that contain benzene or anthracene nuclei, is likely to cause aplasia of the bone - There’s development of infection, severe anemia, and marrow. bleeding tendency caused by thrombocytopenia. These effects result mainly from displacement of the normal bone Some drugs such as Chloramphenicol (an antibiotic), marrow and lymphoid cells by the nonfunctional leukemic Thiouracil (used to treat thyrotoxicosis) and even various cells. barbiturate hypnotics on rare occasions cause Leukopenia. - Another important effect of leukemia on the body is excessive use of metabolic substrates by the growing cancerous cells XIV. LEUKEMIA - The leukemic tissues reproduce new cells so rapidly that - High WBC but abnormal WBC tremendous demands are on the body reserves for foodstuff, amino acids, and vitamins. - Consequently, the energy of the patient is greatly depleted, and excessive utilization of amino acids by the leukemic cells causes especially rapid deterioration of the normal protein tissues of the body. Thus, while the leukemic tissues grow, other tissues become debilitated. After metabolic starvation has continued long enough, this factor alone is sufficient to cause death. Figure 16. Leukemia ✓ a disease characterized by greatly increased numbers of WBCs in the circulating blood TEST YOUR KNOWLEDGE ✓ Uncontrolled production of WBCs can be caused by cancerous mutation of a myelogenous or lymphogenous cell precipitated by environmental factors. 1. Type of lymphocyte that produces antibodies a. T cells TWO TYPES OF LEUKEMIA: b. B cells c. Plasma cells 1.LYMPHOCYTIC LEUKEMIA (ACUTE LL or CHRONIC LL) d. Natural killer cells 2. MYELOGENOUS LEUKEMIA (AML or CML) ACUTE- cut off is 6 months 2. Leukocyte that participate in allergic process CHRONIC- more than 6 months of occurrence a. Neutrophil b. Eosinophil LYMPHOCYTIC LEUKEMIA c. Basophil -caused by cancerous production of lymphoid cell, beginning in a d. Mast cells lymph nodes or other lymphocytic tissue and spreading to other areas of the body. 3. Specific macrophage found in liver - affects the lymphoid cells/lymphocytes a. Kupfler cells b. Histocytes MYELOGENOUS LEUKEMIA c. Microglia d. Mesangial cells -begins by cancerous production of young and myelogenous cells in the bone marrow and then spreads throughout the body so that WBCs 4. This cancer cells affects the lymphatic tissues for more than are produced in many extramedullary tissues especially in the lymph two years nodes, spleen and liver. a. Acute Myelogenous Leukemia -affects the myeloid cells that give rise to WBC and platelets b. Chronic Myelogenous Leukemia PREPARED AND EDITED BY: TRANS GROUP 6  (006) WHITE BLOOD CELLS DR. MA EILEEN O PASCUA| 10/28/2020 c. Acute Lymphocytic Leukemia d. Chronic Lymphocytic Leukemia 5. Specific macrophage found in the gut a. Microglia b. Intestinal macrophage c. Histocytes d. Alveolar macrophages Answer Key: 1. B, 2. C, 3. A, 4. D, 5. B REFERENCES Hall, J. E., & Guyton, A. C. (2011). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier. PREPARED AND EDITED BY: TRANS GROUP 6