White Blood Cells In The Body (2024) PDF

COURSE OUTLINE CONCENTRATIONS OF THE DIFFERENT WHITE BLOOD CELLS IN THE BODY I. WHITE BLOOD CELLS A. Concentrations Of The Different Wbc In The adult human body has about 7000 WBCs...

COURSE OUTLINE CONCENTRATIONS OF THE DIFFERENT WHITE BLOOD CELLS IN THE BODY I. WHITE BLOOD CELLS A. Concentrations Of The Different Wbc In The adult human body has about 7000 WBCs The Blood per microliter of blood B. Genesis Of White Blood Cells ○ Polymorphonuclear neutrophils —-- 62.0% C. Importance Of White Blood Cells ○ Polymorphonuclear eosinophils —---2.3% I. Diapedesis ○ Polymorphonuclear basophils —------0.4% Ii. Ameboid Movement ○ Monocytes —-------------------------------5.3% Iii. Chemotaxis ○ Lymphocytes —---------------------------30.0% II. PHAGOCYTOSIS A. Stages Of Phagocytosis Normal WBC in the body: 4500 to 11000 WBCs III. MONOCYTE-MACROPHAGE CELL SYSTEM per microliter of blood (RETICULOENDOTHELIAL SYSTEM) Neutrophils represent majority of the WBCs in IV. INFLAMMATION the body - they are the scavengers, kills A. Inflammation Process bacteria, fungi B. Characteristics Of Inflammation Lymphocytes for viruses, they possess 2 main C. Purpose Of Inflammation cell types, the B-cell Lymphocyte and T-cell V. THE “WALLING-OFF” EFFECT Lymphocyte. VI. FIRST LINE OF DEFENSE: TISSUE ○ T-cell Lymphocytes responsible for MACROPHAGE production the bodies different antibodies VII. SECOND LINE OF INVASION: NEUTROPHIL ○ B-cell Lymphocytes responsible for the INVASION OF THE INFLAMED AREA recognition and removal of the infection VIII. THIRD LINE OF DEFENSE: SECOND causing cells. MACROPHAGE INVASION INTO THE Monocytes (2-8%) present during chronic INFLAMED TISSUE inflammation, precursor of macrophage and IX. FOURTH LINE OF DEFENSE: INCREASED dendritic cells. PRODUCTION OF GRANULOCYTES AND Eosinophils, responsible for responding to MONOCYTES BY THE BONE MARROW infections caused by parasites. X. FORMATION OF PUS Basophils (least number), typically present XI. EOSINOPHILS during allergic reaction. XII. BASOPHILS XIII. LEUKOPENIA XIV. LEUKEMIA A. Two Types of Leukemia B. Effect of Leukemia I.WHITE BLOOD CELLS Resistance of the body to Infection Leukocytes, Granulocytes, the Monocyte-Macrophage System and Inflammation LEUKOCYTES (White Blood Cells) Figure 1. Different types of white blood cells. Are the mobile units of the body’s protective system Formation of lymphocytes occur in different Also called LEUKOCYTES lymphogenous tissues. Mobile units of the human body’s protective The WBCs formed in the bone marrow are system stored within the marrow until they are needed Types of WBC: Granulocytes and in the circulatory system then, if needed, Agranulocytes: various factors cause them to be released. Granulocytes: it has granules inside: Eosinophils, Basophils and Neutrophils Agranulocytes: it does not have any cytoplasmic granules: Lymphocytes and Monocytes. Formed partly in the bone marrow—where granulocytes, monocytes, and some lymphocytes are produced—and partly in the lymph tissue, where lymphocytes and plasma cells are generated. Once formed, these cells are carried through the bloodstream to various parts of the body. BATCH 2028 1B 1 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 GENESIS OF THE WHITE BLOOD CELLS septicemia, pneumonia, meningitis, urosepsis, typhoid, and other infections. Once inflammation happens, the neutrophil makes the first wave of cells that crosses the cell. Next is, the monocyte also crosses the blood vessels and differentiates that into macrophage. Both granulocytes and monocytes have a special ability to “seek and destroy” a foreign invader. WBCs work together in ways to prevent infection. First destroys bacteria by means of phagocytosis. Aside from this, WBC also produces antibodies and synthesize lymphocytes that may destroy or inactivate the invader. Figure 2. Genesis of white blood cells 1. Phagocytosis is through neutrophils and macrophages. Macrophage is from In the image above, the 2 lineages of WBC are monocytes. Monocytes are from the shown which are the Myelocytic and circulating blood cells. Once it gets outside Lymphocytic. the blood vessels and go to the site of Myelocytic starts as the myeloblast (original), infection in the tissues, it is then called then the promyelocyte until it becomes the macrophages. mature neutrophils, eosinophil, basophils 2. Lymphocytes responsible for the It is also in the myelocytic series where production of antibodies, particularly, the monocytes are produced. B-cell Lymphocytes. Produced and stored in the bone marrow until it is needed in the circulation. Once infection has begun, the neutrophils are the Lymphocytic series, leukocytes only. Starts first to emerge from the blood vessel to the site of with lymphoblast. Until it becomes the infection. Monocytes will follow and become lymphocytes and plasma cells. macrophages. Neutrophils and Macrophages are It is stored in the lymphoid tissues able to do phagocytosis (cell eating). Granulocytes and monocytes are produced in the bone marrow, while lymphocytes and In later stages of infection, eosinophils and plasma cells are generated in various lymphoid lymphocytes will follow. tissues. 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: ○ By destroying invading bacteria or viruses by phagocytosis. ○ By forming antibodies and sensitized lymphocytes that destroy or inactivate the invader Figure 3. Diapedesis The real value of WBCs in that most of them are specifically transported to area of serious Neutrophils and monocytes can squeeze infection and inflammation, thereby providing a through the pores of the blood capillaries by rapid and potent defense against infectious DIAPEDESIS. agents We are constantly exposed to bacteria, viruses, Diapedesis is the process of rolling and fungi, and parasites, which are normally squeezing of leukocytes between cells and present in varying amounts on our skin, in the capillary walls so that it can exit out of the mouth, respiratory passages, intestinal lining, blood vessel. urinary tract, and the membranes of the eyes. Transmigration or Extravasation is the These are referred to as normal body flora. process of the leukocyte leaving the However, when these organisms invade deeper bloodstream and entering the tissues of the tissues, they can cause abnormal physiological area of infection/inflammation. functions or even severe conditions such as BATCH 2028 1A 2 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 Can be seen in different organs. They sometimes swell, five times its size, 60-80 micrometer. PHASES OF PHAGOCYTOSIS Figure 4. Movement of neutrophils by diapedesis through capillary pores and by chemotaxis toward an area of tissue damage WBC’s are Attracted to Inflamed Tissue Areas Figure 6. Parts of the macrophage. by CHEMOTAXIS. When a tissue becomes inflamed, different Once it gets inside the cells, the ingestion of products causes chemotaxis toward the the phagocyte will form the phagosome or inflamed area are formed phagocytic vesicle. ○ Bacterial or viral toxins The cell has lysosome, which is the suicidal ○ Degenerative products of the inflamed bomb of the cell, it contains hydrolytic enzyme tissues capable of digesting and crushing the ○ Reaction products of the “complement pathogens. complex” activated in inflamed tissues The partially digested microbes are then ○ Reaction products caused by plasma discharged as inactive. clotting in the inflamed area Phagocytes need to be selective, if not, even ○ Other substances normal cells will be phagocytosed. Chemotactic substance: CHEMOKINE Whether phagocytosis will occur depending on this 3 selective procedures: II. PHAGOCYTOSIS 1. Most natural structures in the tissues have The most important function of neutrophils and smooth surfaces, which resist phagocytosis. macrophages is PHAGOCYTOSIS, “cellular However, if the surface is rough, the ingestion of the offending agent likelihood of phagocytosis is increased. A single neutrophil can usually phagocytize 2. Most natural substances of the body have 3-20 bacteria before the neutrophil becomes protective protein coats that repel the inactivated and dies phagocytes. Conversely, most dead tissues and foreign particles have no protective coats, which makes them subject to phagocytosis. 3. Immune system of the body develops antibodies against infectious agents such as bacteria. The antibodies adhere to the bacterial membranes and thereby make the Figure 5. Stages of Phagocytosis bacteria especially susceptible to Approaching the particles, WBC will go to the phagocytosis. To do this, the antibody particle, upon approaching, the WBC will create molecule also combines with the C3 product a pseudopodia until both ends of the WBC are of the complement cascade; the C3 fused, creating an enclosed chamber. molecules, in turn, attach to receptors on the phagocyte membrane, 1. thus What is the lifespan of a WBC? 13-20 days initiating phagocytosis. (might be asked in the exam) Bacterial membranes have antigen, thus there will be an antigen-antibody MACROPHAGES are the end-stage product of complex. monocytes that enter the tissues from the blood. OPSONIZATION - The process by which a They are much more powerful phagocytes than pathogen is selected for phagocytosis. neutrophils, often capable of phagocytizing as many as 100 bacteria Called the most versatile form of phagocytes in the body. BATCH 2028 1A 3 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 ○ Fixed macrophage - inside the organ tissues Macrophage are found in the different parts of the body ○ Microglial cells - brain ○ Alveolar macrophage - lungs ○ Histiocyte - tissues ○ Kupffer cells - liver ○ Ostial macrophage - bone Located in tissues especially tissues containing Figure 7. Phases of phagocytosis large numbers of particles, toxins or other amounts of foreign substances that need to be NEUTROPHILS AND MACROPHAGES CAN KILL destroyed. BACTERIA Figure 8. Formation of oxidizing agents by the enzymes in the membranes of phagosomes or in peroxisomes Figure 9. Differentiation of a monocyte to different types of cells: Killing effect results from several oxidizing agents formed by enzymes in the membrane of the phagosome or by a special organelle called the peroxisome. ○ Superoxide (O2~) ○ Hydrogen peroxide (h2O2) ○ Hydroxyl ions (OH~) ○ Lysosomal enzymes Myeloperoxidase – catalyzes the reaction between H2O2 and chloride ions to form hypochlorite, which has strong bactericidal effects. There are bacteria with protective coats that resist the digestive enzyme. In addition the neutrophils and macrophage have other oxidizing agents that can kill the bacteria. These damage the structural and functional Figure 10. Different fixed macrophages in their respective components of the bacterial therefore inhibiting locations. and kill the pathogens. Functions: Difference between bactericidal and Removal of foreign objects and toxins bacteriostatic? Formation of new RBCs and WBCs Bactericidal - kill the bacteria Destruction of senescent RBCs Bacteriostatic - deactivates the Formation of bile pigments bacteria, but does not kill it, Storage of iron weaken. Clearance of heparin via heparinase. III. MONOCYTE-MACROPHAGE CELL IV. INFLAMMATION SYSTEM (RETICULOENDOTHELIAL When tissue injury occurs, whether caused by SYSTEM) bacteria, trauma, chemicals, heat or any other More known as Reticuloendothelial System phenomenon, multiple substances are released (RES), by the bruised tissues and cause dramatic Just the combination of the monocyte, mobile secondary changes in the surrounding macrophage, and the fixed macrophage and undamaged tissues. the specialized endothelial cells in the bone The entire complex tissue change is called marrow, in the spleen and lymph nodes. INFLAMMATION. ○ Mobile macrophage - freeflowing It is the body’s response to infection or injury. BATCH 2028 1A 4 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 Function: To destroy or inactivate foreign Inflammatory responses begin hours of invaders and to set stage for tissue repair. infection or formation of wound, characterized Chemokine prompts the neutrophils to undergo by heat, redness, swelling, tenderness, and diapedesis and go to the site of inflammation pain. and do phagocytosis. Heat is due to increased blood flow because Different products of complement cascade, of vasodilation and increased permeability of treatments, etc releases blood protein and the capillaries, allowing leakage of large clotting elements the blood and clotting begin quantities of fluid, resulting to swelling or at the wound site. This will prevent pathogens edema. from spreading via blood. It will continue until Extravasation of leukocytes towards the site of the pathogen is eliminated and the wound is injury and the action of prostaglandin (induce repaired. fever) causes tenderness or pain. INFLAMMATORY PROCESS Figure 13. Cardinal Signs of Inflammation Cardinal signs of inflammation: Figure 11. Process of inflammation - Rubor: Redness In injury, the resident tissue macrophage acts - Calor: Heat first. - Tumor: Swelling Next, mast cells and the circulating basophils - Dolor: Pain and Tenderness release a chemical called histamine. This - Functio Laesa: Loss of function histamine causes local vasodilation and increased capillary permeability to cause PURPOSE OF INFLAMMATION recruitment of the leukocytes to the inflamed region. Platelets cascade coagulation are now activated and release blood protein and clotting elements from the blood and clotting begins at the wound site. This will prevent pathogens Figure 14. Process of Extravasation from spreading via blood. Inflammatory response continues until the Allows the body to defend itself from foreign materials are eliminated and the wound invading organisms is repaired. ○ The increase in vascular diameter, and the activated endothelial cells, results in CHARACTERISTICS OF INFLAMMATION leukocytes being able to attach to the endothelium, and then migrate into the tissues where they can attack pathogens. Induces Local Blood Clot ○ This creates a physical barrier preventing the infection from spreading into the bloodstream. Promotes Repair of Injured Tissue Figure 15. (left) Blood clotting beneath the damaged tissue; (right) Figure 12. Characteristics of inflammation Tissue repair. BATCH 2028 1A 5 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 blood cells, particularly the neutrophils, are V. THE “WALLING-OFF” EFFECT elevated in the blood. It is evident when doing a One of the first results of inflammation is to Complete Blood Count (CBC), usually there is “wall off” areas of injury from the remaining an overwhelming WBC and tremendous tissues. amount of neutrophils in the circulation. The tissue spaces and the lymphatics in the inflamed area are blocked by fibrinogen clots, NEUTROPHILIA so that after a while, fluid barely flows through Within a few hours after the onset of acute, the spaces. severe inflammation, the number of neutrophils in the blood increases 4-5 the normal (about 15 This walling-off process delays the spread of 000 to 25 000 neutrophils per microliter). bacteria or toxic products. Caused by products of inflammation that enter the bloodstream, transported to the bone marrow, and act on the stored neutrophils of VI. FIRST LINE OF DEFENSE: TISSUE the marrow to mobilize these into the MACROPHAGE circulating blood and makes even more neutrophils available to the inflamed area. Normal WBC count: 4,500-11,000 Within minutes after inflammation begins, the macrophages already present in the tissues immediately begin their phagocytic VIII. THIRD LINE OF DEFENSE: SECOND actions. (ex: histocytes in the SQ tissues, MACROPHAGE INVASION INTO THE alveolar macrophages in the lungs, INFLAMED TISSUE microglia in the brain etc. immediately begin their phagocytic actions.) Along with the invasion of neutrophils, Next, many of the previously sessile monocytes from the blood enter the inflamed macrophages break loose from their tissue and enlarge to become macrophages. attachments and become mobile, forming After several days or weeks, the macrophages the first line of defense against infection dominate the phagocytic cells of the inflamed during the first hour or so. area because of greatly increased bone marrow production of new monocytes VII. SECOND LINE OF INVASION: Monocytes are usually seen in chronic inflammation. After several days to several NEUTROPHIL INVASION OF THE weeks, the macrophage finally comes to INFLAMED AREA dominate as the main phagocytic cell in the PROCESS OF INVASION OF NEUTROPHILS TO inflamed area, because of the increased bone THE INFLAMED AREA marrow production of the granulocyte and 1. They cause increased expression of monocyte. adhesion molecules: selectins and intercellular adhesion molecule- 1 (ICAM-1) on the surface of endothelial IX. FOURTH LINE OF DEFENSE: cells in the capillaries and venules. INCREASED PRODUCTION OF GRANULOCYTES AND MONOCYTES BY THE BONE MARROW 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 Figure 16. Process of invasion of neutrophils. produce these cells in tremendous quantities for months and even years, sometimes at a rate 20 to 50 times normal (specially in chronic 2. They cause the intercellular attachments inflammation). - which is not good because between the endothelial cells of the there should be a control of macrophage. capillaries and small venules to loosen, allowing openings to be large enough for The fourth line of defense is an increase also in neutrophils to crawl through directly from the production of granulocyte and monocyte the blood into tissue spaces by diapedesis. which is just for replacement. Can also cause chemotaxis which is the process of attraction of the neutrophils going to the site of inflammation or infection. The reason why is that if there is infection or inflammation, you would see that the white BATCH 2028 1A 6 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 pus). After the infection has been suppressed, the CONTROL OF MACROPHAGE 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. - Which means, there is no more trace of skin injury because of the tissue repair. The pus usually is whitish-yellow, yellow, or greenish-colored. This is because neutrophils also contain a pigment called Myeloperoxidase, which is also an antibacterial protein. If the infection is caused by pseudomona aeruginosa, the bacteria also contains a pigment called Pyocyanin. “Phyo” means pus. Pyocyanin is a green pigment that is produced by the pseudomonas aeruginosa. If blood gets inside the pus, the color has a red tinge. XI. EOSINOPHILS Eosinophils are weak phagocytes and also exhibits chemotaxis. Eosinophils are produced in large numbers in people with parasitic infections, and they Figure 17. Control of Macrophages migrate into tissues diseased by parasites. Example of parasites: Ascaris This cause of increased production of Eosinophils attach themselves to the juvenile granulocytes and monocytes by the bone forms of the parasite and kill many of them by: marrow is mainly the three colony-stimulating 1. Releasing hydrolytic enzymes from their factors, one of which, GMCSF, G-CSF and granules, which are modified lysosomes. M-CSF 2. Releasing highly reactive forms of oxygen Combination of TNF, IL-1, and that are especially lethal to parasites. colony-stimulating factors provides a powerful Eosinophils are associated in allergic feedback mechanism that begins with tissue processes. They also have a special propensity inflammation and proceeds to formation of to collect in tissues in which allergic reactions large numbers of defensive WBCs that help occur. remove the cause of the inflammation. Both mast cells and basophils release an eosinophil chemotactic factor that causes eosinophils to migrate toward the inflamed X. FORMATION OF PUS allergic tissue. Also phagocytic however it is more weaker Consists of 2% of blood leukocytes Also seen when there is parasitic infection and also allergic reaction. Eosinophils are also seen in the peribronchial tissue on patients with asthma or in the skin after an allergic skin reaction How do eosinophils promote phagocytosis even if they are weaker phagocytic cells compared to neutrophils and macrophages? Eosinophils attach themselves to the juvenile form - immature or young ones - of parasites and they kill them by releasing Figure 18. Formation of pus hydrolytic enzymes from eosinophilic When neutrophils and macrophages engulf granules which are modified microcytes. large numbers of bacteria and necrotic tissue, Eosinophils also have a high reactive control of essentially all the neutrophils and many, if not oxygen which are refound in the parasite and most, of the macrophages eventually die. they releases the MBP - the major basic protein After several days, a cavity is often excavated - which is a highly larvicidal polypeptide in the inflamed tissues. Both mast cells and basophils also releases This cavity contains varying portions of necrotic eosinophil chemotactic factor that causes tissue, dead neutrophils, dead macrophages, eosinophils to migrate toward the inflame and tissue fluid (the mixture is commonly called allergic tissue BATCH 2028 1A 7 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 Some drugs such as Chloramphenicol (an XII. BASOPHILS antibiotic), Thiouracil (used to treat What is the difference between basophils and thyrotoxicosis) and even various barbiturate mast cells? hypnotics on rare occasions cause Leukopenia ○ Usually they go together but they have Aplasia - means that the bone marrow can no different functions. Both mast cells and longer create, produce or unable to store red basophils because they both release blood cells or white blood cells heparin and histamine. They play an important role in allergic reactions. XIV. LEUKEMIA The basophils in the circulating blood are similar to the large tissue mast cells located A disease or malignancy that characterized by immediately outside many of the capillaries in greatly increased numbers of WBCs in the the body. circulating blood Both release histamine, smaller amt. of Uncontrolled production of WBCs can be bradykinin and serotonin (allergic reactions, caused by cancerous mutation of a pain, emotions). myelogenous or lymphogenous cell. Both play an important role in allergic reactions Although you have a lot of WBC but they are all Immunoglubulin E (IgE) has a special abnormal. propensity to attach to mast cells & basophils. Leukemia is a cancer of the body’s blood In resulting attachment of antigen to antibody forming tissue in the bone marrow or the causes the mast cell or basophil to rupture and lymphatic system. release large amount of histamine, bradykinin, serotonin, heparin, slow-reacting substance of TWO TYPES OF LEUKEMIA anaphylaxis & a number of lysosomal enzymes. These substances cause a local vascular and A. LYMPHOCYTIC LEUKEMIA (ACUTE LL OR tissue reactions that cause allergic CHRONIC LL) manifestation. Caused by cancerous production of lymphoid Basophils in the circulating blood are similar to cells, beginning in lymph nodes or other mast cells which is in the tissues lymphocytic tissue and spreading to other Both mast cells and basophils delebirate areas of the body hepamine into the blood B. MYELOGENOUS LEUKEMIA (AML OR CML) Begins by cancerous production of young and myelogenous cells in the bone marrow and then spreads throughout the body so that WBCs are produced in many extramedullary tissues especially in the lymph nodes, spleen and liver Different cells under myelocytic series: erythrophyls, eosinophils, basophils, and monocytes Acute - less than 6 months. If it progresses beyond 6 months that is chronic leukemia EFFECTS OF LEUKEMIA The first effect of leukemia is metastatic growth Figure 19. Anaphylactic reaction of leukemic cells in abnormal areas of the body - leukemic cells from the bone marrow may XIII. LEUKOPENIA invade the surrounding bone, causing pain and a tendency for bones to fracture easily Penia = Lacking There’s development of infection, severe In which bone marrow produces very few anemia, and bleeding tendency caused by WBCs. thrombopenia. These effects result mainly from If your body lacks WBC, your body will not be displacement of the normal bone marrow and fully protected. lymphoid cells by the nonfunctional leukemia Within 2 days after the bone marrow stops cells producing WBCs, ulcers may appear in the Another important effect of leukemia on the mouth and colon. body is excessive use of metabolic substrate Bacteria from the ulcers rapidly invade by the growing cancerous cells. surrounding tissues and the blood. Without The leukemic tissues reproduce new cells so treatment, death often ensues in less than a rapidly that tremendous demands are on the week after acute total leukopenia begins. body reserves for foodstuff, amino acids, and Irradiation of the body by x-rays or gamma rays, or exposure to drugs and chemicals that vitamins. contain benzene or anthracene nuclei, is likely to cause aplasia of the bone marrow. BATCH 2028 1A 8 PHYSIOLOGY LC6: RESISTANCE TO BODY INFECTION Dr. PASCUA, E. 09/16/2024 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 Even if we have enough WBC but are abnormal and non-functional of course the development of infection, anemia and bleeding - cause by thrombocytopenia - is the effect of results from the displacement of the normal bone marrow and pentosis by non-functional lipid Reference(s): Hall, J.F. (2016). Guyton and Hall: Textbook of Medical Physiology. (13th ed.). ELSEVIER. Dr. Pascua’s Powerpoint Presentation. BATCH 2028 1A 9