Hematology part 3.pdf

Slide 1 Hematology WBC White Blood Cells (Leukocytes) Fatima Daoud, MD, PhD Slide 2 Granulocytes Neutrophils Non- Granulocytes Monocytes Eosinophils Lymphocytes Basophils E N B L M Boron Medical Physiology Slide 3 WBC CLASSIFICATION WHITE BLOOD CELLS Neutrophils (62%) LEUKOCYTE...

Slide 1 Hematology WBC White Blood Cells (Leukocytes) Fatima Daoud, MD, PhD Slide 2 Granulocytes Neutrophils Non- Granulocytes Monocytes Eosinophils Lymphocytes Basophils E N B L M Boron Medical Physiology Slide 3 WBC CLASSIFICATION WHITE BLOOD CELLS Neutrophils (62%) LEUKOCYTES Hematology Granulocytes (65%) Eosinophils (2.3%) Basophils (0.4%) Monocytes (5%) Lymphocytes (30%) Tissue macrophages Slide 4 Created with Biorender **The granulocytes and monocytes are formed only in the bone marrow. **Lymphocytes and plasma cells are produced mainly in the various lymphogenous tissues— especially the lymph glands, spleen, thymus, tonsils, and various pockets of lymphoid tissue elsewhere in the body, such as in the bone marrow. **The white blood cells formed in the bone marrow are stored within the marrow until they are needed in the circulatory system. when the need arises, various factors cause them to be released. **Normally, about three times as many white blood cells are stored in the marrow as circulate in the entire blood. This represents about a 6-day supply of these cells **The life of the granulocytes after being released from the bone marrow is normally 4 to 8 hours circulating in the blood and another 4 to 5 days in tissues where they are needed Slide 5 Blood function: Protection White blood cells work together in two ways to prevent disease: (1) by actually destroying invading bacteria or viruses by phagocytosis. (Neutrophils and macrophages) (2) by forming antibodies and sensitized lymphocytes, which may destroy or inactivate the invader. Slide 6 Granulocyte • The granulocytes are formed only in the bone marrow. • They stored within the marrow until they are needed in the circulatory system. • The life of the granulocytes after being released from the bone marrow is normally 4 to 8 hours circulating in the blood and another 4 to 5 days in tissues where they are needed. • In times of serious tissue infection, this total life span is often shortened. **In times of serious tissue infection, this total life span is often shortened to only a few hours because the granulocytes proceed even more rapidly to the infected area, perform their functions, and, in the process, are themselves destroyed. Slide 7 Monocyte/macrophage • The monocytes are formed only in the bone marrow. • The monocytes also have a short transit time, 10 to 20 hours in the blood. • Once in the tissues, they swell to much larger sizes to become tissue macrophages (can live for months). Slide 8 Actions of Phagocytic Cells 1. 2. 3. 4. 5. 6. Margination Tight binding Diapedesis Chemotaxis Ameboid Motion (pseudopodia) Phagocytosis **The neutrophils are mature cells that can attack and destroy bacteria even in the circulating blood. Conversely, the tissue macrophages begin life as blood monocytes, which are immature cells while still in the blood and have little ability to fight infectious agents at that time. However, once they enter the tissues, they begin to swell—sometimes increasing their diameters as much as fivefold—to as great as 60 to 80 micrometers, a size that can barely be seen with the naked eye. These cells are now called macrophages, and they are extremely capable of combating disease agents in the tissues. ** Slide 9 Actions of Phagocytic Cells **Neutrophils and monocytes can squeeze through the pores of the blood capillaries by diapedesis. **Both neutrophils and macrophages can move through the tissues by ameboid motion. **Many different chemical substances in the tissues cause both neutrophils and macrophages to move toward the source of the chemical. This phenomenon is called chemotaxis. **phagocytosis, which means cellular ingestion of the offending agent. ** Slide 10 Slide 11 Slide 12 Phagocytosis Phagocytes must be selective and likelihood of phagocytosis is increased when : 1. If the surface is rough, the likelihood of phagocytosis is increased. 2. Most dead tissues and foreign particles have no protective protein coats. 3. The antibodies adhere to the bacterial membranes and thereby make the bacteria especially susceptible to phagocytosis (opsonization) Slide 13 Phagocytosis How does a phagocytic cell kill a microorganism? • Enzymatic digestion • Hypochlorite (myeloperoxidase) • Reactive oxygen metabolites superoxide anion hydrogen peroxide hydroxyl radicals Slide 14 Slide 15 Neutrophil • Mature cells that can attack and destroy bacteria even in the circulating blood. • Not capable of phagocytizing particles much larger than bacteria. Monocyte/macrophage • Monocyte are immature cells while still in the blood and have little ability to fight infectious agents at that time. • They have the ability to engulf much larger particles (RBC). • Macrophages are much more powerful phagocytes. • Can extrude the residual products and often survive and function for many more months. Slide 16 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 is called the reticuloendothelial system. • Generalized phagocytic system located in all tissues, especially in those tissue areas where large quantities of particles, toxins, and other unwanted substances must be destroyed. Slide 17 Monocyte-Macrophage Cell System (Reticuloendothelial System) • Tissue Macrophages in the Skin and Subcutaneous Tissues (Histiocytes). • Macrophages in the Lymph Nodes. • Alveolar Macrophages in the Lungs. • Macrophages (Kupffer Cells) in the Liver Sinusoids. • Macrophages of the Spleen. • Macrophages in bone Marrow. Slide 18 Eosinophils • They form about 2 percent of all the blood leukocytes. • Eosinophils are weak phagocytes. • They are often produced in large numbers in people with parasitic infections. • Eosinophils attach themselves to the parasites by way of special surface molecules and release substances that kill many of the parasites. • Eosinophils also have a special propensity to collect in tissues in where allergic reactions occur. Slide 19 Basophils • ~ 0.5% of total white blood cells • Similar to the large tissue mast cells located immediately outside many of the capillaries in the body. • They express IgE antibody on the surface and antigen binding causes rupture of basophil and release large quantities of intracellular granules. • The mast cells and basophils release histamine, heparin, as well as smaller quantities of bradykinin and serotonin. Slide 20 Hematology Lymphocytes ▪ Lymphocytes are produced mainly in the various lymphogenous tissues. ▪ Some of the lymphocytes enter the circulatory system continually. ▪ Lymphocytes have life spans of weeks or months, depending on the body’s need for these cells. Slide 21 Immunity Innate Acquired CellMediated Humoral ** Immunity is capability of human body to resist almost all types of organisms or toxins that tend to damage the tissues and organs. ** An antigen is a substance that can induce an immune response when introduced into an immunocompetent host and that can react with the antibody produced from that response. Slide 22 Innate Vs. Acquired (Adaptive) • Results from general processes. • Results from processes directed towards specific disease organisms. • Does not develop until the body is first attacked by a bacterium, virus, or toxin, often requiring weeks or months to develop the immunity. Slide 23 Innate Vs. Acquired (Adaptive) • Phagocytosis • Acid secretions of the stomach and the digestive enzymes. • Skin (tight junctions). • lysozyme • Basic polypeptides • Complement system • Natural killer lymphocytes • Antibodies • Activated lymphocytes Slide 24 The innate immune system aims to : ▪ Prevent infection. ▪ Eliminate invader pathogens. ▪ Stimulate the acquired immune response. Pathogens Innate Immune Responses Adaptive immune responses Slide 25 Macrophage- activation of T-lymphocyte • Most invading organisms are first phagocytized and partially digested by the macrophages, and the antigenic products are liberated into the macrophage cytosol. • The macrophages then pass these antigens by cell-to-cell contact directly to the lymphocytes, thus leading to activation of the specified lymphocytic clones. • The macrophages secrete interleukin-1 that promotes further growth and reproduction of the specific lymphocytes. Slide 26 Skin Macrophage- activation of lymphocyte Activated T- helper cell Microbes interleukin-1 Tissue macrophage Innate Immune Response Lymph Node Adaptive Immune Response Slide 27 Slide 28 Basic Types of Acquired Immunity—Humoral and Cell-Mediated • Humoral (B-cell immunity) • Circulating antibodies, which are γ-globulin molecules in the plasma that are capable of attacking the invading agent. • Cell-Mediated (T-cell immunity) • Achieved through the formation of large numbers of activated T lymphocytes that are specifically crafted in the lymph nodes to destroy the foreign agent. • (1) helper T cells (2) cytotoxic T cells (3) suppressor T cells ** Most antigens activate both T lymphocytes and B lymphocytes at the same time. Slide 29 Created with Biorender.com Before becoming exposed to a specific antigen, B lymphocyte clones lie latent in lymphoid tissue. When a foreign antigen enters the lymphoid tissue, macrophages phagocytize it and present it to T cells resulting in the formation of activated helper T cells. These helper cells release chemicals (known as lymphokines) that activate the specific B lymphocytes. Indeed, without the assistance of these helper T cells, the amount of antibodies produced by B lymphocytes is usually minimal. **The plasmablasts then begin to divide at a rate of about once every 10 hours for about nine divisions, giving in 4 days a total population of about 500 cells for each original plasmablast. The mature plasma cell then produces gamma globulin antibodies at an extremely rapid rate—about 2000 molecules per second for each plasma cell. **The antibodies are secreted into the lymph and carried to the circulating blood. Slide 30 Humoral immunity Cell-mediated immunity Microbe Extracellular microbes Responding lymphocytes B lymphocyte Phagocytosed Microbes in macrophage Helper T lymphocyte Intracellular Microbes (e.g., viruses) Replicating within Infected cell Cytolytic T lymphocyte Secreted antibody Effector mechanism Functions Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Block infections and eliminate extracellular microbes Activate macrophages to kill phagocytosed microbes Kill infected cells and eliminate reservoirs of infection Slide 31 Formation of Memory cells (B-lymphocyte) • Moderate numbers of new B lymphocytes similar to those of the original clone. • They also circulate throughout the body to populate all the lymphoid tissue; immunologically, however, they remain dormant until activated once again by a new quantity of the same antigen Slide 32 Primary Response and Secondary Response. primary response: • 1-week delay • weak potency • short life Slide 33 Mechanisms of Action of Antibodies • Antibodies act mainly in two ways to protect the body against invading agents: (1) by direct attack on the invader (2) by activation of the “complement system” that then has multiple means of its own for destroying the invader. Slide 34 Mechanisms of Action of Antibodies Bioninja.com These direct actions of antibodies attacking the antigenic invaders often are not strong enough to play a major role in protecting the body against the invader Slide 35 Complement System for Antibody Action • A system of about 20 proteins, many of which are enzyme precursors. • All these are present normally among the plasma proteins in the blood, as well as among the proteins that leak out of the capillaries into the tissue spaces. • The enzyme precursors are normally inactive Slide 36 Complement System for Antibody Action C3b C5b6789 Lysis C3a, C4a, and C5a Activation of mast cells and basophils. C5a Chemotaxis Slide 37 Tolerance of the Acquired Immunity System to One’s Own Tissue most tolerance develops during preprocessing of T lymphocytes in the thymus and of B lymphocytes in the bone marrow. The reason for this belief is that injecting a strong antigen into a fetus while the lymphocytes are being preprocessed in these two areas prevents development of clones of lymphocytes in the lymphoid tissue that are specific for the injected antigen Slide 38 Failure of the Tolerance Mechanism Causes Autoimmune Diseases • Body becomes immunized against tissues in the joints and heart, especially the heart valves, after exposure to a specific type of streptococcal toxin that has an epitope in its molecular structure similar to the structure of some of the body’s own self-antigens; Physiopedia.com Slide 39 Immunization (vaccination) by Injection of Antigens Dead organisms (are no longer capable of causing disease) Toxins (treated with chemicals so that their toxic nature has been destroyed even though their antigens for causing immunity are still intact). Attenuated live organisms (organisms either have been grown in special culture media or have been passed through a series of animals until they have mutated enough that they will not cause disease but do still carry specific antigens required for immunization) Slide 40 Active Immunity Passive Immunity • The person’s own body develops either antibodies or activated T cells in response to invasion of the body by a foreign antigen. • Infusing antibodies, activated T cells, or both obtained from the blood of someone else or from some other animal that has been actively immunized against the antigen. • last in the body of the recipient for 2 to 3 weeks. Slide 41 Tetanus is an infection caused by bacteria called Clostridium tetani. When these bacteria enter the body, they produce a toxin that causes painful muscle contractions Active Immunity • Vaccination by injecting tetanus toxin. • Every 10 years Rmi.edu.pk Passive Immunity • Human Tetanus Immunoglobulin (IgG) • Immediate prophylaxis after tetanus prone injuries in patients not adequately vaccinated. Slide 42 Allergies • Allergies occur when your immune system reacts to a foreign substance — such as pollen, bee venom or pet dander — or a food that doesn't cause a reaction in most people Slide 43 Hematology Inflammation Inflammation Slide 44 Inflammation • The complex of changes that accompany tissue damage including vascular and cellular events that aim to clean up any cellular debris or pathogen and initiate repair. Slide 45 Types/causes of Inflammation: Infectious Infectious Autoimmune inflammation ✓Physical trauma ✓Chemical trauma Heat metabolic inflammation Slide 46 Signs of Inflammation 5 Signs of Inflammation: Pain, Heat, Redness, Swelling, and Loss of Function. By Lana Barhum Slide 47 Inflammation is characterized by: 1. Vasodilation of the local blood vessels. Relaxation of smooth muscle Slide 48 Inflammation is characterized by: 2. Increased permeability of the capillaries. Slide 49 Inflammation is characterized by: 2. Increased permeability of the capillaries. Bradykinin Nerve Slide 50 Inflammation is characterized by: 3. Migration of large numbers of granulocytes and monocytes into the tissue. Leukocytosis Slide 51 Inflammation is characterized by: 4. Increased amounts of fibrinogen and other proteins leaking from the capillaries. Walling-Off Fibrin sparks inflammation in the oral mucosa, Volume: 374, Issue: 6575, Pages: 1559-1560, DOI: (10.1126/science.abn0399) Slide 52 Erythrocyte sedimentation rate (ESR) Mindray.com Slide 53 ➢ (A) A fibrin clot is formed and inflammatory cells enter the wound site. ➢ (B) Re-epithelialization ➢ (C) Remodeling is the final stage of wound healing. ECM remodeling factors modulate and revise the scar tissue. Almine JF, Wise SG, Weiss AS. Elastin signaling in wound repair. Birth Defects Res C Embryo Today. 2012 Sep;96(3):248-57. The first phase is dominated by thrombin cleavage of fibrinogen integrated with an acute inflammatory response that functions to contain tissue damage, stop the loss of blood, and prevent microbial infection. The second phase is dominated by plasmin dissolution of fibrin and other matrix proteins integrated with reparative inflammatory cells working to remodel and repair damaged tissue Slide 54 Tissue Macrophage Is a First Line of Defense Against Infection • Within minutes after inflammation begins, the macrophages already present in the tissues, begin their phagocytic actions. • The first effect is rapid enlargement of each of these cells. • Next, many of the previously sessile macrophages break loose from their attachments and become mobile. • The numbers of these early mobilized macrophages often are not great, but they are lifesaving. Slide 55 Neutrophil invasion of the Inflamed Area Is a 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. • This is caused by inflammatory cytokines (e.g., TNF, IL-1) produced by the inflamed tissues and macrophages Acute phase reactants: C-reactive protein NinjaNerd: inflammation Slide 56 Acute Increase in Number of Neutrophils in the Blood—“Neutrophilia.” • 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 • Neutrophilia is caused by products of inflammation that enter the blood stream, are transported to the bone marrow, and there act on the stored neutrophils of the marrow to mobilize these into the circulating blood. Boron, Medical Physiology Slide 57 Second Macrophage Invasion into the Inflamed Tissue Is a Third Line of Defense Buildup of macrophages in the inflamed tissue area is much slower than that of neutrophils, requiring several days to become effective. ➢ The number of monocytes in the circulating blood is low. ➢ The storage pool of monocytes in the bone marrow is much less than that of neutrophils. ➢ Monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes. **monocytes from the blood enter the inflamed tissue and enlarge to become macrophages. However, the number of monocytes in the circulating blood is low: Also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils. **even after invading the inflamed tissue, monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes; only then do they acquire the full capacity of tissue macrophages for phagocytosis **As already pointed out, macrophages can phagocytize far more bacteria (about five times as many) and far larger particles, including even neutrophils themselves and large quantities of necrotic tissue, than can neutrophils. Also, the macrophages play an important role in initiating the development of antibodies Slide 58 Second Macrophage Invasion into the Inflamed Tissue Is a Third Line of Defense 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. **monocytes from the blood enter the inflamed tissue and enlarge to become macrophages. However, the number of monocytes in the circulating blood is low: Also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils. **even after invading the inflamed tissue, monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes; only then do they acquire the full capacity of tissue macrophages for phagocytosis **As already pointed out, macrophages can phagocytize far more bacteria (about five times as many) and far larger particles, including even neutrophils themselves and large quantities of necrotic tissue, than can neutrophils. Also, the macrophages play an important role in initiating the development of antibodies Slide 59 Increased Production of Granulocytes and Monocytes by the Bone Marrow Is a Fourth Line of Defense. • Normally, 75% of the cell production in the bone marrow is directed toward white blood cell, and only 25% towards red blood cells. (?) • 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. ?? In the circulation the number of RBCs is much more than the number of WBCs? because the half- life of WBCs is much shorter than the half-life of RBCs Slide 60 Formation of Pus • An exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation. • Consists of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid. • After the infection has been suppressed, the dead cells and necrotic tissue in the pus gradually autolyze over a period of days, and the end products are eventually absorbed into the surrounding tissues and lymph until most of the evidence of tissue damage is gone.