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Blood 1 Blood Blood is not an epithelial tissue, and it’s not loose or dense connective tissue; it’s classified as a “special connective tissue”. You have about 5 liters of blood (30 pints), but that is only half of the body fluid. The other half includes fluid around each cell, and joint fluids, CSF, GI juices, etc. 2 Blood plasma circulates outside of the blood vessels too! PLASMA EXTRACELLULAR FLUID ↑↓ ↓↑ ↓↑ SYNOVIAL FLUIDS GI Organs CSF 3 Blood consists of the following: Plasma Formed Elements – Red blood cells – White blood cells – Platelets 4 FUN FACTS In one day, your blood travels nearly 12,000 miles. Your heart beats around 35 million times per year. Your heart pumps a million barrels of blood during the average lifetime -enough to fill three supertankers. If an artery is cut, blood will shoot out 30 feet. 5 Plasma Plasma is what the blood cells float around in. If you spin a blood sample in a test tube, the red blood cells sink to the bottom, and you’ll see the yellow plasma on top, and a thin “buffy coat” in the middle where the white blood cells are. Some people who need blood just need the packed RBCs (anemia), some need the platelets (hemophelia), others need the plasma (burn patients), and some need whole blood, which is both plasma and RBCs (hemorrhage). If blood is donated to a Children’s Hospital, they can save 5 children with one pint of adult blood. 6 Overview: Composition of Blood Figure 17.1 7 8 PLASMA CONTENTS Water (90%) Dissolved substances (10%) – Proteins – Nutrients – – – Albumin (egg white). Most common protein in blood (homeostasis) Antibodies Clotting factors called fibrinogen and fibrin. Lipoproteins (move fats through blood: HDL, LDL) Glucose (main energy source) Amino Acids (builds proteins) Wastes (urea) Gases (O2, CO2, Nitrogen) Electrolytes = ions (Na+, K+, Cl-, Ca++) 9 10 Blood Cells 11 ERYTHROCYTES (Red blood cells) 30 trillion RBC’s in 5 Liters of blood Like a doughnut with the hole not fully cut out. – Biconcave to increase surface area – These are among the smallest cells in the body – They have no nucleus; cannot reproduce or get cancer – Filled with hemoglobin (Hgb), which carries O2 throughout the body. Oxygenated Hgb is bright red, deoxy Hgb is deeper red, almost a bluish-purple. 12 Erythrocytes 13 Hemoglobin Molecule 14 Hemoglobin Molecule 15 ERYTHROCYTES: – Average life span is 120 days. Old ones are destroyed in the spleen and liver, and Hgb and iron are recycled. – There are 30 trillion RBCs in the body. – About 25% of the body’s cells are RBCs. – 2.4 million RBCs are destroyed per second so that’s how many are made per second. – 8.6 billion RBCs are made each hour. – 200 billion are made each day. – They are made in the red bone marrow (spongy bone). 16 Erythropoiesis Erythropoiesis is the process of making new red blood cells. It is stimulated by increased tissue demand for oxygen. The kidneys sense the low oxygen levels, and they make a hormone called erythropoietin that stimulates erythropoiesis. 17 18 Disorders of RBCs Polycythemia Anemia – Too few RBC’s – Iron deficiency – Hemorrhagic anemia (person lost blood) – Hemolytic anemia (immune disorder, infection, blood transfusion) G6PD deficiency – Hemoglobin abnormalities Pernicious (Megaloblastic) anemia (lack of vitamin B12 or intrinsic factor) Thalassemia Sickle cell disease – Red Blood Cell Membrane disorders Hereditary spherocytosis 19 Polycythemia Too many RBC’s; can cause clots. Need to have blood drawn frequently (therapeutic phlebotomy). Cannot use the blood for donation. 20 21 ANEMIA Any condition of RED BLOOD CELLS in which the blood’s capacity for carrying oxygen is diminished. HYPOXIA is lack of oxygen to tissues. – It can be caused from: Ischemia (reduced blood flow to a tissue) Malfunctioning hemoglobin Lack of iron in the hemoglobin Increasing altitude – Payne Stewart’s plane: all died from hypoxia 22 Anemia Characteristic sign of anemia: see reticulocytes in the blood (immature red blood cells). Remnants of the nucleus are still in the cell. 23 Reticulocytes 24 Anemia can be caused by many things. One type of anemia is from too few RBC’s. 25 Anemia can also be caused from Iron Deficiency 26 IRON DEFICIENCY ANEMIA that was treated with blood transfusion These are the healthy RBCs from blood transfusion 27 Hemolytic Anemia Hemolysis means rupture of RBC’s. – Hereditary (born with the genes that cause the disease) Autoimmune disorders G6PD deficiency – Acquired Infections (malaria and ebola) Receiving the wrong blood type in a transfusion. 28 G6PD Deficiency Hereditary, X-linked; almost all are males G6PD is an enzyme which is important for RBC metabolism. G6PD is the most common human enzyme defect. A person with this develops hereditary (NOT acquired) hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications, chemicals, or ingestion of fava beans. 29 G6PD Deficiency antimalarials (a type of medication used to prevent and treat malaria, such as quinine) sulfonamides (a medication used for treating certain types of infection) aspirin (used for relieving fever, pain, and swelling) some nonsteroidal anti-inflammatory medications (NSAIDs) 30 G6PD Deficiency The condition is most commonly seen in Africa, where it can affect up to 20 percent of individuals. There is no cure for the condition, but in severe cases, a blood transfusion may be necessary. Individuals can recover from the hemolysis caused by G6PD deficiency on their own, but severe hemolytic events do occur. Close monitoring of these episodes is critical. 31 Disorders of RBCs Polycythemia Anemia – Too few RBC’s – Iron deficiency – Hemorrhagic anemia (person lost blood) – Hemolytic anemia (immune disorder, infection, blood transfusion) G6PD deficiency – Hemoglobin abnormalities Pernicious (Megaloblastic) anemia (lack of vitamin B12 or intrinsic factor) Thalassemia Sickle cell disease – Red Blood Cell Membrane disorders Hereditary spherocytosis 32 HEMOGLOBINOPATHIES Pernicious anemia (megaloblastic anemia) Thalassemia Sickle Cell Disease 33 Pernicious anemia (megaloblastic anemia) Caused by lack of vitamin B12 or intrinsic factor When a person has gastric bypass surgery, the stomach is no longer able to produce intrinsic factor, which is needed to absorb vitamin B12, which is needed to make hemoglobin in RBC’s. Vitamin B12 is found in green leafy vegetables. Without this vitamin, the blood cells are fewer and much larger than normal (megaloblastic). The gastric surgery patient must take vitamin B12 shots or sublingual supplements for the rest of their life. 34 Megaloblastic Anemia (Large RBCs: Note that the small blue lymphocyte is smaller than some of the huge RBCs) 35 Thalassemia A hereditary form of anemia where the RBCs have abnormal hemoglobin that deforms the cells TEAR DROP TARGET CELLS SPHEROCYTE 36 Sickle Cell Disease A hereditary mutation resulting in one valine amino acid substituted for glutamic acid. Present in people with African ancestry more than in other groups, and is always characterized by sickled erythrocytes. The sickle shape helps prevent malaria infections, but it also causes blood clots. VIDEO 37 Sickle Cell Anemia SICKLE CELL 38 39 CELL MEMBRANE PROBLEMS Hereditary Spherocytosis 40 Hereditary spherocytosis The red blood cells shrink over time due to problems with the red blood cell membrane. Many of the RBC’s look small and round. 41 RBC, Hgb, Hct Red blood cell (RBC) count is a count of the actual number of red blood cells per volume of blood. Both increases and decreases can point to abnormal conditions. Hemoglobin (Hgb) measures the amount of oxygencarrying protein in the blood. Hematocrit (Hct) measures the percentage of red blood cells in a given volume of whole blood. 42 Hematocrit A quick screening test for anemia is the hematocrit. A drop of blood is drawn up a small glass capillary tube and the tube is centrifuged to pack the red blood cells at the bottom with the plasma on top. Hematocrit measures the percentage of blood volume that consists of erythrocytes. The hematocrit is the ratio of packed red blood cells to total blood volume. Normal is about 45% (46% for men and 38% for women.) 43 Hematocrit 44 Mean Corpuscular Volume Mean corpuscular volume (MCV) is a measurement of the average size of your RBCs. The MCV is elevated when your RBCs are larger than normal (macrocytic), for example in anemia caused by vitamin B12 deficiency. When the MCV is decreased, your RBCs are smaller than normal (microcytic) as is seen in iron deficiency anemia or thalassemias or hereditary spherocytosis. 45 Mean Corpuscular Hemoglobin Mean corpuscular hemoglobin (MCH) is a calculation of the average amount of oxygen-carrying hemoglobin inside a red blood cell. Macrocytic RBCs are large so tend to have a higher MCH, while microcytic red cells would have a lower value. 46 Mean Corpuscular Hemoglobin Concentration Mean corpuscular hemoglobin concentration (MCHC) is a calculation of how saturated with oxygen each hemoglobin molecule is. How red are the RBCs? Is there an O2 molecule on all 4 heme plates? Or are just two plates occupied with O2? Decreased MCHC values (hypochromia; RBC looks pale) are seen in conditions where the hemoglobin is abnormally diluted inside the red cells, such as in iron deficiency anemia and in thalassemia. Increased MCHC values (hyperchromia; RBC looks too red) are seen in conditions where the hemoglobin is abnormally concentrated inside the red cells, such as in burn patients and hereditary spherocytosis, a relatively 47 rare congenital disorder. Red Cell Distribution Width Red cell distribution width (RDW) is a calculation of the variation in the size of your RBCs. If all the RBCs are the same size, that is a normal RDW. Having a few RBC’s with various shapes is called aniscocytosis. Having many RBC’s with various shapes is called poikilocytosis (thalassemia). In some anemias, such as pernicious anemia and thalassemia, anisocytosis and poikilocytosis causes an increase in the RDW. 48 Blood Doping Blood doping is the practice of boosting the number of red blood cells in the bloodstream by giving an athlete an unnecessary blood transfusion in order to enhance athletic performance. Because such blood cells carry oxygen from the lungs to the muscles, a higher concentration in the blood can improve an athlete’s aerobic capacity and endurance. It is illegal in sports. 49 IOC strips Lance Armstrong of Olympic medal He was the winner of seven straight Tour de France titles. Two months after the France tournament, he won the bronze medal at the 2000 Sydney Games. He confessed to Oprah Winfrey in 2010 to using blood doping during the 2000 olympics. Olympic officials won a suit to have the medal returned. 50 Lance Armstrong (right) 51 BLOOD TYPING: The ABO SYSTEM Blood typing is the technique for determining which specific protein type is present on the RBC membranes. Only certain types of blood transfusions are safe because the cell membranes of the red blood cells carry certain types of proteins that another person’s body will think is a foreign body and reject it. 52 BLOOD TYPING These proteins are called antigens (something that causes an allergic reaction). There are two types of blood antigens: Type A and Type B. A person with Type A antigens on their blood cells has Type A blood. A person with Type B antigens has Type B blood. A person with both types has type AB blood. A person with neither antigen has type O blood. 53 54 BLOOD TYPING If a person with type A blood gets a transfusion of type B antigens (from Type B or Type AB, the donated blood will clump in masses (coagulation), and the person will die. The same is true for a type B person getting type A or AB blood. Type O- blood is called the universal donor, because there are no antigens, so that blood can be donated to anyone. Type AB+ blood is considered the universal acceptor, because they can use any other type of blood. This blood type is fairly rare. The rarest blood type is AB negative. 55 RH FACTOR There is another term that follows the blood type. The term is “positive” or “negative”. This refers to the presence of another type of protein, called the Rh factor. A person with type B blood and has the Rh factor is called B positive. A person with type B blood and no Rh factor is called B negative. 56 RH FACTOR The reason this is so important is that if an Rh- mother has an Rh+ fetus in her womb (from an Rh+ father), her antibodies will attack the red blood cells of the fetus because her body detects the Rh protein on the baby’s red blood cells and thinks they are foreign objects. This is called Hemolytic Disease of the Newborn (HDN). 57 58 HDN This can be prevented if the doctor knows the mother is Rh- and the father is Rh+, because that means the baby has a 50% chance of being Rh+ like the father. Therefore, anytime a mother is Rh-, even if the mother says the father is Rh-, you can’t be sure who the father is, so they will proceed as though the baby may be Rh+. They will give her an injection of a medicine (Rhogam) that will prevent her immune system from attacking the baby. 59 Rhogam The baby does not make the Rh factor until about 18 weeks old. Rhogam is given at 18 weeks into the pregnancy and again within 72 hours after giving birth. It is usually given within 2 hours after giving birth since you can’t trust the patient to return after they leave the hospital. The first baby is not at risk; during the first birth (or miscarriage), the placenta tears away and that’s when the baby’s blood cells get into the mother’s bloodstream. She then forms antibodies against the Rh factor, which are ready to attack the second fetus. Rhogam is given on the first pregnancy, because the mother can never be sure she has not miscarried and did not know she was pregnant. 60 Kell Proteins The Kell protein is another antigen on some people’s RBC’s, similar to the Rh factor. People either have big K or little k proteins. Most people have little kk. If one parent has big K (either Kk or KK), the child can get Hemolytic Disease of the Newborn. This is probably the disease that was in the genes of Henry VIII (probably had Kk), which caused most of his children to become weak and die in infancy. He could only safely have children with those women who were either Kk or KK (about 9% of the population). 61 • Experiments with blood transfusions have been carried out for hundreds of years. • They all failed miserably until 1901, when the Austrian physician, Karl Landsteiner, discovered human blood groups ReynoldsUnwrapped.com offers FANTASTIC, inexpensive daily email subscriptions, where you can receive a HILARIOUS new cartoon every day, and it is a MARVELOUS idea for a UNIQUE gift for your family and friends as well. That is how I learned about this...one of my fellow teachers gave me a subscription as a birthday present. He also has FUNNY greeting cards and BEAUTIFUL paintings for sale as well. You can also get reprints suitable for framing, or originals. Here is more info about his work and a YOUTUBE video. https://nccnews.expressions.syr.edu/?p=11515 66 Microbiology To understand the function of white blood cells, you will need to learn some general concepts and terminology from Microbiology: – Pathogen – General size of bacteria and viruses – Antigen 67 Pathogen “Patho” = disease “gen” = generating A pathogen is something that causes disease. A biological pathogen is a bacterium, virus, fungi, yeast, protozoa, worms, etc. A non-biological pathogen can be a toxic chemical, asbestos, etc. Usually, the term “pathogen” refers to a biological pathogen. 68 Sizes of Pathogens Bacteria are so small that hundreds of them can fit inside one white blood cell. However, bacteria usually do not invade body cells. They live between the cells of the body, using up nutrients in the area, and they cause harm by secreting toxins. Viruses are so small that thousands of them can fit inside the NUCLEUS of one white blood cell, and hundreds can fit inside the “nucleus” area of a bacterium. They always try to invade body cells because they need a piece of our DNA or RNA in order to replicate. When a body cell has been invaded by a virus, the entire host cell must be killed by a white blood cell. 69 Antigen An antigen is anything that causes an immune response, which isn't necessarily a biological pathogen (disease-causing organism). A non-biological antigen can be pollen, dust, grass, or anything that a person is allergic to. Pollen is an antigen to a person with allergies to pollen, but it is not an antigen to a person without allergies to pollen, because no immune response was launched. 70 LEUKOCYTES (White blood cells) all fight infection BASOPHILS – MAST CELL EOSINOPHILS NEUTROPHILS MONOCYTES – MACROPHAGES LYMPHOCYTES – B CELLS – T CELLS too many is ___philia too few is ___penia 71 BASOPHILS Basophils – only about 0.5% of all leukocytes – Granules secrete histamines (vasodilation; more WBCs can get to the infection site) – Antihistamines interfere with the function of basophils. – Mast Cell: a basophil that leaves the blood vessel and enters the tissues. 72 Eosinophils Eosinophils – compose 1-4% of all WBCs – Play roles in: Ending allergic reactions, parasitic infections During these conditions they increase in numbers: eosinophilia 73 74 75 LEUKOCYTES (White blood cells) all fight infection BASOPHILS – MAST CELL EOSINOPHILS NEUTROPHILS MONOCYTES – MACROPHAGES LYMPHOCYTES – B CELLS – T CELLS too many is ___philia too few is ___penia 76 Neutrophils Neutrophils – most numerous WBC First to respond to infection – Phagocytize (eat) bacteria – Also destroy bacterial toxins in body fluids – Nucleus – has two to six lobes 77 White Blood Cell Phagocytosis VIDEO http://www.youtube.com/watch?v=JnlULOjUhSQ 78 Neutrophils Neutrophils are the white blood cells (like the Marine Corp; fast, and first on the scene) that contribute to immunity mainly by engulfing BACTERIA and foreign bodies (thorns, dirt, etc) in a process called phagocytosis. They release the contents of their lysosomes onto the invader, dissolving it. When a bacterium has a capsule, it makes it hard to phagocytize, so the neutrophil requires opsonization by antibodies. 79 Opsonization Some bacteria have evolved a slippery capsule around them as a defense against phagocytosis. The neutrophil cannot engulf this type of bacteria. Neither can a macrophage. When an antibody attaches to this type of bacteria, the neutrophil can now grab onto the antibody like a handle, enabling it to phagocytize the bacteria. This process of facilitation of phagocytosis is called opsonization. 80 When an invading bacteria has the antibody attached to its cell membrane, the entire structure is now called an antigen-antibody complex. If a bacterium does not have a capsule, the neutrophil can destroy it without opsonization. The antibody can also destroy the bacterium by itself by popping the cell membrane like an arrow. But when a capsule is present, the neutrophil and antibody work best together. 81 Monocytes These are like big Army tanks. They Comprise about 5% of all WBC’s. Like neutrophils, they phagocytize (eat) bacteria, old cells, and foreign bodies. They have more types of lysosome enzymes than neutrophils so they are better at killing difficult pathogens. They also use antibodies for opsonization. When they leave the bloodstream and enter the tissues, they are called MACROPHAGES. 82 WBC’s leave the blood vessel to enter the tissues 83 What’s the Difference between Neutrophils and Monocytes/Macrophages? There are 10x more neutrophils in the bloodstream than monocytes/Macrophages. Consider neutrophils to be the most numerous white blood cell. However, there are more macrophages in the tissues of the body. They are everywhere! Neutrophils live only a few days. Monocytes/Macrophages live a few months. Lymphocytes live for years. Monocytes/Macrophages are larger and slower than neutrophils, but they can phagocytize larger organisms and more of them. 84 What’s the Difference between Neutrophils and Monocytes/Macrophages? Neutrophils usually just phagocytize bacteria, eating the whole thing, like a hunter that eats the whole prey. Macrophages phagocytize bacteria but saves a piece of the dead bacterium (like a hunter who saves a trophy) and presents it to a lymphocyte so a larger immune response can occur. 85 Differences in Function There are two types of phagocytes: Neutrophils and macrophages. They kill by eating. – Neutrophils and macrophages both mainly function by phagocytizing bacteria (not viruses). Lymphocytes do not eat what they kill. They leave the dead body behind for the phagocytes to clean up. The lymphocytes are the only ones allowed to kill off body cells infected by viruses. All WBC’s secrete chemicals to recruit more white blood cells to the site. 86 Macrophages present their trophy to T cell lymphocytes and that T cell will present it to a B cell lymphocytes. The B lymphocyte feels the shape of the bacteria pieces, (this is called “antigen presentation”) and then she makes a mold of it. She can then make arrows that fit the shape of that mold. The B lymphocyte can then launch an attack on the rest of that type of bacteria still alive in the body. In this way, the macrophage recruits even more lymphocytes to join the war. So, what is a lymphocyte? 87 Lymphocytes 20–45% of WBCs – The most important cells of the immune system – There are two types of lymphocytes; one makes antibodies and the other engages in direct combat with viruses and can also kill our body cells infected with viruses – Both types of lymphocytes can only act against whatever was presented to them….a specific foreign molecule (antigen) 88 Lymphocytes Two main classes of lymphocyte – – – – B cells – Originate and finish maturing in the bone marrow. When it has not been presented to, it is called a virgin B cell. After presentation, it will mature into plasma cells (warrior Princess). A mature plasma cell fights infection by producing antibodies. After the war is over, the plasma cell will mature into a “queen” , called a Memory B Cell (that will stay pregnant with the antibodies already made so she is ready for the next war). 89 Lymphocytes Two main classes of lymphocyte – – – – T cells – Originate in the bone marrow but move to the thymus gland to mature. They attack foreign cells directly (including organ transplants!). They can also kill viruses by killing the infected host cell. There are 3 different brother T-cells. 90 Lymphocytes B cells – start as virgin cells. Once they have been presented to, they mature into plasma cells (like a warrior princess). Plasma cells secrete antibodies (like arrows fired off into the bloodstream); the plasma cell’s antibodies are what kills the attacking cell. Antibodies attack in three ways: – They attach to bacteria and pop the cell membrane – They attach to encapsulated bacteria to help neutrophils and macrophages to phagocytize them. – They agglutinate (clump all over the bacteria, binding their receptor sites so they cannot cause harm) 91 Disorder of B-cell Lymphocytes Mononucleosis: Epstein Barr virus attacks B lymphocytes. It is characterized by inflammation of lymph vessels (lymphangitis). – Lymphangitis: lymph vessel inflammation; usually from infection. Infected lymphocytes have a characteristic scalloped edge where they touch RBC’s 92 Function of a B Lymphocyte Figure 17.6b 93 T-cell Lymphocytes T cells –can directly destroy bacteria or foreign cells by popping their cell membrane in hand to hand combat. T-cells can also kill a host body cell that has become infected with viruses. They do not phagocytize the invading cell. They just kill the cell and the macrophages dissolve the debris. They do not need the assistance of antibodies. 94 T-Cell 95 T-cell Lymphocytes T cells are the cells that attack organ transplants! Immunosuppression drugs are designed to inhibit the action of T cells. T cells are attacked by the HIV (AIDS) virus. The thymus gland is where the T cells came from. The thymus gland also secrets certain hormones which can cause T cells to become immunocompetent (makes the cells mature and start to work) 96 T Cells There are several types of T cells. The main types are Cytotoxic (Killer) T cells – Go out and directly kill bacteria or infected host cells Helper T cells – Release chemicals called “cytokines” to call in more white blood cells of all types to join in the war. They also present the macrophage’s antigen to a B cell, which causes it to produce antibodies against that particular bacteria. The B cell is now called a plasma cell Suppressor T cells – Stop the immune process when the war is over, and also "tells" some plasma cells to "remember" how to destroy that specific pathogen. Those plasma B-cells are then called Memory B-Cells. They can react to the same pathogen faster, the next time it invades because Memory B-cells already have the proper antibodies stored up for that pathogen. 97 Killer TCell 98 Virus-Infected Cell 99 Function of a T- Lymphocyte Figure 17.6a 100 Summary A pathogen somehow gets past the body's physical and chemical barriers and the inflammation response. The pathogen is engulfed by a phagocyte (macrophage or neutrophil). The macrophage releases the contents of its lysosomes onto the bacterium and dissolves most of it. There are still some pieces of the bacterium’s cell membrane left. The macrophage then forces the surface proteins of the bacterium (antigens) to it's own cell surface. Helper T-Cells touch these surface antigens, make a copy of their shape, and present them to B-cells to make antibodies against them. 101 Summary These Helper T-Cells begin to multiply and have two main roles. The first is to activate B-Cells and "tell" them how to neutralize the pathogen by presenting the pieces of the bacterium cell membrane so the B-cells can turn into plasma cells which make the antibodies. – The B-Cells (now called Plasma cells because they have been activated) begin to multiply and produce the antibodies to neutralize this specific pathogen. The second role of Helper T-Cells is to activate the Killer T-Cells by secreting cytokines. Killer T-Cells can either destroy the pathogen itself (bacteria), or destroy the entire body cell which is infected (viruses). When the immune response is over, Suppressor T-Cells stop the process and also "tell" some B-Cells (plasma cells) to "remember" how to destroy that specific pathogen. Those B-cells (plasma cells) now become Memory B-Cells. 102 Capsule Agglutinates Virus in body cell Pops cell Opsonization Bacteria Antibodies Bacteria Y Plasma Cell Memory B cell Pops the cell Cytokines Phagocytosis STOP Presentation Neutrophil Macrophage (Monocyte in bloodstream) B-Cell Helper T-Cell Killer T-Cell Lymphocytes Suppressor T-Cell 103 How White Blood Cells Work • VIDEO (2 mins) 104 LEUKEMIA Cancer of the blood is called leukemia. It actually only involves the white blood cells since RBCs don’t have a nucleus and cannot reproduce. Something goes wrong in one stem cell, and it starts making huge amounts of clones of itself which don’t work right and not enough normal white blood cells are made. Therefore, the body cannot fight infection. So, the immature white cells are sent into the bloodstream. It’s better to send a young cell with no weapons to the war than to send nothing at all! Think of Leukemia as too few mature white blood cells. Even though the WBC count is high, they are all immature forms. 105 Disorders of WBCs Leukemia – Classified as lymphoblastic (too many immature lymphocytes) or myeloblastic (too many immature neutrophils) 106 Bone Marrow Transplant People with severe leukemia may need a bone marrow transplant. First, all of their WBC’s have to be killed off with a medicine because they are mostly malfunctioning anyway. A donor has a small cylinder of bone removed from their hip. This is ground up and given by i.v. to the recipient. The new WBC’s may kill the patient or it may save their life. It is done as a last resort. 107 UC Riverside student's bone marrow donation saves Iowa man's life Vietor, a 46-year-old Iowa high school basketball coach, was diagnosed with leukemia in 2010. It was a battle he almost lost, had it not been for Fishburn's life-saving bone marrow donation. As it turned out, the 22-year-old University of California at Riverside student was a perfect match. "A year ago, I was probably going to die," Vietor said. "Thanks to him, I have life now and I'm doing great." 108 WBC Count White blood cell (WBC) count is a count of the actual number of white blood cells per volume of blood. Both increases and decreases can be significant. White blood cell differential looks at the types of white blood cells present. There are five different types of white blood cells, each with its own function in protecting us from infection. The differential classifies a person's white blood cells into each type: neutrophils (also known as segs, PMNs, granulocytes, grans), lymphocytes, monocytes, eosinophils, and basophils. 109 Terms Excess neutrophils: neutrophilia Few neutrophils: neutropenia Excess platelets: thrombocytophilia Few platelets: thrombocytopenia 110 Life span, from longest-lived to shortest-lived: Lymphocytes (can live a lifetime) Erythrocytes (live 4 months) Platelets (live about 2 months) Monocytes (live 30 days) Neutrophils (live about a week) 111 Antibodies Antibodies (also known as immunoglobulins, abbreviated Ig) are proteins made by plasma cells. They are typically made of basic structural units—each with two large heavy chains and two small light chains—to form a unit shaped like the letter “Y” 112 A Typical Antibody The tips of the “Y” have receptors that are specific for a particular antigen. The stem of the “Y” can be grasped by a phagocyte. 113 Antibodies The small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen binding sites, to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen. This huge diversity of antibodies allows the immune system to recognize an equally wide diversity of antigens. 114 Antibodies Some of these “Y” shaped units exist by themselves (monomers) Some are in pairs (dimers) Some are in a cluster of five (pentamers) There are five different antibody types , which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter. 115 #1 #2 #3 Precipitation/agglutination 116 Types of Antibodies IgD – initiation of immune response IgE – stimulates allergic reactions, good for worm infections IgG – highest concentration in blood, highest amounts in most secondary responses. Indicates infection was in the past. It can also cross the placenta. IgA – secretory Ig, found in secretions, highest concentration in body IgM – produced first, best at complement (C’) activation. Indicates infection is current 117 IMMUNITY Most people are sick more often as children than as adults in their 20s through 30s because we build up many varieties of memory lymphocytes during childhood, providing immunity from more and more antigens during adulthood. Who is going to be sicker as an adult…the baby of the family or the oldest one? 118 Myasthenia gravis Myasthenia gravis (MG): autoimmune disease where antibodies destroy or block receptors for acetylcholine, a neurotransmitter. Causes flaccid muscle paralysis. First attacks small muscles especially those that keep eyes open; will spread to diaphragm death. To stave off effects, do thymectomy to inhibit the number of T-cells. 119 THROMBOCYTES (platelets) A thrombus is a blood clot. These cells cause blood clots. They are very small compared to all other blood cells. These are pieces of another cell found in the red marrow called a MEGAKARYOCYTE. Pieces break off of a megakaryocte and are known as platelets. When a platelet encounters a broken blood vessel it is like a spider that uses clotting factors (made in the liver and circulating in the blood) to form a web to clot blood. 120 Blood Clot 121 Platelets Cell fragments – Break off from megakaryocytes Function in clotting of blood Platelets Megakaryocyte 122 Platelets Platelets need certain proteins in the plasma called CLOTTING FACTORS (made in the liver) in order for them to become activated and form a clot. The main clotting factor is FIBRIN; it is made from FIBRINOGEN. Vitamin K is needed by the liver to make the blood clotting factors. Thrombocytopenia is too few platelets. 123 Vitamin K Found in green, leafy vegetables. Needed for blood clotting factors. Some types of rat poisons work by eliminating the blood clotting ability. In case of accidental ingestion of rat poison, a child needs an I.V. of vitamin K. It works for accidental poisoning in dogs, too! 124 Aspirin One baby aspirin a day can help prevent blood clots by blocking the action of platelets. It blocks the ability of an enzyme called COX (cyclo-oxidase) to cleave arachidonic acid into a molecule called a prostaglandin. Prostaglandins are needed for inflammatory reactions and for making clotting factors. COX inhibitors, such as aspirin, inhibits pain from inflammation, but they also INCREASE blood clotting time (instead of taking 90 seconds to clot, it might take 3 minutes). 125 Disorders of Platelets – Thrombocytopenia Abnormally low concentration of platelets Blood does not clot properly 126 HEMOPHILIA A hereditary X-linked disease of males, where they are unable to clot properly because they are missing one or more of the 13 clotting factors. When they get even a slight bump or bruise they have to have an intravenous infusion of clotting factors or they will bleed to death. They keep the clotting factor(s) they need in their own refrigerators in their home and give themselves the injection. There are 13 clotting factors, so each type of hemophilia involves a different factor. 127 Blood Clots Thrombus – A blood clot in a vessel Embolism – a thrombus that broke away and travels in the blood stream. – It usually lodges in a smaller blood vessel and blocks circulation distal to that point. 128 Blood Clots Thrombus Embolism 129 Thrombus 130 Thrombus 131 Platelet Count and MPV The platelet count is the number of platelets in a given volume of blood. Both increases (thrombocytophilia) and decreases (thrombocytopenia) can point to abnormal conditions of excess bleeding or clotting. Mean platelet volume (MPV) is a machine-calculated measurement of the average size of the platelets. New platelets are larger, and an increased MPV occurs when increased numbers of platelets are being produced. 132 Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) The PTT test is used to investigate unexplained bleeding or clotting. It may be ordered along with a PT (Prothrombin Time) test to evaluate hemostasis (the process of clot formation). – The PTT evaluates the coagulation factors XII, XI, X, IX, VIII, V, II (prothrombin), and I (fibrinogen). – A PT test evaluates the coagulation factors VII, X, V, II, and I (fibrinogen). By evaluating the results of the two tests together, a doctor can gain clues as to what bleeding or clotting disorder may be present. These tests are used to monitor heparin anticoagulant therapy. Heparin is a drug that is given intravenously (IV) or by injection to prevent and to treat blood clots. IV’s are also flushed with heparin to prevent clot formation. When it is administered for therapeutic purposes, it must be closely monitored. If too much is given, the treated person may bleed excessively; with too little, the treated person may continue to clot. 133 Complete Blood Count (CBC) The complete blood count or CBC test is used as a broad screening test to check for such disorders as anemia, infection, and many other diseases. It is actually a panel of tests that examines different parts of the blood and includes the following: White blood cell (WBC) count White blood cell differential Red blood cell (RBC) count Hemoglobin Hematocrit Mean corpuscular volume (MCV) Mean corpuscular hemoglobin (MCH) Mean corpuscular hemoglobin concentration (MCHC) Red cell distribution width (RDW) platelet count PT, PTT (separate test from CBC) 134 135 Summary of Formed Elements Table 17.1136 (1) Summary of Formed Elements Table 17.1137 (2) Septicemia Septicemia (aka bacteremia or toxemia) is the condition when bacteria invade the body and circulate in the blood. Bacteria can enter the bloodstream as a severe complication of infections (like pneumonia or meningitis), during surgery (especially when involving mucous membranes such as the gastrointestinal tract), or due to catheters and other foreign bodies entering the arteries or veins (including intravenous drug abuse). Bacteremia can have several consequences. The immune response to the bacteria can cause sepsis and septic shock, which has a relatively high mortality rate (kills 1 person in 5). Bacteria can also use the blood to spread to other parts of the body (which is called hematogenous spread), causing infections away from the original site of infection. Examples include endocarditis or osteomyelitis. Treatment is with antibiotics, and prevention with antibiotic prophylaxis can be given in situations where problems are to be expected, such as artificial joint implantation. 138 139 STEM CELLS IN THE RED MARROW STEM CELL: A cell that has not matured and differentiated yet. An embryo has lots of stem cells which have not decided to become a nerve cell, muscle cell, liver cell, etc. Stem cells become the type of cell the body needs. The placenta of a newborn infant has many of these stem cells, too, but not as many as an embryo. That’s why people want to research stem cells on embryos; there are more stem cells there. 140 Stem Cells The first step for a stem cell is to DIFFERENTIATE, which is to decide what system of cells it will belong to (what kind of college to go to….beauty school, trade school, mainstream college). A stem cell that matures in the bone marrow will become a blood cell. Adults don’t have too many stem cells that are so immature that they have not yet decided what system of cells to belong to. Most of our stem cells have matured to the next step, which is that they have decided what system to evolve into (what to major in at college). An adult has stem cells that will ONLY become blood, nerve tissue, organs, etc. 141 Blood Cell Formation Hematopoiesis – process by which blood cells are formed 200 billion new blood cells formed each day The plasma proteins are made in the liver. The blood cells are made in the red bone marrow (spongy bone). 142 Bone Marrow as the Site of Hematopoiesis Red Bone marrow – located within many bones Epiphyses of long bones Girdles (clavicle, scapula, pelvic bones) Axial skeleton (sternum and vertebral bodies) These are the locations for bone marrow biopsies 143 Bone Marrow as the Site of Hematopoiesis Yellow marrow Contains many fat cells Located in the long bones of adults Has nothing to do with forming blood cells. 144 RED BONE MARROW Most blood cells mature in the red bone marrow. When they are almost completely mature, they are released into the bloodstream. When they are old, they are destroyed in the spleen and liver. 145 146 Cell Lines in Blood Cell Formation All blood cells originate in bone marrow. T cells will then move to the thymus gland to mature. All originate from one cell type – blood stem cell. The second step in differentiation is for the blood stem cell to declare its major: – Erythroblasts – give rise to red blood cells – Lymphoblasts – give rise to lymphocytes – Myeloblasts – give rise to all other white blood cells 147 Stages of Differentiation of Red Blood Cells 148 RBC Development ERYTHROBLASTS mature until they are ready to enter the circulation. The nucleus gets pinched off as it enters the blood vessel. When a RBC loses its nucleus, it gains room for more hemoglobin. Some bits of its nucleus are still there for about 2 days, so during this time, they are called RETICULOCYTES. 149 ERYTHROBLASTS These mature into RETICULOCYTES, a RBC with bits of nucleus material, which later dissolves to make room for more Hgb. It is now called an ERYTHROCYTE. 150 LYMPHOBLASTS Give rise to lymphocytes 151 MYELOBLASTS These are the stem cells that mature into the other leukocytes: Neutrophil, macrophage, eosinophil, basophil, platelets. 152 Leukemia Leukemia is cancer of the stem cells. See all these different types of stem cells? That’s about how many types of leukemia there are. 153 Stages of Differentiation of White Blood Cells Figure 154 17.9 IMMUNE SYSTEM INFLAMMATORY REACTION: When you get stuck by a thorn or have an infected cut, the body goes through a series of events called an inflammatory reaction. Four outward signs: – – – – Redness (erythema or rubor) Heat (calor) Swelling (edema or tumor) Pain (dolor) 155 INFLAMMATORY REACTION Redness is caused from the blood vessels dilating to allow more blood flow to the area. Within the blood are platelets to clot the blood, proteins to repair the damage, and macrophages, which are white blood cells that eat up the foreign body, bacteria, or the dead cells. Heat is caused because of the extra amount of warm blood flow to the area. Swelling is caused from the plasma that leaks out of the swollen blood vessels. Pain is caused from the pressure of the extra fluid pressing on nerves in the area. 156 Specific vs. Non-Specific Immunity CELLULAR IMMUNITY Non-specific immune defenses are also call cellmediated immunity, because the monocytes and neutrophils are the main cells involved. Non-specific defenses include inflammatory responses, physical and chemical barriers, and must be primed by the presence of an antigen. HUMORAL IMMUNITY Specific immune defenses are also called humeral immunity, because the main activity is occurring in the blood from the B cells making antibodies. 157 Immunity The immune response is divided into two parts: Innate Immunity (cellular) – The white blood cells doing their job Adaptive Immunity (humoral) – Antibodies 158 ADAPTIVE IMMUNITY Two types of Adaptive Immunity – ACTIVE immunity I have to make my own antibodies Naturally Acquired Artificially Acquired – PASSIVE immunity Someone gives me the antibodies Naturally Acquired Artificially Acquired You can also think of it this way 159 Active Immunity ACTIVE means the person’s own body makes the antibodies. Naturally Acquired – The body is naturally exposed to an infectious agent and launches an immune reaction Artificially Acquired – The person is injected with a weakened (attenuated) or killed organism, as found in a vaccination 160 Naturally Acquired Active Immunity This is when the body is exposed to an infectious agent and the body has to work to produce antibodies which specifically attack that infectious agent. The white blood cells secrete these antibodies which will continue to circulate sometimes for years, ready to attack that type of bacteria and cause them to pop like a balloon before the body can become sick. 161 Naturally Acquired Active Immunity – You catch a cold and eventually get better. You can never get the same cold virus twice because you will have become immune to it. Your next cold is from a different virus. There are hundreds of thousands of cold viruses; that’s why there is no cure for the common cold. – Another example is when an unvaccinated child is exposed to the measles at school and gets the disease, but never gets the disease again. 162 However, there are some diseases that you don’t want to get, even once, such as polio, diphtheria, tetanus, and influenza, because the first exposure could kill or disable you. For these diseases, we have vaccines which are made of those organisms which have been altered (attenuated) so that the body recognizes them as foreign, but they can’t cause disease. That way, if the person is exposed to the real organism later, the antibodies are already there to kill it off without the body getting sick. 163 Artificially Acquired Active Immunity An example is when a child is vaccinated against measles as a baby, so when he gets to school and is exposed to the disease, he doesn’t get sick. 164 Passive Immunity PASSIVE means the person’s body does not have to make the antibodies. Naturally Acquired – Example is the passing of antibodies from mother to infant in breast milk Artificially Acquired – Example is when a person receives an infusion of antibodies from someone else. – Example is the ebola survivor that donates his blood to another infected person. 165 Active vs. Passive Immunity Active immunity is long-lived, and may last for years or even a life time. Passive immunity is short lived, and may last only for a few months. NOTE: A vaccination is not the same as receiving an anti-toxin or anti-venom injection. More on that in Micro class. 166 Vaccine Controversy Fraud http://www.immunize.org/bmj-deer-mmr-wakefield/ http://briandeer.com/mmr-lancet.htm http://en.m.wikipedia.org/wiki/MMR_vaccine_controversy http://www.cnn.com/2011/HEALTH/01/05/autism.vaccines/index.ht ml 167 ALLERGIES From a hypersensitivity to substances such as pollen or animal hair that would not ordinarily cause a reaction. There are two types of allergic responses: Immediate Delayed 168 Immediate allergic response Occurs within seconds of contact with the thing causing the allergy. This is the case with anaphylactic allergies, where someone who is allergic to seafood or peanuts can actually die within minutes because the allergic reaction is so severe the throat swells shut and they can’t breathe. They need an injection immediately of epinephrine that will stop the reaction. 169 170 Delayed allergic response Delayed allergic response is when the body’s first exposure to the substance will not cause a reaction, but all exposures afterward will trigger the response. An example is poison ivy. You won’t itch the first time you touch it. 171 Common allergens 172 173 174 175 Localized anaphylaxis (atopy) reaction limited to the site of allergen exposure pruritis (itchy) and urticaria (hives) allergic rhinitis (hay fever) asthma (atopic asthma) atopic dermatitis (eczema) food allergies 176 AUTOIMMUNE DISEASE A hereditary problem where the body thinks its own tissues are foreign bodies, and it constantly tries to kill off its own tissues. Cats worse than dogs for allergies, http://fxn.ws/O5jueJ VIDEO: How the immune system works 3 mins VIDEO: HIV destroys helper T-cells 3 mins 177 178