Leukocytes (White Blood Cells (WBC)) and Lymphatic System

Lecture 5 Leukocytes (White blood cells(WBC)) and Lymphatic system Recognize the different structural types of WBCs and their physiological functions. Define the life span and the physiological implication of WBC Differentiate between marginating and circulating pools of WBCs Understand the principle behind the total, relative and absolute WBCs count Understand how to apply this knowledge in clinical practice 1 WBC Types and count Adult human has 7000 WBCs / microL of blood, range (4000-10000) WBCs / microL A. Granulocytes: all have a granular appearance and multiple nuclei (polymorpho-nuclear) 1. Neutrophils: 62.0% (2500-8000 cell) 2. Eosinophil: 2.3% (50-500 cells) 3. Basophils: 0.4% (25-100 cells) B. Agranulocytes 1. Monocytes: 5.3% (100-700 cells) 2. Lymphocytes: 30.0% (1000-4000 cells) • WBC differential count determines the number of each type of WBC present in the blood. • It can be expressed as a percentage (relative numbers of each type of WBC in relationship to the total WBC), or as an absolute value (percentage x total WBC) the absolute value is more important than the relative value 2 Sheet#1 It is to easily distinguish the monocyte during circulation , because it's very large . Also, lymphocyte has a large nucleus, about elohw rieht fo %10 .ezis She said the most thing in this slide, we should focus on the absolute number, not a percentage of WBCs, because when we make a sample or smear of blood ..we would care about the number to detect if there is any infection, but the percentage it will stay the same ..so that's important and we will get more detail later 3 Life Span of White Blood Cells WBC Life span (blood) Life span (tissue) Granulocytes 4 - 8 hours circulating in the blood Few hours during serious tissue infection 4 to 5 days in tissues where they are needed Monocytes they swell to a larger sizes  become tissue macrophages they can live for months unless destroyed while performing phagocytic functions. Tissue macrophages are the basis of the tissue macrophage system, which provides continuing defense against infection 10 - 20 hours in the blood Lymphocytes -They enter the circulatory system continually, along with drainage of lymph from the lymph nodes and other lymphoid tissue. -They re-enter the lymph and return to the blood again and again there is continual circulation of lymphocytes through the body After a few hours, they pass out of the blood back into the tissues by diapedesis. The lymphocytes have life spans of weeks or months, depending on the body’s need for these cells 4 Sheet #2 • There are different types of WBCs, many of them stay in tissue and the others is be in circulation . • About life span, she said during the infection it would decrease because the WBCs would attack the infection and may hydrolysis during that, or damaged by microorganism so that the demand will increase from bone marrow and the number will increase during infection. • About lymphocytes, don't have a specific place .they will transfer between circulation and tissue • Monocyte will differentiate into macrophages and transfers to tissue and there, each tissue or organ that will be inside it,it will have a specific name 5 WBC Physiological functions Neutrophils: • They are the most abundant type of WBC • They engulf and destroy bacteria and pathogens and fight infection A single neutrophil can usually phagocytize 3 to 20 bacteria before the neutrophil becomes inactivated and dies. • They are circulating in blood quickly move to the site of infection or injury to fight infection • They form the first line of defense against bacterial infection because of: 1. High mobility. Neutrophils are capable of amoeboid movement, allowing them to exit blood vessels and reach the site of infection much faster than any other cell. 2. Sensitivity to chemotactic stimuli. Neutrophils respond to chemotactic substances generated by bacteria and injured tissue cells. 3. Phagocytic capacity. Neutrophils form phagocytic vacuoles and are thus capable of ingesting bacteria and any other fragments found at the site of infection 4. Bactericidal activity. They kill phagocytosed bacteria by oxygen-dependent and oxygenindependent enzymatic mechanisms • • • Neutrophils are attracted to inflamed tissue areas by Chemotaxis like: Bacterial or viral toxins, Polypeptides from lymphocytes, mast cells, and basophils. Complement system (C5a). The opsonin protein (Antibody) that coat the bacteria to induce phagocytosis Chemotaxis depends on the concentration gradient of the chemotactic substance: The concentration is greatest near the source (100 μm away from an inflamed tissue) Both neutrophils and macrophages can move through the tissues by ameboid motion with a velocity of 40 μm/min 6 Sheet # 3 • .We main in amoeboid movement that the nutrophile will change from there place and shap to cross the endothelial vessels • amoeboid movement : (pseudopodia)an act of changing physical location or position or of having this changed (from Google ) • The process of attracting the nutrophiles by chemotaxis is dependent on the distance, the far to react should be less than 100 micro-m, 7 Phagocytosis of bacteria (1) The bacterium acts chemotactically, attracting the neutrophil (2) Adherence of bacteria to the surface of leukocytes is facilitated by Opsonins (Opsonization: the binding of the antibody IgG and the complement fragments (C3) to microbes to make them susceptible to phagocytosis) (3) The bacterium is engulfed in the pseudopodia formed (4) Phagocytosis of the bacterium includes formation of a phagosome from the phagocytic vacuoles and lysosomes. (5) Phagocytosed bacteria are killed by oxygendependent and oxygen-independent mechanisms (6) Killed bacteria are digested (7) During the interaction with the bacterium the neutrophil may be killed, releasing its cytoplasmic contents into the extracellular space (pus) 8 Sheet # 4 • Now to make sure understanding what the happens ,read this review from last semesters: • Complement System : The complement system is a collection of soluble proteins and their membrane receptors that function mainly in host defense against microbes and pathologic inflammatory reactions . • There are more than 20 complement proteins, some of which are numbered C1 through C htob ni noitcnuf yehT .9innate and adaptive immunity for defense against microbial pathogens. • Upon activation, different complement proteins : • )1(coat (opsonize rof seborcim sa hcus ,selcitrap (phagocytosis & destruction , Just for reading • )2(increased vascular permeability dna , 9 • )3(induce WBC chemotaxis Sheet # 5 • When antigen attacks the body, complement system will assist in response by the immune system will produce antibody (also called immunoglobin, and has many types ) and it binds in antigen (may microorganism ) and form complex, and here comes role the complantry system, C1 will bind in this complex to form C3 type and coating them, to recognize on antigen by macrophages and killing it. • all that to recalling & understanding, don't save anything of them. What the doctors said about this slide : The neutrophile is the first line of defining against the infection . Phagocytes will contribute in kill bacteria The lysosome contains killing enzymes to infection & their PH is very low so that they must be found inside the vacuole 10 Pools of WBCs • Within blood vessels there are two pools of WBC (Neutrophils): 1) Circulating pool: Circulating cells are free flowing in blood 2) Marginating pool: Cells are temporarily adhered to endothelial cells (vessel wall) by selectins (cell surface lectins mediate the adhesion of WBC to endothelial cells and platelets under flow) • Reaction of Neutrophils to infection: The neutrophils become marginated (adhered)  then activated (secrete biologically active substances that act on endothelial cells, macrophages, and lymphocytes) respond to chemotactic stimuli  migrate toward the bacteria in the tissue. • Cytokines and other biologically active substances produced at the site of inflammation act on the bone marrow, causing a release of neutrophils into the circulation (neutrophilia) and increased production of neutrophils in the bone marrow. 11 Eosinophils • About 2 % of all the blood WBC • They have a short half-life (18 hours) in the circulation, they enter the tissues by diapedesis (90% of eosinophils are found in tissues) • They are abundant in the mucosa of the gastrointestinal, respiratory, and urinary tracts. • Their maturation and activation is stimulated by IL-3, IL-5, and GMCSF • They are weak phagocytes • They release proteins, cytokines, and chemokines that produce inflammation • They are produced in large numbers in people with: (1) Parasitic infections They attach themselves to the parasites by surface molecules and release substances (hydrolytic enzymes, reactive forms of oxygen, larvicidal polypeptide) that kill the parasites like; schistosomiasis, trichinosis that causes eosinophilia (2) Allergic reactions: as in the lungs in people with asthma and in the skin after allergic skin reactions The mast cells and basophils release an eosinophil chemotactic factor that causes eosinophils to migrate toward the inflamed allergic tissue The eosinophils detoxify the inflammation-inducing substances released by the mast cells and basophils and phagocytize and destroy allergen-antibody complexes  thus preventing excess spread of the local inflammatory process. 12 Sheet#6 • About the end article, she said this process (bring the eosinophil to the site of allergy ) is considered an example of positive feedback, • Positive feedback : is a process in which the end products of an action cause more of that action to occur in a feedback ) elgooG morf( 13 Basophils • The basophils resemble large tissue mast cells located outside capillaries in the body. • Both mast cells and basophils liberate 1. Heparin into the blood (a substance that can prevent blood coagulation) 2. Histamine 3. Bradykinin and serotonin • They play a role in allergic reactions they bind to immunoglobulin E (IgE) that is produced in response of allergic reactions. Mechanism of action 1) IgE molecules bind to high-affinity receptors on the surface of mast cells and basophils 2) The subsequent cross-linking of these molecules with the allergen cause the cells to releases (histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis and a number of lysosomal enzymes) 3)Causing bronchoconstriction, lung inflammation and airway hyperresponsiveness observed in asthma and allergic reactions. 14 Lymphocytes • A lymphocyte is a type of white blood cell that is part of the immune system • It differentiates into: 1. The B cells produce antibodies that are used to attack invading bacteria, viruses, and toxins. 2. The T cells plays a role in the adaptive immune response and produce cytokines. 3. Natural killer (NK) cells are giant lymphocytes of the innate immune system that control several types of tumors and microbial infections • Only 2% of the lymphocytes are in the peripheral blood, the rest are in the lymphoid organs • After birth, some lymphocytes are formed in the bone marrow, but most are formed in the lymph nodes, thymus, and spleen from precursor cells that originally came from the bone marrow. After residence in the thymus or liver, many of the T and B lymphocytes migrate to the lymph nodes. • Lymphocytes enter the bloodstream via the lymphatics. 15 Sheet#6 • She said the lymphocytes are produced from bone marrow, but most of them will differentiate in lymphoid organs according to our reference. 16 Monocytes • They are made in the bone marrow and travels through the blood to tissues in the body where it becomes a macrophage or a dendritic cell. • They respond quickly to inflammation signals and the site of infection  phagocytose and kill microorganisms • They can ingest foreign material, remove dead cells, and boost immune responses. • They act as antigen-presenting cells: participate in antigen uptake and presentation to lymphocytes • They produce cytokines and chemokines in response to infection and injury • They participate in tissue repair, as in wound and fracture healing • Macrophages can engulf large particles, even whole RBCs or malarial parasites, they can survive and function for months. 17 Monocyte-Macrophage system (the reticuloendothelial system) • Macrophages that present in the tissue are attached • They break away from their attachments and become mobile in response to chemotaxis as result of inflammation • The 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 • Macrophages present in the body organs that are susceptible for infection like: 1) Skin and subcutaneous (fight infections resulted from broken skin) 2) Lungs (present at the alveolar walls to phagocytize pathogens entrapped into the alveoli) 3) Gastrointestinal tract (bacteria from ingested food pass through the gastrointestinal mucosa into the portal blood. Before this blood enters the general circulation, it passes through the Macrophages (Kupffer Cells) in the Liver Sinusoids. • If the pathogens are not destroyed in the tissues, they enter the lymph and flow to the lymph nodes, where they get trapped in a meshwork of sinuses lined by large number of macrophages. 18 Sheet#8 • As we said before the monocyte goes to the tissue, it will differentiate into specific types of macrophage in each organ • This macrophage will be inside the tissue of organs adherent and mobile (adherent find it, to kill microbes during circulation and mobile to kill microbe during the tissue. • There are macrophages in the subcutaneus layer that consider the first line to kill any microbe try to cross the skin if cut happens, and a lot of them in the lung because the air that we hellanting fill in pathogens .also in live to filtrate the blood that comes from GIT before diffusing them on the body 19 Genesis of WBC (Leukopoiesis) • The myelocytic lineage: start with the myeloblast  form four different types of WBC Basophil, Neutrophil, Eosinophil and monocyte • The lymphocytic lineage: start with the lymphoblast  differentiated into B and T lymphocytes • The granulocytes and monocytes are formed only in the bone marrow  They are stored until they are needed in the circulatory system • Lymphocytes are produced in the lymph glands, spleen, thymus, tonsils. • The production of granulocytes is rapidly increased in infections SCF= Stem cell factor; Tpo = Thrombppoietin; IL= Interleukin; GM-CSF= Granulocytes Macrophages Colony stimulating factor. Epo = Erythropoietin; MCSF= Macrophages Colony stimulating factor G-CSF= Granulocytes Colony stimulating factor; SDF-1= Stromal cell derived factor-1 ; FLT-3 ligand= 20 FMS-like tyrosine kinase 3 ligand; TNF-a = Tumor Necrosis Factor alpha, TGFβ = Tumor Necrosis Factor beta Sheet#9 • Don't memorise all interleukins, just we should know they are the reason for producing the specific type of RBC, for example in Lymphocytes if was exposed to the cascade of interleukin it will get Tlymphocyte if not, it will get the B-type. • She said focus ii-3 and GM-CSF, they found in many ways 21 WBC disorders • Lymphoma: a blood cancer that occurs in the body's lymphatic system. • Leukemia: a blood cancer in which malignant WBC multiply inside your body's bone marrow • Myelodysplastic syndrome (MDS): a condition affecting the WBC in bone marrow  The body produces too many immature cells, called blasts The blasts multiply and crowd out the mature and healthy cells It sometimes leads to leukemia. 22 Lymphatic system • A subsystem of the circulatory system in the vertebrate body that consists of a complex network of vessels, tissues, and organs (Tonsils, thymus, spleen, lymph nodes, bone marrow) • It helps maintain fluid balance in the body by collecting excess fluid and particulate matter from tissues and depositing them in the bloodstream. • Functions of the Lymphatic System 1. Transports excess interstitial fluid (lymph) from tissues to the veins 2. Produces and houses lymphocytes for the immune response 3. Transports absorbed fats from intestines to blood Subsystem : it is mean helper system that will reabsorb to extrafluid and retained again to circulation 23 Relation between circulatory and lymphatic systems • The lymphatic system supports the circulatory system by draining excess fluids and proteins from tissues back into the bloodstream, thereby preventing tissue swelling. Lymph flow Lymphatic capillaries Pulmonary capillary network Lymph node Lymphatic vessels Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interstitial space Lymph capillary Tissue cells Capillary bed Lymph node Blood flow Systemic capillary network Venule Lymph duct Arteriole Lymphatic capillaries 24 Spleen Functions; 1. Act as a blood filter: it recognizes and removes old, malformed, or damaged RBC. 2. Phagocytosis: Old and abnormal erythrocytes are destroyed in the spleen, the breakdown products (hemoglobin, bilirubin and iron) are transported to the liver 3. Storage of blood: The spleen contains up to 350 ml of blood, and in response to sympathetic stimulation can rapidly return most of this volume to the circulation, e.g. in hemorrhage. 4. Immune response: The spleen contains T- and B-lymphocytes, which are activated by the presence of antigens, e.g. in Lymphocyte proliferation during serious infect cause enlargement of the spleen (splenomegaly). 5. Erythropoiesis: The spleen and liver are important sites of fetal blood cell production. 25 Tonsils: - Part of the body's immune system. Because of their location at the throat and palate, they can stop germs entering the body through the mouth or the nose. - They contain a lot of WBC, which are responsible for killing germs. Thymus: - An important part of the body's immune system, it helps to fight infection. - It makes T lymphocytes. The thymus produces all our T cells before we become teenagers. It gradually becomes less active and eventually gets smaller and is replaced by fat tissue. - It also produces a hormone called thymosin that helps make and develop T cells. Lymph nodes: - They are small, oval-shaped organs that contain immune cells to attack and kill foreign invaders, such as viruses. - They are found in various parts of the body, including the neck, armpits, and groin. • They are major sites of lymphocytes that include B and T cells. • Acting as filters for foreign particles including cancer cells. 26