Physical Characteristics of Blood

1. Physical Characteristics of Blood • Thicker (more viscous) than water and flows more slowly than water • Temperature of 100.4 degrees F • pH 7.4 (7.35-7.45) • 8 % of total body weight • Blood volume • 5 to 6 liters in average male • 4 to 5 liters in average female • hormonal negative feedback systems maintain constant blood volume and osmotic pressure

2. Hematocrit • Percentage of blood occupied by cells – since RBCs are 99% of these cells, hematocrit is a measurement of RBC count • female normal range • 38 - 46% (average of 42%) • male normal range • 40 - 54% (average of 46%) • testosterone

3. Components of Blood • Hematocrit • 55% plasma • 45% cells • 99% RBCs • < 1% WBCs and platelets

4. 55% plasma: 7 to 8% dissolved substances (sugars, amino acids, lipids & vitamins), ions, dissolved gases, hormones • ions are involved in membrane excitability, determination of fluid pH and osmotic pressure • most of the proteins in plasma are plasma proteins: provide a role in balancing osmotic pressure and water flow between the blood and extracellular fluid/tissues • loss of plasma proteins from blood – decreases osmotic pressure in blood and results in water flow out of blood into tissues – swelling • dispersed as colloid in the blood • do not exit the blood due to their size – creates a protein gradient between blood and interstitial fluid • most common plasma proteins: albumin, globulins, clotting proteins (fibrinogen) • albumins – most abundant • contribute to most of the osmotic colloidal pressure • non-specifically bind many substances to help transport them through the blood • these substances are generally poorly soluble in water • e.g. bilirubin, bile salts, penicillin • globulins – three classes • alpha, beta and gamma • some alpha and beta globulins bind substances for transport • e.g. thyroid hormone, cholesterol • also involved in clotting • many inactive substances are alpha globulins • e.g. angiotensinogen (precursor to angiotensin) • gamma globulins = immunoglobulins • fibrinogen – cleaved by thrombin to produce a very stick mass of fibers made of fibrin • participate in clot formation

5. Blood: Cellular elements • 45% of blood is the cellular elements or formed elements • 99% of this is erythrocytes or RBCs • formed by differentiation of hematopoietic stem cells (HSCs) in the red bone marrow of long bones and pelvis – makes about 2 million per second! • immature RBCs = reticulocytes • still possess a nucleus and organelles • lack mitochondria and cannot use the oxygen they transport for ATP synthesis • maturation of the reticulocyte causes loss of nucleus and organelles and the filling of the RBC with close to 250 million Hb molecules • also contain crucial erythrocytic enzymes • 1. glycolytic enzymes – cells cannot use the O2 they are carrying for energy production • since they lack mitocondria • for energy they rely on glycolysis and the enzymes of this pathway exclusively • 2. carbonic anhydrase – converts the soluble form of CO2 (HCO3 in carbonic acid) into HCO3 at the tissues • most numerous cell type in the body – 4 to 6 million per ul blood • flat, biconcave discs • provides a larger surface area for diffusion of oxygen across their membrane • thinness of the membrane allows rapid diffusion • very flexible membrane that allows their deformation for travel through thin capillaries

6. Erythrocytes: Red Blood cells & their development • hemoglobin • pigment – naturally colored that is red due to its iron content • combines with • oxygen • binding sites • carbon dioxide • the acidic portion of carbonic acid • oxidation of CA occurs at the tissue level • combination of carbon dioxide with water • combination with Hb buffers the pH effects of CA • carbon monoxide • occupies the oxygen binding sites • nitric oxide • binds to Hb in the lungs where it vasodilates pulmonary arterioles to ensure efficient transport of oxygenated blood from the lungs back to the heart • composed of a: • 1. globin portion • four, highly folded protein chains • 2. heme component • four molecules of iron-based heme bound to each globin protein chain • each heme can bind one oxygen – total binding capacity of 4 oxygen molecules per Hb • generally Hb is 98% saturated with oxygen in the capillaries and 60-70% saturated in the tissues at sea level • -saturation level can be affected by temperature (increase temp, decrease saturation) • saturation level can be affected by atmospheric pressure (decrease pressure, decrease saturation) • **acclimatization

7. Erythropoiesis • produced first by the yolk sac • then from myeloid stem cells in the red bone marrow • controlled at the level of the kidneys by the secretion of erythropoietin (EPO) • increased differentiation of the myeloid stem cell • release of mature RBCs or, if needed, the release of reticulocytes • synthetic EPO – can now be made in the lab • used to boost RBC production during chemotherapy, diminishes the need for transfusions • role in blood-doping

8. Feedback Control of RBC Production • Tissue hypoxia (cells not getting enough O2) • high altitude since air has less O2 • anemia • RBC production falls below RBC destruction • circulatory problems • Kidney response to hypoxia • release erythropoietin • speeds up development of proerythroblasts into reticulocytes

9. RBC life-span and recycling • RBC lives only about 120 days – destroyed by the liver and spleen • converts into 700 miles of vessels travelled per RBC before it is destroyed • as it ages the plasma membrane becomes very fragile and prone to rupture • most RBCs are destroyed in the spleen – small vessels tend to lyze the fragile RBCs as they travel through this organ • can also be degraded in the bone marrow and liver by macrophages • 1. liver/spleen/bone marrow degrades the hemoglobin to its globin component and heme • amino acid components of globin are reused for protein synthesis (3) • 2. heme is degraded into free iron and biliverdin – Fe released into the blood • transported in blood attached to transferrin protein (4&5) • stored in liver, muscle or spleen (6) • attached to ferritin or hemosiderin protein • sent to the bone marrow for hemoglobin synthesis (7&8) • 9. biliverdin is converted into bilirubin in the liver (11) which travels to the small intestine in the bile where it is converted into a series of compounds – end up expelled in urine as urobilin (13) or in the feces as stercobilin (14)

10. Polycythemia • too many RBCs (hematocrit over 65%) • dehydration, tissue hypoxia, blood doping in athletes • primary polycthemia • caused by a tumor-like condition of the bone marrow • overproduction of RBCs through increased differentiation of the myeloid stem cell • too many RBCs can increase the viscosity of the blood and result in dramatic decreases in blood pressure as frictional forces in the vessels increase – increases the workload of the heart • increased viscosity also slows the velocity of blood flow - reduce oxygen delivery to tissues • secondary polycthemia • appropriate EPO-induce adaptive mechanism to improve the blood’s oxygen carrying capacity • occurs at high altitudes or in people with chronic lung diseases

11. Anemia • Symptoms • oxygen-carrying capacity of blood is reduced • fatigue, cold intolerance & paleness • lack of O2 for ATP & heat production • Types of anemia • iron-deficiency = lack of absorption or loss of iron • type of nutritional anemia • failure to take in essential raw ingredients not made by the body • pernicious = lack of intrinsic factor for vitamin B12 absorption from the digestive tract • B12 is essential for normal RBC formation and maturation • binding of B12 to intrinsic factor allows its absorption • intrinsic factor – synthesized by the gastric mucosa • hemorrhagic = loss of RBCs due to bleeding (ulcer) • hemolytic = defects in cell membranes cause rupture • rupture of too many RBCs by external factors such as malaria (normal RBCs) or genetic disorders like sickle cell anemia (defective RBCs) • thalassemia = hereditary deficiency of hemoglobin • aplastic = destruction of bone marrow (radiation/toxins) • failure of the bone marrow to produce enough RBCs • may selectively destroy the ability to produce RBCs only • but may also destroy the myeloid stem cells – affect WBCs and platelets

12. Sickle-cell Anemia (SCA) • Genetic defect in hemoglobin molecule (Hb-S) that changes 2 amino acids in the globin protein • at low very O2 levels, RBC becomes deformed by changes in hemoglobin molecule within the RBC • sickle-shaped cells do not pass through capillaries well and get stuck = causing occlusions and decreased blood flow to organs • also rupture easily = causing anemia & clots • Found among populations in malaria belt • Mediterranean Europe, sub-Saharan Africa & Asia • Person with only one sickle cell gene • increased resistance to malaria because RBC membranes leak K+ & lowered levels of K+ kill the parasite infecting the red blood cells

13. Blood disorders • http://members.aol.com/Sheffbp/products/bludphys.htm (Simulation of anemia diagnosis) • http://www.udel.edu/Biology/Wags/histopage/colorpage/ch/ch.htm (Hematopoiesis) • http://www.bloodline.net (Hematology education and news) • http://www.thrombosis.net/lframes/intro.htm (Introduction to thrombosis) • http://www.vh.org/adult/patient/cancercenter/blooddisorders/index.html (Blood disorders) • http://www.bmtnews.org (Blood and Marrow Transplant Information Network) • http://www.psbc.org/hematology (Introduction to hematology) • http://www.pediatrics.emory.edu/ (Sickle cell anemia) • http://www.bloodjournal.org (Journal of the American Society of Hematology) • http://medir.ohsu.edu/cliniweb/C15/C15.378.html (Blood protein disorders)

14. Blood Groups and Blood Types • RBC surfaces are marked by genetically determined glycoproteins & glycolipids • agglutinogens or isoantigens • distinguishes at least 24 different blood groups • ABO, Rh, Lewis, Kell, Kidd and Duffy systems

15. ABO Blood Groups • Based on 2 glycolipid isoantigens called A and B found on the surface of RBCs • display only antigen A -- blood type A • display only antigen B -- blood type B • display both antigens A & B -- blood type AB • display neither antigen -- blood type O • Plasma contains isoantibodies or agglutinins to the A or B antigens not found in your blood • anti-A antibody reacts with antigen A • anti-B antibody reacts with antigen B

16. RH blood groups • Antigen was discovered in blood of Rhesus monkey • People with Rh agglutinogens on RBC surface are Rh+. Normal plasma contains no anti-Rh antibodies • Antibodies develop only in Rh- blood type & only with exposure to the antigen • transfusion of positive blood • during a pregnancy with a positive blood type fetus • Transfusion reaction upon 2nd exposure to the antigen results in hemolysis of the RBCs in the donated blood

17. Hemolytic Disease of Newborn • Rh negative mom and Rh+ fetus will have mixing of blood at birth • Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion • RhoGam binds to loose fetal blood and removes it from body before she reacts • In 2nd child, hemolytic disease of the newborn may develop causing hemolysis of the fetal RBCs

18. Thrombocytes: Platelets & clotting • Disc-shaped, 2 - 4 micron cell fragment with no nucleus • not whole cells! • do have organelles and cytosolic enzymes for generating energy from glucose • Normal platelet count is 150,000-400,000/drop of blood • Other blood cell counts • 5 million red & 5-10,000 white blood cells • Platelets form in bone marrow by following steps: • myeloid stem cells to megakaryocyte-colony forming cells to megakaryoblast to megakaryocytes whose cell fragments form platelets • one megakaryocyte forms 1000 platelets • Short life span (5 to 9 days in bloodstream) • formed in bone marrow • few days in circulating blood • aged ones removed by fixed macrophages in liver and spleen • numbers can be increased through the secretion of thrombopoietin (liver) which increases megakaryocyte development in the bone marrow and stimulates the formation of platelets • 30% of platelets are stored in the spleen – in blood-filled spaces since platelets do not leave the blood

19. Platelet Plug Formation • hemostasis = arrest of bleeding from a broken vessel • 3 steps: • 1) vascular spasm – constriction of smooth muscle layer in damaged vessel • intrinsic response triggered by physical damage – release of paracrine factors from the damaged endothelium • 2) platelet plug formation • 3) blood clotting • Platelets store a lot of chemicals in granules needed for platelet plug formation • platelets do not stick to the smooth endothelium • damage to the endothelial lining exposes collagen fibers to the platelet – results in their activation and adhesion to the collagen fibers to form a plug • alpha granules • clotting factors – initiates the next phase of hemostasis – clot formation • platelet-derived growth factor • cause proliferation of vascular endothelial cells, smooth muscle & fibroblasts to repair damaged vessels • dense granules • ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2 • thromboxane – chemotactic factor for other platelets – platelet aggregation • ADP causes circulating platelets to become sticky – adhere to the first layer of aggregating platelets – results in the secretion of more ADP by the incoming platelets • release of serotonin, epinephrine and thromboxane act as vasoconstrictors to reinforce the initial vascular spasm • aspirin – inhibits COX enzyme which inhibits the production of thromboxane A2

20. Platelet Plug formation • Steps in the process: • (1) platelet adhesion – by collagen interaction • (2) platelet release reaction – from their storage granules • -Platelets activated by adhesion • -Extend projections to make contact with each other • -Release thromboxane A2 & ADP - arrival and activation of other platelets • -Serotonin & thromboxane A2 are also vasoconstrictors decreasing blood flow through the injured vessel • (3) platelet aggregation – self-perpetuating • -inhibited at a specific level by the release of inhibiting factors by the adjacent normal endothelium (prostacyclin and NO) – limits to plug to the area of damage • -actin-myosin interactions contract within the aggregating platelets – strengthens the plug • -plug becomes reinforced through the formation of sticky fibrin strands

21. Blood Clotting • in a test tube gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped • in the body the clot stabilizes the weaker platelet plug and initiates healing • ultimate step is conversion of fibrinogen (soluble plasma protein) into insoluble fibrin • Substances required for clotting are Ca+2, enzymes synthesized by liver cells (clotting factors and plasma proteins) and substances released by platelets or damaged tissues • thrombin – released by damaged cells, catalyzes the conversion of fibrinogen to fibrin • 12 clotting factors involved • Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads • prothrombinase & Ca+2 convert prothrombin into thrombin • thrombin converts fibrinogen into fibrin threads

22. Overview of the Clotting Cascade -may be triggered through two possible paths 1. extrinsic pathway 2. intrinsic pathway -either path leads to activation of the final pathway in which thrombin cleaves fibrinogen to form thrombin

23. Common Pathway • activated prothrombinase and Ca+2 • catalyze the conversion of prothrombin to thrombin • Thrombin • activated factor X (Xa) and thrombin are called serine proteases • in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads • activates fibrin stabilizing factor XIII • stabilizes the forming fibrin mesh • positive feedback effects of thrombin • accelerates formation of prothrombinase • activates platelets to release phospholipids which acts to activate more Factor X and therefore produces more thrombin (positive feedback) • also acts to promote platelet aggregation

24. Extrinsic Pathway • short-cut to clot formation • requires contact with tissue factors produced externally from the blood • damaged tissues produce and release Tissue Factor or thromboplastin into bloodstream • In the presence of Ca+2, clotting factor X becomes activated and combines with clotting factor V to form prothrombinase • Prothrombinase forms in seconds

25. Intrinsic Pathway • drives clotting in damaged vessels and also induces clotting in blood samples in test tubes • all elements for this pathway are present in the blood • Activation of this pathways occurs either when: • endothelium is damaged & platelets come in contact with collagen of blood vessel wall – initiates plug formation by activated platelets • OR platelets themselves become damaged & release phospholipids which activate incoming platelets • Requires several minutes for reaction to occur – occurs concurrently with platelet plug formation and the extrinsic pathway • Substances involved: Ca+2 and clotting factors XII, X and V • first factor – Factor XII (Hageman factor) • activated by contact with exposed collagen or glass surfaces • activated Factor XII requires calcium – which then combines with Factor V to produce prothrombinase

26. 12 Clotting: A summary Platelet aggregation

27. Clot Remodelling • release of the fibrinolytic enzyme plasmin dissolves the clot • plasmin – plasma protein present in the blood as inactive plasminogen • plasminogen becomes trapped in the forming clot, becomes activated to plasmin and slowly dissolves the clot as the tissue repairs itself • white blood cells then phagocytose the remaining parts of the clot as it dissolves • plasmin also functions to prevent clots from forming when not needed • small levels of fibrin are constantly being formed in the blood plasma – yet no clot forms • fibrin is quickly degraded by tissue-type plasminogen activator (tPA) that is secreted by tissues • helps convert plasminogen into plasmin • tPA- along with a similar protease (uPA) - is also released during induced clot formation upon the formation of fibrin – together with factor X, these proteases activate plasminogen • synthetic tPA is now being used as a clot-busting drug to prevent damage to heart muscle by occlusions of coronary arteries • excess levels of activated plasmin circulating freely in the blood are prevented by the formation of plasminogen activator inhibitors (PAIs)

28. Role of Vitamin K in Clotting • Normal clotting requires adequate vitamin K • fat soluble vitamin absorbed if lipids are present • absorption slowed if bile release is insufficient • Required for synthesis of 4 clotting factors by the hepatocytes • factors II (prothrombin), VII, IX and X • Produced by bacteria in large intestine • anti-coagulants called the coumarin drugs (heparin and warfarin) act by competing with vitamin K in the liver • inhibits the formation of the vitamin K-dependent clotting factors

29. Clotting Disorders: Hemophilia • Inherited deficiency of clotting factors • bleeding spontaneously or after minor trauma • subcutaneous & intramuscular hemorrhaging • nosebleeds, blood in urine, articular bleeding & pain • Hemophilia A lacks factor VIII (males only) • most common • over 150 point mutations in the DNA identified • factor VIII acts as a cofactor for the activation of factor X • Hemophilia B lacks factor IX (males only) • less common • over 300 mutations in the DNA identified • Hemophilia C (males & females) • less severe because alternate clotting activators exist • Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor

30. Clotting Disorders • If clotting occurs in an unbroken vessel is called a thrombosis • clots can form in undamaged vessels if the body’s clotting and anti-clotting mechanisms are not kept balanced and in check • inappropriate clot attached to a vessel wall = thrombus • freely floating clot = embolus • thrombosis can result from several factors • 1. roughening of the endothelial lining during arterosclerotic plaque formation • 2. slow moving blood • 3. unbalanced fibrin-plasmin production • 4. widespread release of thromboplastin by tissues • Disseminated Intravascular Clotting : • Life threatening paradoxical presence of blood clotting and bleeding at the same time throughout the whole body • so many clotting factors are removed by widespread clotting that too few remain to permit normal clotting • Associated with infections, hypoxia, low blood flow rates, trauma, hypotension & hemolysis • Clots cause ischemia and necrosis leading to multisystem organ failure

31. Immunity • Immunity: ability of the body to defend itself from infectious agents, foreign cells, cancer cells • immune system has two functional divisions • innate immune system • non-specific immunity • cell-mediated and humoral (secreted) mediated • chemical and physical barriers • chemical: complement and inflammation • no memory • all forms of life • adaptive immune system • pathogen and antigen specific response • cell-mediated and humoral mediated • chemical barriers • memory results • only jawed vertebrates

32. 1) Non-specific defenses: Innate immunity A)Mechanical barriers: first line of defense - Skin and mucus membranes lining the respiratory tract, digestive & reproductive systems e.g. ciliated epithelium of respiratory system - coated with mucus, coughed out B) Chemical barriers (humoral mediated defense): first line of defense -acidic pH of the stomach interior -E.coli within the small intestine -gastric enzymes in gastric juice -high salt in perspiration kills some bacteria C) Fever: second line of defense -secretion of pyrogen by lymphocytes - raises body temp -rise in body temp enhances the phagocytic activity of immune cells D) Inflammation & complement: second line of defense E) Phagocytosis by phagocytic cells (cell-mediated defense) -dendritic cells, macrophages, neutrophils -cells of the innate system: WBCs with the exclusion of the T and B lymphocytes

33. Complement • group of about 20 proteins who control inflammation • several of these proteins are called acute phase proteins (serum proteins that dramatically increase upon infection • e.g. C reactive protein • complement proteins interact with many components of both the innate and adaptive immune systems • similar to a blood clotting system – one complement protein activates another which activated another etc….. • functions • 1. attraction of phagocytes upon activation of the pathway – chemotaxis • 2. coating of foreign cells with complement – recognition of the foreign particle by the incoming phagocytes • 3. intrinsic ability to coat bacteria (opsonization) and lead to their lysis

34. Inflammation: 1) injury to tissue 2) release of histamine and kinins (pain) by damaged cells 3) histamine - dilation of capillaries & increased blood flow -histamine causes the gaps between endothelial cells to widen to allow the passage of larger molecules into the blood – immune cells and complement proteins -however – it can allow for leakage of plasma proteins out into tissues = swelling/edema 4) migration of neutrophils and monocytes/macrophages (WBCs) via capillaries - phagocytosis of foreign particles 5) delivery of proteins to damaged area (e.g. clotting factors) – platelet plug response 6) clotting response by blood - cascade/positive feedback 7) macrophages release Colony stimulating factors - differentiation of more WBCs by the bone marrow and increased distribution systemically 8) production and release of lymphocytes from lymph nodes - travel to infection site -anti-inflammatories (ibuprofen, aspirin, cortisones) can be administered to combact chronic or persistent inflammation -act against chemicals produced by WBCs -anti-histamines - block the binding of histamine to receptors

35. Inflammation • several levels of interaction with the inflammatory system • called the plasma enzyme system • 1. complement – for destruction of microorganisms and induction of histamine release by mast cells • increased vasodilation • 2. clotting system – by production of Factor XII • 3. kinin system – for production of pain, increased vascular permeability and vasodilation • 4. fibrinolytic system – activated by the kinin system • production of activated plasmin • ensured eventual destruction of clot over time • also activated Factor XII

36. WBCs • cells of the lymphoid lineage • T and B lymphocytes • cells of the myeloid lineage • phagocytes and other cells

37. -Leukocytes are 1% of the total cellular elements • - found in the Buffy coat together with the platelets: • -granular and agranular classification • -neutrophils: phagocytic properties • -release lysozymes which destroy/digest bacteria • -release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them • -release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria • - releases cytokines that attract other neutrophils • -eosinophils: parasitic defense cells • -also involved in the allergic response • -release histaminase • slows down inflammation caused by • basophils • -basophils: heparin, histamine & serotonin • -heighten the inflammatory response and account for hypersensitivity (allergic) reaction • -monocytes: enter various tissues and • differentiate into phagocytic macrophages • -lymphocytes: T and B cells Leukocytes: White Blood cells & the Immune system

38. WBC Physiology • Less numerous than RBCs • 5000 to 10,000 cells per drop of blood • 1 WBC for every 700 RBC • Leukocytosis is a high white blood cell count • microbes, strenuous exercise, anesthesia or surgery • Leukopenia is low white blood cell count • radiation, shock or chemotherapy • Only 2% of total WBC population is in circulating blood at any given time • rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen

39. Lymphatic & Immune System Lymphatic system: system of lymphatic vessels and organs -multiple functions 1. defense against disease – lymph flows through lymph nodes -the lymph is filtered by the nodes and microorganisms are destroyed 2. transport of absorbed fat 3. return of filtered proteins – return of plasma proteins that have leaked from capillaries -larger lymphatic vessels are similar to blood vessels - presence of valves -lymphatic vessels - for the transport of lymph -lymph: filtrate produced in tissues and NOT reabsorbed by the CV system -enters lymphatic capillaries from the tissues -low pressure system - moves by muscular contraction and breathing -capillaries join to form lymphatic vessels -vessels join to form: 1) thoracic duct 2) lymphatic duct - Right side head, arm & chest empty into right lymphatic duct and rest of body empties into thoracic duct -then dumped directly into left & right subclavian veins -lymphatic system is ONE WAY (from tissues to heart)

40. Lymphatic organs: 1) lymph nodes: found at certain points along the lymphatic system -capsule surrounding an outer cortex and inner medulla -cortex contains immune cells = lymphocytes (fight pathogens) -medulla contains immune cells = macrophages (clean lymph) 2) tonsils: lymphatic tissue located in the pharynx (adenoids) or oral cavity (palatine tonsils) -defense against pathogens 3) spleen: upper left region of the abdomen -cleanses the blood -capsule, white and red pulp -white pulp contains lymphocytes -red pulp contains red blood cells & macrophages

41. 4) bone marrow (red): adult - within the spongy bone of the epiphyses, pelvis, skull, clavicle, sternum -site of origin for all blood cells (RBCs, WBCs) -derived from hematopoietic stem cells (hematopoiesis) -also the site of origin for all mesodermal cells (bone, muscle, cartilage, fat…..) -derived from mesenchymal stem cells 5) thymus gland: located below the trachea, on top of the heart -divided into lobules -larger in children -production of T lymphocytes -production of hormones - thymosin - stimulates the lymphocytes located in other tissues

42. Cells of Innate and Adaptive Immunity: Neutrophils (Polymorphonuclear Granulocytes) • Polymorphonuclear Granulocytes or Leukocytes • PNGs are about 60 to 70% of circulating WBCs and are also found in extravascular sites • neutrophils are over 90% of the circulating granulocytes • Nuclei = 2 to 5 lobes connected by thin strands • older cells have more lobes • young cells called band cells because of horseshoe shaped nucleus (band) • Fine, pale lilac practically invisible granules • Diameter is 10-12 microns • Fastest response of all WBC to bacteria • Direct actions against bacteria • release lysozymes which destroy/digest bacteria • release defensin proteins that act like antibiotics & poke holes in bacterial cell walls destroying them • release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria

43. Cells of Innate and Adaptive Immunity: Monocyte (Agranulocyte) • also called the mononuclear phagocytic system • two main functions • 1. “professional” phagocytic macrophages – derived from monocytes • 2. antigen-presenting cells • Nucleus is kidney or horse-shoe shaped • Form the reticuloendothelial (RES) system • differentiate into macrophages • Destroy microbes and clean up dead tissue following an infection • fixed group found in specific tissues • alveolar macrophages in lungs • kupffer cells in liver • wandering group gathers at sites of infection • possess numerous lysosomes with acid hydrolases and peroxidase for killing microorganisms • express an Fc receptor on their surface – important for recognizing the foreign microorganism • Diameter is 12 - 20 microns • Cytoplasm is a foamy blue-gray • 3 to 8% of circulating WBCs – form a circulating pool of monocytes • Take longer to get to site of infection, but arrive in larger numbers

44. Cells of Innate and Adaptive Immunity: Phagocytes • one of the first cells to arrive upon inflammation • two kinds: monocytes and polymorphonuclear granulocytes (neutrophils) • attracted through the process of chemotaxis (soluble chemicals that attract cells) • macrophages, neutrophils, dendritic cells • need a method of recognizing the foreign antigen – use antibodies/immunoglobulins • allows non-specific attachment to microorganisms • enhanced if the microorganism has been coated with complement protein – by the C3b protein

45. Cells of Innate and Adaptive Immunity: Eosinophils (Granulocyte) • Nucleus with 2 or 3 lobes connected by a thin strand • Large, uniform-sized granules stain orange-red with acidic dyes • do not obscure the nucleus • Diameter is 10 to 12 microns • 2 to 4% of circulating WBCsLeave capillaries to enter tissue fluid • Release histaminase • slows down inflammation caused by basophils • Attack parasitic worms • Phagocytize antibody-antigen complexes

46. Cells of Innate and Adaptive Immunity: Basophils (Granulocyte) • Large, dark purple, variable-sized granules stain with basic dyes • obscure the nucleus • Irregular, s-shaped, bilobed nuclei • Diameter is 8 to 10 microns • Less than 1% of circulating WBCs • Involved in inflammatory and allergy reactions • Leave capillaries & enter connective tissue as mast cells • Release heparin, histamine & serotonin • heighten the inflammatory response and account for hypersensitivity (allergic) reaction

47. Cells of Adaptive Immunity: Lymphocytes (Agranulocyte) • Dark, oval to round nucleus • Cytoplasm sky blue in color • amount varies from rim of blue to normal amount • Small cells 6 - 9 microns in diameter • Large cells 10 - 14 microns in diameter • increase in number during viral infections • 20 to 25% of circulating WBCs • produced in the primary lymphoid tissues – thymus and adult bone marrow • B cells • destroy bacteria and their toxins • turn into plasma cells that produces antibodies • T cells • attack viruses, fungi, transplanted organs, cancer cells & some bacteria • Natural killer cells = sometimes classified as large granular lymphocytes • attack many different microbes & some tumor cells • destroy foreign invaders by direct attack • kill by binding directly to the target = cytotoxicity

48. Differential WBC Count • Detection of changes in numbers of circulating WBCs (percentages of each type) • indicates infection, poisoning, leukemia, chemotherapy, parasites or allergy reaction • Normal WBC counts • neutrophils 60-70% (up if bacterial infection) • lymphocyte 20-25% (up if viral infection) • monocytes 3 -- 8 % (up if fungal/viral infection) • eosinophil 2 -- 4 % (up if parasite or allergy reaction) • basophil <1% (up if allergy reaction or hypothyroid)

49. Leukemia • Acute leukemia • uncontrolled production of immature leukocytes • crowding out of normal red bone marrow cells by production of immature WBC • prevents production of RBC & platelets • Chronic leukemia • accumulation of mature WBC in bloodstream because they do not die • classified by type of WBC that is predominant---monocytic, lymphocytic.

50. 2) Specific Defenses (Cell-mediated Immunity) Antigens: -before birth, the body takes an “inventory” of all self proteins = antigens -lymphocytes develop receptors that allow them to distinguish between self and foreign -non-self antigens combine with T and B cell receptors and stimulate an immune reaction T Cell-mediated immunity:/Cell-mediated immunity -T = thymus derived -respond to antigens by cell-cell contact - attach to foreign cells directly -antigens are processed before interacting with T cells -antigen-presenting cells (B cells, macrophages)