Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU

Transcription

1 Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU 1 Outline.. I: Functions of the blood The components of the blood Blood clotting Blood groups Diagnostic blood test II: The immune system The immune responses Disorders of the immune system Allergic disease Autoimmunity HIV and immunosuppression Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU 2 Functions of Blood 1. Transport of gases, nutrients and waste products; e.g. oxygen of processed molecules; e.g., precursor of vitamin D from skin to liver then kidneys of regulatory molecules; e.g., hormones 2. Regulation of ph and osmosis (normal ph of most body tissues between 7.35 and 7.45) Maintenance of body temperature; e.g., warm blood shunted to the interior of the body 3. Protection against foreign substances; e.g., antibodies Clot formation 3 1

2 Composition of the Blood -formed elements Red Blood Cells (erythrocytes) White Blood Cells (leukocytes) granulocytes agranulocytes Platelets (thrombocytes) 4 Composition of the Blood -plasma a. fluid: water, ions, hormones b. proteins (most made in liver) 1. Albumin 56% 2. Globulins 38% 3. Fibrinogen 4% Sex hormone-binding globulin Antibody (immunglobulin) 5 Composition of Blood 6 2

3 Production of formed elements Hematopoiesis or hemopoiesis: Process of blood cell production Stem cells: All formed elements derived from single population Proerythroblasts: Develop into red blood cells Myeloblasts: Develop into basophils, neutrophils, eosinophils Lymphoblasts: Develop into lymphocytes Monoblasts: Develop into monocytes Megakaryoblasts: Develop into platelets -blast bud, germ 7 Hematopoiesis Stem cell (hemocytoblast) Proerythroblast Myeloblast Lymphoblast Monoblast Megakaryoblast Early erythroblast Progranulocyte Megakaryocyte Intermediate Basophilic Eosinophilic Neutrophilic erythroblast myelocyte myelocyte myelocyte Late erythroblast Megakaryocyte breakup Nucleus extruded Reticulocyte Basophilic band cell Eosinophilic band cell Neutrophilic band cell Basophil Eosinophil Neutrophil Lymphocyte Monocyte Red blood cell Granulocytes Agranulocytes White blood cells Platelets 8 (RBCs) Red blood cell White blood cell Platelet Components 1/3 2/3 Lipids, ATP, carbonic anhydrase SEM 2600x 7.5 µm 2.0 µm Top view Side view 9 3

4 RBC function: Transport Oxygen from lungs to tissues: 98.5% attached to hemoglobin; 1.5% dissolved in plasma Carbon dioxide from tissues to lungs. 7% dissolved in plasma 23% in combination with hemoglobin 70% transported as bicarbonate ions produced as a result of combination of H 2 O and CO 2 because of enzyme carbonic anhydrase found within RBCs Left shift: increased Hb-O 2 affinity Rhight shift: decreased Hb-O 2 affinity 10 Heme b 2 b 1 CH 3 CH 2 CH 2 COOH Heme CH 2 =CH CH 3 N N Fe N CH 2 CH 2 COOH CH 3 N a 2 a 1 CH 2 =CH CH 3 Types of hemoglobin Embryonic and fetal: have greater attraction for oxygen than adult. Fetal production stops after birth. Adult Oxyhemoglobin: transporting oxygen Dexoyhemoglobin Carbaminohemoglobin: transporting carbon dioxide 11 Erythropoiesis Decreased blood oxygen Increased blood oxygen Kidney Increased red blood cell production Increased erythropoietin Red bone marrow RBCs last 120 days in circulation (enucleated) Production of red blood cells Stem cells proerythroblasts early erythroblasts intermediate erythroblasts late erythroblasts reticulocytes Erythropoietin: hormone stimulates RBC production; produced by kidneys in response to low blood O 2 levels. 12 4

5 breakdown Aged, abnormal, or damaged red blood cells Macrophage Heme Globin Biliverdin 1 2 Iron Bilirubin Amino acids 120 days in general circulation 4 3 Free bilirubin Iron + transferrin Erythropoiesis Liver Storage Spleen Conjugated bilirubin 5 Bile Intestine Kidney Bilirubin derivatives 6 13 breakdown I Macrophage Globin Amino acids Aged, abnormal, or damaged red blood cells 120 days in general circulation Erythropoiesis Liver Spleen Intestine Kidney The globin chains of hemoglobin are broken down to individual amino acids (pink arrow) and are metabolized or used to build new 14 proteins. breakdown II Macrophage Heme Biliverdin Iron Bilirubin Aged, abnormal, or damaged red blood cells 120 days in general circulation Erythropoiesis Liver Spleen Intestine Kidney Iron is released from the heme of hemoglobin. The heme is converted into biliverdin, which is converted into bilirubin. 15 5

6 breakdown III Macrophage Iron Aged, abnormal, or damaged red blood cells 120 days in general circulation Iron + transferrin Erythropoiesis Liver Storage Spleen Intestine Kidney Iron is transported in combination with transferrin in the blood to various tissues for storage or transported to the red bone marrow and used in the production of new hemoglobin (green arrows). 16 breakdown IV Macrophage Aged, abnormal, or damaged red blood cells 120 days in general circulation Free bilirubin Erythropoiesis Liver Spleen Intestine Kidney Free bilirubin (blue arrow) is transported in the blood to the liver. 17 breakdown V Macrophage Aged, abnormal, or damaged red blood cells 120 days in general circulation Erythropoiesis Liver Spleen Conjugated bilirubin Bile Intestine Kidney Most conjugated bilirubin is excreted as part of the bile; some is transported in the blood to the kidneys and excreted in the urine. 18 6

7 breakdown VI Macrophage Aged, abnormal, or damaged red blood cells 120 days in general circulation Erythropoiesis Liver Spleen Intestine Bilirubin derivatives Kidney Bilirubin derivatives contribute to the color of feces or are reabsorbed from the intestine into the blood and excreted from the kidneys in the urine. 19 Normal red blood cells vs. Sickle Cell 20 Sickle Cell Normal mrna Normal protein Mutant mrna Mutant protein GUG CAC CUG ACU CCU GAG GAG AAG val his leu thr pro glu glu lys Mutation (in DNA) GUG CAC CUG ACU CCU GUG GAG AAG val his leu thr pro val glu lys Glutamate (glu), a negatively charged amino acid, is replaced by valine (val), which has no charge. 21 7

8 Sickle Cell Significant change in structure caused by the single mutation Glutamate 6 Valine 6 22 Sickle Cell Anemia Genetic Disease Heterozygous individuals carriers Homozygous individuals diseased SCA Results from Defective s stick together damaged Complications from low oxygen supply to tissues Pain, organ damage, strokes, increased infections, etc. Incidence highest among Africans and Indians Heterozygotes protected from Malaria 23 White Blood Cells Protect body against microorganisms and remove dead cells and debris Movements Ameboid: pseudopods Diapedesis: cells become thin, elongate and move either between or through endothelial cells of capillaries Chemotaxis: attraction to and movement toward foreign materials or damaged cells. Accumulation of dead white cells and bacteria is pus. 24 8

9 Granulocytes Basophils: least common. Leave circulation and migrate through tissues, play a role in both inflammatory response and allergic reactions. Produce histamine and heparin. Eosinophils. Leave circulation and enter tissues during inflammatory response. Prevalent in allergic reactions. Destroy inflammatory chemicals like histamine. Release chemicals that help destroy tapeworms, flukes, pinworms, and hookworms. Neutrophils: after leaving bone marrow, stay in circulation hours then move into other tissues. Become motile, phagocytize bacteria, antigen-antibody complexes and other foreign matter. Secrete lysozyme. Last 1-2 days. 25 Agranulocytes Lymphocytes: produced in red bone marrow but then migrate to lymphatic tissues and proliferate. Responsible for antibody production. Studied extensively with the immune system. Monocytes: remain in circulation for 3 days, leave circulation and become macrophages. Phagocytic cells. Can break down antigens and present them to lymphocytes for recognition. 26 Platelets Cell fragments pinched off from megakaryocytes in red bone marrow Surface glycoproteins and proteins allow adhesion to other molecules; i.e., collagen Important in preventing blood loss Platelet plugs Promoting formation and contraction of clots 27 9

10 Platelets Typical smooth discoid shape of resting platelets Typical spiny spheric shape of activated platelets 28 Outline.. I: Functions of the blood The components of the blood Blood clotting Blood groups Diagnostic blood test II: The immune system The immune responses Disorders of the immune system Allergic disease Autoimmunity HIV and immunosuppression Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU 29 Blood clotting Hemostasis stages: 1) vascular spasm 2) platelet plug formation 3) Coagulation or clot formation Arrest of bleeding Events preventing excessive blood loss The Clotting Process: /folder_structure/tr/m1/s7/trm1s7_3.htm 30 10

11 Platelet plug formation ADP Thromboxane Platelet Granules 1 von Willebrand factor 2 3 Fibrinogen Fibrinogen receptor Endothelial cell Collagen Blood vessel wall Platelet plug Smooth muscle cell 31 Coagulation Stages Activation of prothrombinase Conversion of prothrombin to thrombin Conversion of fibrinogen to fibrin Coagulation factors. Proteins found in plasma. Circulate in inactive state until tissues are injured. Damaged tissues and platelets produce chemicals that begin activation of the factors. Pathways Extrinsic Intrinsic Result: blood clot. A network of threadlike fibrin fibers, trapped blood cells, platelets and fluid

12 Clot formation Extrinsic clotting pathway Tissue damage 1 Intrinsic clotting pathway 2 Contact with collagen of damaged blood vessel Activated factor XII Factor XII Thromboplastin Ca 2+ Factor VII Thromboplastin/ factor VII complex Activated factor XI Factor XI Ca 2+ Activated factor IX Factor IX Stage 1 Activated factor X Factor VIII platelet phospholipids, Ca 2+ Factor X Factor V, platelet phospholipids, Ca 2+ 3 Prothrombinase Stage 2 Prothrombin Thrombin 4 Ca 2+ Activated factor XIII Factor XIII Stage 3 Fibrinogen Fibrin 5 Fibrin clot 34 Extrinsic clotting pathway Begins with chemicals outside of blood Stage 1 Damaged tissues release tissue factor (TF; factor III) When Ca 2+ is present, forms complex with factor VII, activating factor X Prothrombinase is formed Stage 2: prothrombinase converts prothrombin into thrombin Stage 3 Thrombin converts fibrinogen to fibrin Thrombin activates factor XIII, which stabilizes clot 35 Intrinsic clotting pathway Begins with chemicals that are part of the blood Stage 1 In damaged blood vessels, factor XII comes in contact with exposed collagen, activating factor XII Stimulates factor XI, activates factor IX Activated factor IX joins with factor VIII, platelet phospholipids and Ca2+ to activate factor X Prothrombinase is formed Stages 2 and 3 progress to clot formation Stage 2: prothrombinase converts prothrombin into thrombin Stage 3 Thrombin converts fibrinogen to fibrin Thrombin activates factor XIII, which stabilizes clot 36 12

13 Control of clot formation Anticoagulants: prevent coagulation factors from initiating clot formation. Coagulation occurs when coagulation factor concentration exceeds a given threshold. At site of injury, threshold is exceeded. Anticoagulants Antithrombin: produced by liver, slowly inactivates thrombin Heparin: produced by basophils and endothelial cells. Increases effectiveness of antithrombin Prostacyclin: prostaglandin derivate from endothelial cells. Causes vasodilation and inhibits release of coagulating factors from platelets 37 Fibrinolysis Thrombin, factor XII, t-pa, urokinase, lysosomal enzymes 1 Plasminogen Plasmin 2 Fibrin Clot dissolution Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin 38 Outline.. I: Functions of the blood The components of the blood Blood clotting Blood groups Diagnostic blood test II: The immune system The immune responses Disorders of the immune system Allergic disease Autoimmunity HIV and immunosuppression Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU 39 13

14 Blood Grouping Transfusion: transfer of blood or blood components from one individual to another Infusion: introduction of fluid other than blood Determined by antigens (agglutinogens) on surface of RBCs Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs Groups: ABO and Rh 40 ABO Blood Groups Red blood cells Antigen A Antigen B Antigen A and B Neither antigen A nor B Anti-B antibody Anti-A antibody Neither Anti-A nor Anti-B antibodies Anti-A and Anti-B antibodies Plasma Type A Type B Type AB Type O 41 Agglutination reaction + Type A blood of donor Anti-B antibody in type A blood of recipient Antigen and antibody do not match No agglutination + Type A blood of donor Anti-A antibody in type B blood of recipient Antigen and antibody match Agglutination 42 14

15 Transfusion Type A blood has anti-b antibodies Type B blood has anti-a antibodies Suggested that these antibodies are present because of exposure to A and B antigens on bacteria and food Donor: gives blood. Recipient: receives blood Type O as universal donor. Can actually cause transfusion reactions because of antibodies in O blood plasma 43 Rh Blood Group First studied in rhesus monkeys Types Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present 44 Erythroblastosis Fetalis Rh positive fetus, Rh negative mother. Late in pregnancy, Rh antigens of fetus cross placenta (through a tear in placenta or during delivery); mother creates antirh antibodies (primary response) 1 Maternal circulation Maternal Rh-negative red blood cell Fetal Rh-positive red blood cell in the maternal circulation Fetal Rh-positive red blood cell 2 Maternal circulation Maternal Rh-negative red blood cell Anti-Rh antibodies Second Rh positive pregnancy might initiate secondary response and hemolytic disease of the newborn (HDN) 3 4 Maternal circulation Maternal anti-rh antibodies cross the placenta Injection of RhoGAM. Contains antibodies against Rh antigens. Antibodies attach to any fetal RBCs and they are destroyed. Agglutination of fetal Rh-positive red blood cells leads to HDN 45 15

16 Outline.. I: Functions of the blood The components of the blood Blood clotting Blood groups Diagnostic blood test II: The immune system The immune responses Disorders of the immune system Allergic disease Autoimmunity HIV and immunosuppression Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU 46 Diagnostic Blood Tests Type and Crossmatch: determination of ABO and Rh blood types. Red cells tested against antibodies Complete Blood Count Red Blood Count: number of RBCs/ microliter of blood Measurement: grams of hemoglobin/100 ml of blood. For a male, 14-18, female g/100 ml Hematocrit Measurement: percent of blood that is RBCs White Blood Cell Count: 5,000-10,000 /microliter of blood 47 Hematocrit Centrifuge blood in the hematocrit tube 100 Hematocrit tube Hematocrit scale Plasma White blood cells and platelets form the buffy coat 30 Withdraw blood into hematocrit tube Male Female 48 16

17 Differential White Blood Count: determines percentage of each of the five types of WBC Neutrophils: 60-70% Lymphocytes: 20-30% Monocytes: 2-8% Eosinophils: 1-4% Basophils: 0.5-1% Clotting Platelet Count: 250, ,000/microliter Prothrombin Time Measurement: measures how long it takes for blood to start clotting seconds. To test, thromboplastin is added to whole plasma Blood Chemistry: composition of materials dissolved or suspended in the plasma. Used to assess functioning of many body systems 49 Outline.. I: Functions of the blood The components of the blood Blood clotting Blood groups Diagnostic blood test II: The immune system The immune responses Disorders of the immune system Allergic disease Autoimmunity HIV and immunosuppression Blood and Immunity MFEL , Torunn Bruland, IKM, DMF, NTNU