BISC 307L 1st Edition Lecture 29 Current Lecture Blood Hematopoiesis o o This is the red bone marrow that is very prevalent in late fetal life but into adulthood the red bone marrow is restricted to the femur pelvis and ribs o Various levels of commitment of stem cells Pluripotent hematopoietic stem cells give rise to uncommitted stem cells gives rise to a fully committed progenitor cell which is no longer a stem cell o Controlled but hematopoietic cytokines EPO secreted by kidney cells that stimulates production of RBC TPO stimulates development of platelets Variety of interleukins that can stimulate a bunch of cell types o The most abundant blood cell is erythrocytes and they have a lifespan of 90120 days so there is a substantial production of them all the time The cell type that is being produced at the highest rate is neutrophils life span small so produced more often Hemostasis o o Clotting Blood has to flow freely viscosity term The viscosity cant be too high too much resistance The blood should not clot inappropriately But must have ability to clot Process of hemostasis cessation of bleeding 1 Vasoconstriction triggered by the damage of smooth muscle cells This minimizes blood loss When everything is right blood is only in contact with the endothelium except when damaged and it does 2 2 abundant proteins in the layers of the wall collagen and tissue factor The contact of platelets with collagen and tissue factor triggers clotting Tissue factor has several names Coagulation factor 3 thromboplastin Platelets bind to collagen through integrins and make platelets adhere to collagen and make it become sticky and adhere to each other This sticky platelets forms the platelet plug which increases the resistance to blood leaking out and decreases the pressure so flow goes down The stuff oozing out will stop being blood and start being clear serum filtered through the platelet plug Platelets do not aggregate on healthy endothelium because intact endothelial cells secrete nitric oxide which inhibits platelets adhesion and convert membrane lipids into prostacyclin Both inhibit platelet adhesion Platelets secrete platelet factors and the contents of thes are 1 Platelet activating factor PAF o cause synthesis of thromboxane A2 which is a vasoconstrictor 2 Serotonin o vasoconstriction 3 ADP 3 is on next slide 4 Tissue repair self explanatory 5 Thrombolysis removing clot dangerous because if comes loose can go block an artery and cause stroke or heart attack Disassembled molecule by molecule shown on left diagram of next slide Coagulation Cascade o o Step 3 Coagulation cascade Liver makes these clotting factors On right is the extrinsic pathway mechs that are external to the blood Tissue factor 3 Catalyzes conversion of clotting factor 7 into active clotting factor 7 Active clotting factor 7 Makes an active clotting factor 9 Feeds into intrinsic Left is intrinsic involving things in the blood at all times Clotting factor 12 activated buy binding to collagen Catalyzes the conversion of inactive 11 active 11 Catalyzes the conversion of inactive 9 to active 9 which converges on the extrinsic pathway Common pathway 9 when active catalyzes conversion of 10 to active 10 which requires factor 8 as a cofactor and ca2 and membrane phospholipids Active factor 10 converts prothrombin to thrombin Ca2 and clotting factor 5 dependent Thrombin converts fibrinogen to fibrin which is a structural protein and fibrin feeds back and converts inactive 13 active 13 Fibrin monomers will polymerize to form fibers and active 13 cross links fibrin to make cross linked strong mesh This cycle keeps going until something is used up Ca2 is very important Within the fibrin mesh is plasminogen which is an inactive form of the enzyme plasmin which disassembles clots Step 5 The plasmin does this slowly Plasminogen is converted by thrombin or plasminogen activator in tissue tPA to plasmin Active Factor 7 and 10 are important in the repair of the blood vessel This mechanism is very effective in minimizing blood loss and there is promotion of tissue repair built into the clot This is important because it stands between blood loss and clot so it is very regulated Inherited mutations in this include hemophilia which cause excessive bleeding deficit in one or more clotting factors Aspirin useful in treatment of blood clots Inhibits the enzyme that produces throboxane A2 so early on in the clotting method Lymphatic System and Innate Immunity Recall from general biology o o 200 billion erythrocytes day destroyed o 100 billion neutrophils day destroyed Slide 2 Anatomy of lymphatic system o o Lymph capillaries drain into lymph veins which drain into lymph nodes concentrated in armpits and head and neck o Lymph nodes Interstitial fluid is collected by lymph capillaries Very low pressure system pressure gradient created by muscle movement Connective tissue capsule There are physical filters sinuses through which the lymphatic fluid percolates There are lymphocytes and other leukocytes which process sample test and act upon whatever comes through Also a filter system The whole thing is called the lymphatic tissue but some parts are encapsulated lymph nodes spleen Spleen lots of blood flow which percolates through sinuses not completely contained in vessels The blood is very cleaned out after coming out of the spleen The blood going in is dirty but coming out is clean There are two types of tissues 1 Red pulp surrounds sinuses and contains large numbers of macrophages The lining of the sinuses are lined with phagocytes tissue fixed which are like macrophages but don t move 2 White pulp Lymphocytes The liver has a fixed phagocyte called a Kupffer cell There are also called diffuse lymphoid tissues 1 The red bone marrow 2 Gut associated lymphoid tissue GALT loop of small intestine Layer in the wall of the small intestine that is lymphoid tissue and protects the body from very dangerous contents of digestive tract which at the upper end is constantly having contaminated food and liquid passing through In the large intestine there is a lot of bacteria that the body needs to be protected against 3 Tonsils and adenoids defense of upper respiratory tract from infection 4 The thymus gland behind the sternum place where T lymphocytes go to mature born in bone marrow Innate Barrier Defenses o o Review Barriers to outside non specific immune defenses