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USC BISC 307L - Blood and Innate Immunity
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BloodHematopoiesisThis 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 ribsVarious levels of commitment of stem cellsPluripotent hematopoietic stem cellsgive rise to uncommitted stem cellsgives rise to a fully committed progenitor cell which is no longer a stem cellControlled but hematopoietic cytokinesEPO secreted by kidney cells that stimulates production of RBCTPO stimulates development of plateletsVariety of interleukins that can stimulate a bunch of cell typesThe most abundant blood cell is erythrocytes and they have a lifespan of 90-120 days so there is a substantial production of them all the timeHemostasisClottingBlood has to flow freely (viscosity term)The viscosity cant be too high- too much resistanceThe blood should not clot inappropriatelyBut must have ability to clotProcess 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 adhesionPlatelets secrete platelet factors and the contents of thes are :1. Platelet activating factor (PAF)cause synthesis of thromboxane A2 which is a vasoconstrictor2. Serotoninvasoconstriction3. ADP3 is on next slide4. Tissue repair self explanatory5. Thrombolysisremoving 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 CascadeStep 3. Coagulation cascade: Liver makes these clotting factorsOn right is the extrinsic pathway (mechs that are external to the blood)Tissue factor 3Catalyzes conversion of clotting factor 7 into active clotting factor 7Active clotting factor 7Makes an active clotting factor 9Feeds into intrinsicLeft is intrinsic (involving things in the blood at all times)Clotting factor 12 activated buy binding to collagenCatalyzes the conversion of inactive 11 – active 11Catalyzes the conversion of inactive 9 to active 9 which converges on the extrinsic pathwayCommon pathway9 when active catalyzes conversion of 10 to active 10 which requires factor 8 as a cofactor and ca2+ and membrane phospholipidsActive 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 13Fibrin monomers will polymerize to form fibers and active 13 cross-links fibrin to make cross-linked strong meshThis cycle keeps going until something is used up. Ca2+ is very importantWithin 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 plasminActive Factor 7 and 10 are important in the repair of the blood vesselThis 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 regulatedInherited mutations in this include hemophilia which cause excessive bleeding (deficit in one or more clotting factors)Aspirin: useful in treatment of blood clotsInhibits the enzyme that produces throboxane A2 so early on in the clotting methodLymphatic System and Innate ImmunityRecall from general biology200 billion erythrocytes/day destroyed100 billion neutrophils/day destroyedSlide 2-Anatomy of lymphatic systemLymph capillaries drain into lymph veins which drain into lymph nodes (concentrated in armpits and head and neck)Lymph nodesInterstitial fluid is collected by lymph capillariesVery low pressure system, pressure gradient created by muscle movementConnective tissue capsuleThere 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 systemThe 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 tissues1. 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 move2. White pulp: LymphocytesThe liver has a fixed phagocyte called a Kupffer cellThere are also called diffuse lymphoid tissues1. The red bone marrow2. Gut associated lymphoid tissue (GALT)loop of small intestineLayer 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 throughIn the large intestine there is a lot of bacteria that the body needs to be protected against3. Tonsils and adenoidsdefense of upper respiratory tract from infection4. The thymus glandbehind the sternumplace where T lymphocytes go to mature (born in bone marrow)Innate Barrier DefensesReview: Barriers to outside (non specific immune defenses)BISC 307L 1st Edition Lecture 29 Current Lecture Blood- Hematopoiesisoo 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 ribso Various levels of commitment of stem


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