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functions of blood?
•Transport and Distributing vehicle:
•nutrients and oxygen to cells
•metabolic wastes away from cells
•hormones and regulatory factors to and from cells
•humoral agents and cells of immune system
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•Maintenance of homeostasis:
•acting as a buffer
•maintains osmotic balance
•thermoregulation
•Storage and transport of clotting factors (coagulation)
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megakaryocytes break up into? and through what mech?
platelet demarcation channels
membrane invagination
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what is hemostasis?
control of bleeding
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4 zones of thrombocytes?
1) peripheral (cell membrane and glycocaylx): GAGs, glycoproteints, coagulation factors
2) structural (microtubules and actin) supports plasma membrane
3) organelle zone - center of platelet, has granules
4) membrane zone
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what are the 3 types of granules in thrombocytes?
alpha - fibrinogen, plasminogen, plasminogen activator/inhibitor, platelet derived growth factor (intitial phase of repair)
delta- ADP/ATP, serotonin (vasoconstriction), histamine - platelet adhesion
gamma - similar to lysosomes, hydrolytic enzymes (clot resporption)
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Steps to Vessel Repair?
- 1) primary aggregation - platelets exposed to collagen or air, collagen binding protein
- 2) secondary aggregation - alpha and delta granules released (glycoproteins and ADP increase size of clot) serotonin (vasoconstriction)
- 3) blood coagulation (cascade of 13 plasma proteins --> leads to fibrin --> formation of clot/thrombus
- 4) clot retraction
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what happens in clot retraction?
clot moves away so that blood can flow in vessel again
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clot removal?
plasminogen (inactive form) is activated by plasminogen activator and turns into plasmin (lyses up the clot)
gamma granules
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2 stems of hematopoeisis?
1) myeloid stem cell -- everything
2) lymphoid stem cell - lymphocyte
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list of granulocytes
- neutrophils
- eosinophils
- basophils
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Mast cells
- store chemicals
- mediators that activate inflammatory process
- permanent residents of connective tissue (not blood cells!)
- released when the immune system needs to be stimulated
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what is anaphylaxis
gnarly allergic reaction
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what do mast cells secrete?
- histamine (slow-reacting
- substance of anaphylaxis SRS-A)
-eosinophil chemotactic factor
-neutrophil chemotactic factor
-heparin
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plasma cells
release antibodies that bind to Fc receptor on mast cells
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first exposure?
second exposure?
1st time: exposed to pollen, b cell binds pollen, turns into plasma cell and secretes a bunch of pollen antibodies, these antibodies (IgE) attach themselves to mast cells
2nd time: the IgE primed mast cells release granules and powerful chemical mediators into the environment (cause typical symptoms of allergy)
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monocytes
- migrate to CT
- neutrophils do kamakazi missions, then monocyts come in - differentiate into macrophages - display antigen presenting cells in MHC (major histocompatibility complex)
- they are like commanders/ provide intelligence
- have a horseshoe nucleus
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whats up with monocytes' nuclei?
- horseshoe nuclei
- indented b/c huge golgi apparatus
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what causes monocytes to differentiate into macrophages?
- presence of necrotic material
- invading microorganisms
- inflammation
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what do monocytes phagocytose?
- cell and tissue debris
- remaining bacteria
- dead neutrophils
- neoplastic cells
- abnormal extracellular material
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different monocytes. where are these?
1) kupffer cell
2) alveolar, pleural and peritoneal
3) microglia
4) langerhans cell
5) osteoclasts
6) antigen presenting cells of lymphoid organs
- 1) liver
- 2) body cavities
- 3) brain
- 4) epidermis
- 5) bone
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macrophages
1) how are they activated?
2) what happens when activated?
- 1) lymphokines released by lymphocytes
- and exposure to immune complexes
- 2) release of neutral proteases and GAGases (facilitate migration)
- release other compounds involved in anaphylaxis and inflammatino
- main antigen presenting cells (After digestion disply antigengs of foreign "invader" on surface in form of major histocompatibility comples II
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histamine and heparan sulfate
cause dilation of small blood vessels
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eosinophils
- kill protozoans and worms
- bilobed nucleus
- stimulated by mast cell releases
- have granules
- involved in allergic reactions, chronic inflammation, and parasitic infections
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basophils
- the least numerous
- similar to mast cells
- receptors for IgE
- stimulate B cells
- granules: heparin, histamine, SRS
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what type of allergy will have a lot of basophils?
derm, baby
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what is the only WBC that returns from the tissue back to the blood? and what is this called?
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lymphocytes are immunocompetent which means what?
they are already primed to bind to only one kind of antigen
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how are basophils and mast cells similar?
- they have the same function - they are both stimulated by exposure to an antigen
- and they both respond by: binding to the antibody (IgE) secreted by he plasma cell and releasing granules
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what is an immunocompetent cell?
which cell type is this often?
a cell that has developed the capacity to recognize adn respond to antigens and are in transit from one lymphatic tissue to another
- lymphocytes!
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lymphocytes
what are the 3 types? and characteristics of each?
- in blood, most common agranulocyte
- T cell - recognizes antigens bound to MHC
- B cell - produces antibodies
- NK - kill certain virus-infected cells and some types of tumor cells
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how many liters in body?
5-6 (7-8% of body weight)
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2 components of blood and what is inside them?
- 1) cells and cell fragments (46% by volume)
- erythrocytes (RBC))
- leukocytes (WBC)
- platelets (thrombocytes)
2) plasma: liquid ECM of blood
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what is serum?
ECM without clotting factors
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hematocrit?
amoutn of volume packed erythrocytes/unit volume of blood, greater in men
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what is in plasma?
- electrolytes
- nutrients
- dissolved gases
- vitamins
- hormones
- lipoproteins
- wastes
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3 main plasma proteins:
- 1) albumins
- 2) globulins (alpha, beta, gamma)
- 3) fibrinogen (also prothrombin)
also lipoproteins
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albumin
- main plasma protein
- made in the liver
- smallest protein
- important for osmotic pressure (needs to stay in capillary, if it leaks out then osmotic pressure decreases so you get edema :(, also important for regulation of exchange of materials between plasma and EC fluid
- carrier protein - binds and transports insoluble substances (bilirubin ex)
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globulins
- immunoglobulins
- gamma, largest component, secreted by plasma cells, antibodies
- nonimmune globulins:alpha and beta, secreted by liver, maintain osmotic pressure, , carrier protein (copper, iron)
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fibrinogen
- made in liver
- in a cascade of rxns with other coagulation factors, polymerizes to form the insoluble protein FIBRIN (forms clot)
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4 different staining characteristics of blood:
basophilia (deep blue) : dna, rna, granules of basophils
azurophilia (purple): lysosomes, granule found in leukocytes
eosinophilia (pink): hemoglobin, granules of eosinophils
neutrophilia (salmon pink/lilac): cytoplasmic granules of neutrophils leukocytes
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what is a reticulocyte?
immature red blood cell (no nucleus)
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erythrocytes
- a nucleate
- no orgnalles
- bind oxygen to deliver to tissues
- bind CO2 to remove from tissues
- biconcave disc gives it greater SA
- extremely flexible
- stain pink (eosin)
- live 120 days
- fit perfectly into capillart
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structure of hemoglobin
- 2 alpha chains
- 2 beta chains
- heme group with iron
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reticulocytes
- immature red blood cells
- normally about 1% of RBC
- important number to check - will increase due to a bunch of things (high altitude, internal clotting, anemia)
- compressed RNA
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anemia
- blood concentration of hemoglobin is low
- can be caused by lots of stuff
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sickle cell anemia
- single pt mutation in beta globin chain of hemoglobin
- under low oxygen conditions, aggregate into sicle shape
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leukocytes
- divided into granulocytes and agranulocytes
- granulocytes = mature diferentiated ones, only last a few days at most, not actively dividing, cleaned up by macrophages
mainly found in connective tissue, ones in blood are in transit!
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granules that are in all leukocytes
nonspecific azurophilic (purple) granules = lysosomes!
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neutrophils
- INFANTRY MEN! short lived :(
- energy source is glycolytic pathway to make ATP
- most common type of leukocyte
- phagocytosis!
- multilobed nucleus
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3 types of granules in neutrophils:
- 1) specific: granulocyte, very small, barely visible
- - bacteriostatic and bactericidal agents
2) azurophilic granules: lysosomes (larger and less numerous)
3) tertiary granules: more enzymes
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mechanism that neutrophils enter connective tissue
PHASE 1: macrophages and mast cells already in infected CT, recognize infection- secrete cytokines - causes endothelial cells to express selectin receptor (selectin is on neutrophil membrane) - neutrophil rolllls along endothelial cell (rolling adhesion) slows n. down.
PHASE 2: cytokins cause endothelial cells to secrete chemokines - activate integrins on surface of neutrophil (tight adhesion).
cytoskeleton of neutrophil reorganizes, flattens on endothelial cells, extend pseudopod
transmigration: epithelial cells held together. mast cells secrete heparin and histamine that loosen junctions and allow nutrophil pseudopod to find a way through to the CT. mast cells release proteases to degrade ECM so neutrophil has room to move
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chemotaxis
once neutrophil is in the CT it migrates further towards site of injury
lasts 1-2 days
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diapedesis
outward passage of white blood cells through intact vessel walls
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neutrophils do phagocytosis from recognition of receptors:
1) Fc receptors - binds to antibodies (phagocytosis)
2) complement receptors (chemical warfare)
3) toll -like receptors (recognize common pathogenic molecules)
4) scavenger receptors (recognize certain lipoproteins found on bacteria)
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phagosome
antigen when it has been engulfed inside the neutrophil
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mechanism of phagocytosis
neutrophil takes in antigen - phagosome
glucose is taken into the cell, goes through pentose phosphate pathway (shunt) instead of glycolysis, then makes NADPH and H, NADPH is taken up by NDPH oxidase on surface of phagosome, it adds the high energy electrons and adds them to oxygen making a superoxide O2-, either combines with H+ to make peroxide or singlet O2 (both damaging to bacteria)
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big pic of phagocytosis:
RESPIRATORY BURST! take all neutrophil's energy stores to create killing environment, shove high energy electrons into lysosome to make all damaging products
- left with dead bacteria in cytoplasm
- dead bacteria +dead neutrophils = pus!
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why do you get a fever sometimes when you have an infection?
- neutrophils secrete interleukins (pyrogen - fever inducing agent), which induces prostaglandins, which activate hypothalamus to produce fever
- -want to activate hypothalamus for extra help
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big picture of inflammatory response!
- endothelial cells of blood vessel suck neutrophils into CT, neutrophils have various receptors, neutrophils phagocytosis bacteria and die, monoctyes come into CT and clean up all the crap (turn into macrophages) and display MHC
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what produces immunoglobulins?`
plasma cells
alpha and beta
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what produces nonimmunoglobulins?
the liver
(gamma)
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immunoglobuilins are .../?
antibodies!
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