HTHS Mod 15

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  1. What is blood
    • one component of cardio system (along w heart and vessels)
    • Considered a connective tissue because:
    • it has cells - WBC, RBC, platelets
    • and an extracellular matrix - plasma
    • *to be considered connective tissue: has cells & matrix (ground substance= plasma)& has fibers
    • *the fibers aren't in the blood UNTIL the clotting mechanism is activated, then the proteins for clotting become fibers
  2. Functions of the blood
    • Very important part of maintaining homeostasis
    • Transportation: oxygen, carbon dioxide, hormones and nutrients
    • Regulation: body temp and pH
    • Protection: resistance to diseases
  3. Physical characteristics of blood
    • Viscosity
    • Temp - (100.4°)
    • pH
    • Color - variable shades of red depending on O2
    • Volume - 4-6 L depending on person (gender and body mass)
  4. Explain Viscosity of blood
    it's thicker than water due to solutes, colloids, and suspended formed elements
  5. Two main components of the blood
    • 45% - Cells, or more specifically formed elements = WBC, RBC, platelets
    • 55% - Plasma - typically clear, yellow liquid

    *called formed elements cause of platelets: they aren't cells, they are fragments of cells
  6. what exactly are platelets?
    • they are actually the remnants of cells
    • *we have great big cells in bone marrow (megakaryocytes) which are too big to leave bone marrow. Therefore, when they implode and the cytoplasm breaks apart, it's the  cytoplasm fragments that become the platelets
    • Thats why they are classified as formed elements
  7. What is the breakdown of plasma
    • 92% water, 8% solutes
    • * 7 of the 8% are plasma proteins. The other 1% are misc solutes
  8. What are Plasma Proteins
    • Many types that have individual functions, frequently as carrier molecules
    • Collectively they contribute to osmotic balance
    • Majority produced by hepatocytes, so liver problems can lead to plasma protein problems
  9. What are the names of the plasma proteins and what's the % breakdown
    • 54% albumins
    • 38% globulins - named from "globe" like appearance
    • 7% fibrinogen (clotting protein)
    • 1% misc solutes: electrolytes, nutrients, gases, hormones, and waste products
  10. gamma globulins
    • important type of globulins
    • also called immunoglobulins or antibodies
    • produced in response to organic molecules the body see's a foreign
    • Serve as flags for immune system, so it knows what needs to be destroyed

  11. How many of each formed element are in the blood
    • Platelets = 150-400 K
    • WBC = 5 - 10 K
    • RBC = 4.8 - 5.4 million
    • *PER CUBIC millimeter (μL = microliter- is same thing)
  12. -poieisis
  13. hematopoiesis
    • general term for the development of the 3 types of formed elements of the blood:
    • Leuko-poiesis = making WBC
    • Erythro - poiesis = making RBC
    • Thrombo - poiesis = making platelets (thrombo- meaning clots, so platelets make clots)
  14. where does hematopoiesis take place and what's it made from
    • happens in red bone marrow
    • Formed from pluripotent stem cells and mature as either a myeloid or lymphoid stem cell, which is decided under the influence of various cytokines
  15. pluripotent stem cells & red bone marrow
    • "pluri-" = many; "potent" = potential
    • what all blood cells begin as, in the red bone marrow
    • can be influenced by body to become any of the mature blood cells
    • *In infants, all bones contain red bone marrow & are actively making formed elements. As person matured, red bone marrow in long bones is replace w yellow bone marrow (mostly adipose tissue)
  16. What are cytokines
    • chemical signals from one cell that influences another
    • act as small protein hormones to control cell growth and differentiation
    • proliferation and maturation of blood cells depends on specific cytokines ~ cells differentiate into either myeloid group or lymphoid group
  17. What specific cytokines are there?
    • EPO
    • TPO
    • Interleukins
    • Interferon
    • TNF
    • CSF
  18. EPO
    • erythropoietin ~ type of cytokines
    • increases # of early red blood cells in the bone marrow
  19. TPO
    • Thrombopoietin ~ specific type of cytokines
    • increases the formation of platelets
  20. CSF
    • type of cytokines
    • colony-stimulating factors
    • increases production
  21. Interleukins
    • Cytokines btwn white blood cells
    • *"inter" - "leukins"
  22. Interferon
    • Cytokines which have anti-viral properties and stimulators of the immune system
    • **Ferron battling viruses
  23. TNF
    • Tumor-necrosis factor
    • type of cytokines
    • Produced by macrophages to encourage inflammation
    • **Think of the tumor as a zit...After you eat a big Mac,  You're going to squeeze the hell out of the zit cause its got inflammation n ready to pop
  24. Myeloid group
    The group in which the immature myeloid (bone marrow) cells differentiate and become red blood cells, platelets, and many types of white blood cells
  25. lymphoid group
    • The group in which immature lymphoid cells mature in the lymphatic system 
    • give rise to a specific group of white blood cells called lymphocytes
  26. Describe the structure of mature RBC's
    • Are bi-concave discs (like donut but middle doesn't go all the way through) - gives high surface to volume ration
    • Demonstrate reversible-deformity - able to squeeze through small spaces (capillaries) and snap back into shape
    • Live 120 days
    • *the bi-concave shape results through the loss of it's nucleus
  27. What happens as a RBC matures... how do they survive?
    • Loses it's nucleus and organelles - this provides max cytoplasmic space to carry O2
    • hemoglobin increases
    • decreased cellular size
    • *cause they lack mitochondria, they don't use any of the oxygen they carry. They utilize glycolysis to stay alive
  28. Describe the function of RBC
    • Carry oxygen
    • If damaged, they are removed from circulation by phagocytic white blood cells, the spleen, and the liver
  29. hemoglobin
    • the oxygen & CO2  carrying molecule of red blood cell
    • Makes blood red
    • approx 280 million in each RBC
    • Each consist of 2 main components: heme and globin
    • each hemoglobin has 4 globin and 4 hemes
    • Therefore, one red cell can carry 1.1 billion oxygen atoms
  30. globin
    • a protein comprised in hemoglobin
    • made up of 4 polypeptide chains; two alpha chains and two beta chains
    • Each polypeptide chain has a heme molecule bound to it
  31. heme
    • a ringed molecule with one iron (Fe2+) atom at the center
    • Is the binding site for oxygen on hemoglobin
    • Each Fe2+ can pick up one oxygen molecule at the lungs
  32. hemoglobin at the lungs vs at the tissue level
    • In the lungs, has a high affinity for oxygen; wants to pick it up and hold it
    • At tissue level, has lower affinity for oxygen; so it wants to let go. That's when it can pick up CO2 to transport it to lungs for exhale
  33. Erythropoiesis
    • part of hematopoiesis, specifically production and maturation of RBC
    • produced continuously
  34. -emia
    • means "in the blood"
    • or emic
  35. How is the rate of erythropoiesis measured?
    • by a reticulocyte (retic) count
    • measured as they are coming out of the bone marrow
  36. hypoxemia
    • results when the number of red blood cells lost exceeds the number made
    • Therefore, too little oxygen in the blood
    • *this lack of oxygen isn't from breathing problems, there just isn't enough red cells to transport the available oxygen around the body
    • The decreased amount of oxygen stimulates the kidneys to secrete EPO
  37. EPO
    • erythropoietin = cytokine
    • a hormone secreted by the kidneys when oxygen levels in blood become low
    • circulates to red marrow and speeds up maturation and release of immature red cells
  38. reticulocyte
    • an almost mature RBC
    • still contains some mitochondria, ribosomes, and endoplasmic reticulum
    • released into blood stream and will mature over next 1-2 days
    • Normally, 0.5 - 1.5% of circulating red blood cells are reticulocytes
  39. Hct
    • hematocrit
    • the % of a pt's whole blood that is occupied by red blood cells
    • average is 45%, with men being a little higher and women being a little lower
  40. Polycythemia
    • the presence of too many red blood cells
    • can manifest as a primary or secondary disease
    • Increases the blood viscosity
  41. Polycythemia vera
    • also called primary polycythemia
    • an abnormality of the bone marrow causing overproduction of red blood cells
    • may also result in increase of white cells and platelets (so increase in formed elements)
    • Biggest problem is it increases the viscosity of blood which can make the heart work harder and increase likelihood of clotting
  42. Secondary polycythemia
    • an increase in red cell numbers due to another condition
    • *any stimulus that causes hypoxemia can cause the bone marrow to increase the production of red cells
    • Ex: smoking, sleep apnea, prolonged exposure to low atmospheric oxygen, or heart disease
  43. relative polycythemia
    • type of secondary polycythemia which involves dehydration
    • **When I go visit my "RELATIVE" in AZ I get dehydrated
  44. Anemia
    • an insufficient amount of RBC's or hemoglobin
    • most common cause is iron deficiency
    • 2 ways to classify: Etiology or Appearance
  45. etiology of anemia
    • etiology = the cause of the disease
    • Ex: hemorrhagic, iron deficiency, etc
  46. classifying RBC by Appearance includes:
    • Size: Macrocytic, normocytic, and microcytic
    • Hemoglobin (color) content: Hypochromic and normochromic
    • *"-chromic" = color
  47. Hemorrhagic anemia
    • Size of RBC: Normocytic
    • Amt. of Hemoglobin: Normochromic
    • Cause: Bleeding
  48. Iron deficiency anemia
    • Size of RBC: Microcytic
    • Amt of Hemoglobin: Hypochromic
    • Cause: lack of iron
    • **Small ironing board and small iron...
  49. Pernicious anemia
    • Size of RBC: Macrocytic
    • Amt of hemoglobin: Normochromic
    • Cause: Vitamin B12 deficiency
    • **Imagine turning the P in Pernicious into a B, as in Bern... but linking to Burns at Rockin R. He was a big guy, but normal in color
  50. Hemolytic anemia
    • Size of RBC: normocytic
    • Amt of Hemoglobin: Normochromic
    • Cause: destruction of RBC's
  51. Aplastic anemia
    • Size of RBC: Normocytic
    • Amt of Hemoglobin: Normochromic
    • Cause: bone marrow failure
  52. Leukocyte
    • a white blood cell
    • Larger then red cells
    • Have nuclei
    • Don't have hemoglobin
    • normal WBC count is 5.0 - 10.0 x 103
    • Two groups, divided by presence of cytoplasmic granules:
    • Granulocytes and Agranulocytes
    • *the granules are visible under microscope when stained
  53. granulocytes
    • also called granular leukocytes
    • 3 specific groups:
    • Neutrophils
    • Eosinophils
    • Basophils
    • *names come from staining characteristics
  54. Neutrophil
    • type of granulocyte
    • Makes up 60-70% of total WBC's in blood stream
    • Function: Powerful phagocyte, increased in bacterial infections and inflammation
    • In an eosin stain, stains somewhere btwn red and dark purple
    • Self destructs after attack, in pus
    • *Think of "Neut" protecting me much of the time, fighting bacteria bad guys
  55. Eosinophil
    • Type of granulocyte
    • Makes up 2-4% of total WBC's in blood stream
    • Function: Allergic reactions, parasitic infections
    • *full of histamine 
    • Has large red granules when stained
    • **Remember allergies are "sin"-ful, E stains red like Erythro = red blood cells
  56. Basophil
    • Type of granulocyte
    • makes up .5-1% of total WBC's in blood stream
    • Function: is poorly understood, chronic inflammation
    • has traces of anticoagulant and histamine
    • Has large dark blue granules (when stained)
    • **B = Blue
  57. agranulocytes
    • one of 2 types of WBC
    • do contain some cytoplasmic granules, but they are much less prominent and don't stain as well as their granulocytic counterparts
    • Include Lymphocytes and Monocytes
  58. Lymphocytes
    • type of agranular leukocytes
    • Makes up 20-25% of total WBC's in bloodstream
    • provide long term immunity
    • Function: Major role in viral infections and cancer prevention
    • include T Lymphocytes, B lymphocytes, and NK (Natural killer) cells
  59. Monocytes
    • type of agranular leukocytes
    • makes up 3-8% of total WBC's in bloodstream
    • Function: differentiate into macrophages (phagocyte), present in chronic inflammation and infections
    • Enlarge and mature into macrophages in various tissues of the body
    • Have various names depending on where it's at
    • Comes into play if infection sticks around longer after neutrophils attack
  60. Leukocytosis
    • an increase in the number of white blood cells
    • WBC count is greater than 10.0 x 103 WBC/mm3
    • Is a normal physiologic response, up to a point - any disruptions in homeostasis can cause increase in WBC
    • Common causes are bacterial infections, viruses, parasites, stress, temp extremes, etc.
  61. Leukemia
    cancer of blood-forming cells, most often white cells
  62. Leukopenia
    • a decrease in white cell numbers
    • WBC count is less than 5.0 x 103   WBC/mm3
    • Never a normal response
    • There isn't a normal physiological reason for a persons WBC count to go down
    • Causes include: AIDS, chemotherapy, bone marrow failure (aplastic anemia)
    • **Think of small "penis" ( -penia )
  63. WBC differential analysis
    • way to figure out the percentage of each type of WBC in the blood
    • provides info relating to pt condition
  64. WBC differential
    • Physicians use % of WBC in blood to aid in diagnosis of specific diseases
    • WBC work together to provide a powerful immune response, but each type has unique role:
    • Increased granulocytes in bacterial infections
    • Increased lymphocytes in viral infections
  65. thrombocytes
    • also called platelets
    • cytoplasmic fragments of megakaryocytes
    • 2-5 k platelets develop from one megakaryocyte
    • very active in clot formation by:
    • forming plug
    • releasing chemicals to encourage vasoconstriction and activate coagulation
    • *live 5-9 days
  66. megakaryocytes
    large cells in the bone marrow which are too big to leave, so they emplode and form blood platelets
  67. platelet plug
    formed by platelets to help limit blood loss
  68. hemostasis
    • the overall process by which bleeding is stopped
    • Three mechanisms:
    • Vascular spasm
    • Platelet plug formation
    • coagulation
  69. Vascular spasm
    • the constriction of damaged blood vessels
    • One of 3 mechanisms involved with hemostasis
    • limits the amount of blood lost
    • due to chemicals released from platelets, damage to the smooth muscle, and pain receptor reflexes
    • *Only vessels with smooth muscle can do this, capillaries can't
  70. Platelet plug formation
    • Platelets are very active in hemostatic process - like little bags of procoagulant chemicals
    • Three step process:
    • 1st ~ platelets adhere to wall of blood vessel
    • 2nd ~ platelets release their chemical contents (which encourages further vasoconstriction and recruitment of other platelets) 
    • 3rd ~ due to chemical release, the newly activated platelets become sticky (platelet aggregation)
    • W activation of enough platelets, a loose platelet plug is formed
  71. platelet aggregation
    the clumping of platelets during hemostasis
  72. coagulation
    • taking plasma and making a clot
    • Series of complex enzymatic reactions designed to activate specific coagulation proteins; most are plasma proteins
    • Activated in step-wise/cascading fashion (such as knocking down domino's... said domino's referred to as clotting or coagulation factors)
    • The coagulation proteins are enumerated with Roman numerals
    • Most clotting factors synthesized by liver
  73. Clotting pathway activation
    • Two separate pathways to activate coagulation, which merge to form a common pathway:  (could consider it as 3 pathways)
    • Extrinsic pathway
    • intrinsic pathway
    • *each pathway activated in a slightly different fashion, name gives hint to their activator
    • *typically activated at same time
  74. Extrinsic pathway
    • One of two clotting pathway activation's
    • activated by damage outside of vessel, specifically tissue
    • TF is released from damaged tissue into the blood
    • Has fewer steps and occurs rapidly
  75. TF
    • tissue factor
    • also called tissue thromboplastin
    • A tissue protein (is a fluid) released from damaged tissue, used to activate clotting
    • involved in extrinsic pathway for clotting
    • activation
    • *Tips over the first domino for extrinsic (if begins w intrinsic injury)
  76. intrinsic pathway
    • one of two clotting pathway activation's
    • activated by damage to vessels
    • Exposed vascular collagen, damaged endothelium, or activated platelets are all potent coagulation activators
  77. Stages of coagulation
    • Merge at the common pathway
    • Activate the enzyme prothrombinase
    • Prothrobinase acts on prothrombin (factor II) to become thrombin
    • Newly formed thrombin activates fibrinogen (factor I) to become fibrin
    • *Fibrin proteins are threads that form the clot and strengthen the platelet plug
  78. exogenous vs. endogenous
    • exogenous is outside of body cells
    • endogenous is inside body cells
  79. What cofactors must be present for clotting factor synthesis and coagulation to occur?
    • Vitamin K - in the synthesis of clotting factors 2, 7, 9, 10
    • Calcium - required for almost every step of coagulation process
    • *therefore, a person deficient in these would have a hard time clotting
  80. Plasma vs Serum
    • Plasma is the liquid portion of unclotted blood, where the clotting process is inhibited and clotting factors remain inactive and soluble
    • *Still have "domino's" within the blood so it will clot
    • Serum is the liquid portion of clotted blood, which forms a clot by activating the soluble clotting factors
    • *The "domino's" have already been tipped over. Can't clot
  81. Thrombus
    a clot that is stationary
  82. embolus
    • a circulating particle, often a clot that may obstruct a blood vessel
    • Can be fat, air, cholesterol plaque, blood, clump of platelets, etc.
  83. thromboembolus
    a stationary clot that dislodged from it's primary site and traveled to another location
  84. fibrinolysis
    clot dissolution
  85. fibrinolytic system
    • the "un-clotting" system
    • As coagulation occurs, substances from both tissue and blood activate the enzyme plasminogen to become plasmin
  86. plasmin
    • a very potent proteolytic enzyme (proteolytic enzyme meaning digesting/breaking down protein)
    • dissolves the clot:
    • fibrinolysis (digesting fibrin)
    • interferes w new clot formation by inactivating fibrinogen, prothrombin, and other clotting factors
  87. anticoagulants
    • Although they are commonly referred to as "blood thinners", they do not thin the blood
    • it interferes w the coagulation process
    • are a # of different ones; some used for therapeutic reasons and others for specimen collection
    • common goal is to inhibit coagulation process
  88. Heparin
    • Anticoagulant
    • Administered intravenously to a stroke or heart attack victim
    • also used in surgery and dialysis
    • Discourages the common pathway: Inactivates thrombin and factor X
  89. Warfarin
    • Also called Coumadin
    • Anticoagulant
    • Oral medication used to inhibit clotting in high-risk pts
    • Interferes w the synthesis of a # of clotting proteins; most importantly the synthesis of Vitamin K
    • *Also used for pesticide, specifically rodenticide. (D-con mice poison = mouse anticoagulant)
  90. EDTA
    • Anticoagulant
    • Present in blood-draw tubes used for blood counts
  91. Sodium Citrate
    • Anticoagulant
    • Present in blood collection bags for blood donations
  92. Aspirin
    • Anticoagulant
    • Inhibits platelet aggregation
  93. Thrombolytics
    • chemicals used in medicine that breakdown clots that have already formed
    • Used for strokes, heart attack, emboli and thrombi
  94. TPA
    • tissue-plasminogen activator
    • Drugs that are given to stroke/heart attack victims when they come into the hospital
    • Gets rid of the clots they have ; activates the thrombinogen to become plasmin
    • Therefore, activates the fibrinolytic system
  95. Two major blood groups
    ABO and Rh systems
  96. Blood type determined by the presence or absence of A and B antigens (markers) on surface of red cell (A, B, both A and B, or the total lack of A and B)
    The A and B antigens are genetically determined: A genes codes for A antigen, B gen codes for B antigen, O gene results in lack of either A or B
  97. ABO blood = which is dominant, which is recessive?
    • Both A and B are dominant
    • O is recessive
    • Therefore, if a person doesn't inherit an A or B, they will lack the antigens and have O blood type
  98. Explain the antibodies a person with have in their plasma to the A or B antigens they lack
    • A antigens on red cells, Will have B antibodies in the plasma
    • B antigens on red cells, will have A antibodies in the plasma
    • AB antigens on red cells, no A and B antibodies in the plasma
    • No A or B antigens on the red cells, A and B antibodies in the plasma
    • *The antigens are present at birth, but the antibodies are not. They are formed shortly after birth (within 6 months)
  99. Rh blood type
    • identifies whether a person has the Rh antigen or not
    • So simply just another marker on the cell
    • If they have it, they are Rh+, if they don't they are Rh-
    • 85% of population has it
    • *people do not normally have antibodies to the Rh antigen, but they can develop it if they are ever exposed to Rh+ blood (cause they don't have the antigen, it is foreign)
  100. blood transfusions
    • you know what this is
    • just remember, a whole blood transfusion is rare. 
    • Just parts of the blood are given, such as red blood cells
  101. Universal donor
    • blood type O
    • doesn't have any A or B antigen on the red blood cells, therefore there isn't anything for the immune system to see
  102. universal recipient
    • blood type AB
    • doesn't have any A or B antibodies in their plasma
    • their system already knows what A and B antigens look like, so they aren't foreign
  103. What happens with a transfusion reaction?
    • If pt receives wrong blood type, their antibodies to the corresponding antigens will cause the incorrect RBC's to be destroyed by the immune system
    • This can cause pt to develop a fever, go into shock, or result in acute renal failure
  104. HDN
    • Hemolytic disease of the newborn
    • caused by blood incompatibility btwn a fetus and mother
    • Most serious cause is Rh incompatibility
    • Problem arises if:
    • -Dad is Rh+
    • -Mom is Rh-
    • -Baby is Rh+ , due to genetics inherited from father
    • *but note that mom and baby are incompatible. If mother is exposed to baby's blood (in childbirth, trauma, etc) mom develops antibodies against Rh. This can be a problem if she becomes prego again. 
    • *Her antibody can cross placenta and target fetus' red cells

  105. What happens when Mom's Rh antibodies are attacking baby's Rh+ red cells
    • It starts attacking Baby's red blood cells in the uterus
    • Baby becomes anemic because of a loss of red blood cells; not getting enough oxygen
    • To compensate, baby's heart starts pumping faster, trying to circulate the red cells it has left
  106. How is Rh incompatibility dealt with?
    • The mothers who are Rh- are given an injection (in late middle pregnancy and at delivery)  of Rhogam (IF baby is Rh+)
    • Rhogam is a commercially produced Rh antibody
    • *"Rh-" = Rh   "-gam" = gamma globulin
  107. How does Rhogam work?
    • helps get rid of the Rh+ cells from baby before the mother's immune system sees them.
    • Does this by flagging any Rh+ cells to be destroyed BEFORE HER immune system sees them.  
    • So the Rh+ are flagged to be destroyed by the shot
    • In this way, she never develops the ability to make Rh- antibodies ON HER OWN.
  108. What if mother is Rh+ and baby is Rh- ?
    • Its not a problem
    • Baby is neg. So there isn't an Rh antigen to see
    • Mom is Rh+, already has Rh antigen
    • immune system doesn't make antibody to antigen it doesn't recognize as foreign
  109. lymphatic system
    • System consisting of lymphatic vessels through which lymph passes
    • Functions:
    • Draining interstitial fluid
    • Transporting dietary lipids absorbed by the gastrointestinal tract to the blood
    • Facilitating immune responses
  110. What is included in the lymphatic system?
    • Lymphatic fluid
    • Lymphatic capillaries
    • Lymphatic vessels
    • Lymph nodes
    • Lymphatic trunks
    • Lymphatic ducts
    • red bone marrow
    • thymus
    • spleen
  111. Lymphatic capillaries
    • what lymph vessels begin as
    • located throughout body in interstitial spaces
    • have overlapping endothelium that allows interstitial fluid in, not out
    • held in place by anchoring filaments (specialized fibers arising from capillaries and extending into tissue)
    • As they converge, they form larger lyphatic vessels
  112. Lymphatic vessels
    • vessels which carry lymphatic fluid (lymph) one way, from the tissue back into the blood stream
    • have thin walls and valves to encourage one-way fluid movements
  113. Lymph nodes
    • bean-shaped lymphatic organ surrounded by connective tissue capsule
    • serve as a filter for lymph fluid
    • Foreign objects are trapped and destroyed
    • Approx 600 in body, present at intervals along the lymphatic vessels
    • provide opportunity for lymph to come into contact w immune system
    • like a specializing sampling process
    • *Lymph enters through the afferent vessels, exits through the efferent vessels[
  114. Thoracic duct
    • The left lymphatic duct
    • where all lymph from Left upper body and entire lower body
    • Located at meeting point btwn left internal jugular vein and left subclavian vein
  115. Right lymphatic duct
    • only drains the right upper body & extremity
    • Also drains into blood stream at junction of Right internal jugular vein and right subclavian vein
  116. interstitial fluid
    • formed by plasma that is filtered by the capillary walls
    • clear fluid
    • less protein than plasma
    • Most is reabsorbed back into the blood through venous end of capillary
  117. plasma
    • liquid component of blood
    • filtered through capillary walls to form interstitial fluid
    • Large proteins don't pass through the capillaries
    • *still has clotting proteins
  118. Lymphatic fluid
    • Unaltered interstitial fluid in the lymphatic vessels (that fluid that is not reabsorbed)
    • Absorbed dietary lipids
    • essentially, just drainage from the tissue, so it is identical to interstitial fluid
  119. Lymphatic flow is moved by:
    • Pressure in interstitial space
    • Skeletal muscle contraction: "milks" lymphatic vessels and encourages movement
    • Respiratory movements: encourage lymph flow by increasing and decreasing thoracic and abdominal pressures
    • *In both scenarios, valves present in lymphatic vessels restrict black-flow of lymph
  120. What is the flow of lymphatic fluid (where does it flow)
    • 1. Plasma in the blood vessels
    • 2. Interstitial fluid
    • 3. Lymphatic capillaries
    • 4. Lymphatic vessels
    • 5. Lymphatic ducts
    • 6. Back into the blood stream
  121. Primary lymphatic organs/tissues
    • Locations where stem cells divide to produce immune cells
    • Bone marrow and thymus
  122. Secondary Lymphatic organs/tissues
    • Locations of cell maturation and immune responses
    • Includes lymph nodes, spleen, lymphoid tissue (tonsils, MALT)
  123. immunocompetent
    • happens as a cell matures
    • means they can facilitate an immune response
  124. Thymus
    • located in mediastinum btwn sternum and aorta
    • in infants, is approx 70 grams, with age shrinks to only 3 grams, but still continues to release some mature T cells
  125. Bone marrow
    • one of the primary lymphatic organs
    • stem cells here divide to produce both B lymphocytes and T lymphocytes
  126. B lymphocytes
    • begin as stem cells in the bone marrow
    • Will remain in bone marrow to mature
    • activated to become plasma cells WHICH the job of plasma cells is to make antibodies
  127. T lymphocytes
    • begin as stem cells in the bone marrow
    • Will leave as pre-T lymphocytes and migrate to the thymus gland to become immunocompetent
  128. Lymph nodes vs lymph nodules
    • lymph nodes have a connective tissue capsule
    • Lymphatic nodules do not have a capsule
  129. lymph nodules
    are considered secondary lymphatic tissue

    Ex: Peyer's patches in the intestinal tract, portions of the appendix, and the tonsils (pharyngeal, adenoid and palatine)
  130. spleen
    • stores blood and helps with blood supply
    • helps get rid of dead red blood cells
    • sits in left upper quadrant
    • One of most common things injured in trauma; making it easy to bleed to death
    • Full of immune cells
  131. What regions in the body are lymph nodes grouped together more prominently
    • Cervical
    • Submandibular
    • axillary
    • inguinal
  132. trabeculae
    extensions of the lymph node capsule which divide the node into compartments
  133. two regions of a lymph node
    the cortex and the medulla
  134. Flow of lymph through lymph node
    • lymph flows into node via afferent lymphatic vessel
    • flows through cortex, where it sees lots of B lymphocytes, dendritic cells, and macrophages
    • continues to flow through node into medulla
    • there it is exposed to more B lymphocytes, plasma cells (activated B cells) and more macrophages
    • lymph then exits through efferent vessels
  135. Innate immunity
    • consists of a # of different cellular and chemical barriers
    • Non-specific
    • Non-adaptive - meaning it doesn't change from exposure to exposure
    • Has two lines of defense
  136. Components of Innate immunity
    • skin
    • mucous membranes
    • cilia
    • endogenous antimicrobials
    • inflammation
    • phagocytosis
    • fever
  137. Adaptive immunity
    • Provides the ability to respond against specific invaders 
    • Is specific & adaptive
    • Generates memory
    • *sometimes considered 3rd line of defense
  138. Innate Immunity: First line of defense
    • skin
    • mucous membranes
    • lacrimation
    • salivation
    • flow of urine
    • vaginal secretions
    • defecation
    • vomiting
    • Each of these barriers protects the various external opening of the body
  139. Innate Immunity: Second line of defense
    • Comprised of the internal defenses:
    • Endogenous antimicrobials
    • Complement system
    • Iron-binding proteins
    • Interferon (chemical which warns neighbors of invasion) 
    • Phagocytes (wandering and fixed macrophages)
    • NK cells
  140. NK cells
    • Natural killer cells
    • a type of lymphocyte
    • make up 5 - 10% of our circulating lymphocytes
    • Along with non-specific phagocytes, their role is to release chemicals from their granules to either induce apoptosis or cause lysis of targeted cell
  141. Two groups of phagocytes in the Second line of defense
    • neutrophils - released in large #'s, very quickly, but life span is short
    • macrophages - first released as monocytes from bone marrow, which enlarge and develop as they migrate to site of infection or injury (called wandering macrophages)
    • fixed macrophages occupy specific tissues
  142. Process of phagocytosis
    • chemotaxis
    • adherence
    • ingestion
    • digestion
    • killing
  143. chemotaxis
    • the phenomenon whereby cells direct their movements according to certain chemicals in their environment
    • Referring to phagocytosis, when an infection begins, the body releases chemicals in order to attract the phagocytes to the site of infection
  144. Kupffer cells
    fixed macrophages of the liver
  145. alveolar macrophages
    fixed macrophages of the lungs
  146. microglial cells
    fixed macrophages of the CNS
  147. Fever
    • Part of our non-specific internal defenses
    • abnormally high body temp due to resetting of hypothalamic thermostat
    • Non-specific response:
    • speeds up body reactions
    • increases effects of endogenous antimicrobials
    • Sequesters nutrients from microbes
  148. inflammation
    • big part of non-specific, non-adaptive, innate response; internal defenses
    • process has three stages: 
    • vasodilation and increased vascular permeability
    • emigration of phagocytes from blood to tissue
    • tissue repair
  149. Local signs & symptoms with inflammation
    • redness
    • pain
    • heat
    • swelling
    • possible loss of tissue funtion
  150. What causes the redness and heat during inflammation?
    • Vasodilation leads to redness and heat due to increased blood flow
    • (only happens in vascular tissue since it's mediated by things coming through blood vessels)
  151. What causes the swelling during inflammation?
    • increased vascular permeability for the emigration of phagocytes
    • also leads to fluid and proteins leaking into the interstitial space and causing swelling
  152. What's the deal with the perception of pain during inflammation?
    • Fluid, histamine, and broken cells release prostaglandins (which cause pain)
    • is the result of targeted free nerve endings by cytokines and pro-inflammatory chemicals
  153. Main players in adaptive immunity system
    • T lymphocytes: include T-helper, T-cytotoxic, T-regulator & memory T-helper and T cytotixic cells
    • B lymphocytes
  154. Lymphocytes
    • type of agranular leukocyte (WBC)
    • They are classified by the location where they mature~
    • T-lymphocytes originate from stem cells in bone marrow, leave as pre-T cells and mature in thymus
    • B-lymphocytes originate and mature in bone marrow
    • *So a lymphocyte will either be a T or B
  155. antigen
    • a substance that is recognized as foreign and reacts with products of the immune system
    • 4 things determine the antigenicity of a substance: 
    • recognition as foreign
    • structural complexity
    • size
    • organic in nature
    • *Recognition as foreign most important - something can fit all the others, but if the body deems it as part of itself, it will leave it alone
  156. hapten
    • a molecule that fits the criteria of an antigen, except for size
    • doesn't trigger immune response (unless it binds w another molecule, making it big enough)
  157. epitopes
    • also called antigenic determinants
    • refers to different sites or antigens on a pathogen
    • can react with the immune system IF IT IS LARGE ENOUGH ~ initiating an immune response
    • A pathogen can have multiple sites (or antigens)
    • *They are antigens which the body see's as foreign so it will induce immune response
  158. What are the subtypes of T lymphocytes
    • *Produced in bone marrow, mature in thymus
    • Divide into:
    • T helper (CD4) cells
    • T-cytotoxic (CD8 - marker on cell) cells
    • T-regulator cells
    • Memory T-helper cells
    • Memory T-cytotoxic cells
  159. "clusters of differentiation"
    • CD for short
    • old name used for T helper & T cytotoxic cells
    • initially researchers though the markers of white cells indicated a specific cell type. Thought they occurred in groups or clusters
  160. T-helper cells
    • also called CD4 T-cells, due to presence of CD4 marker
    • The middle man or main "helper" of immune response ~ act as a co-stimulator for both the B cells and T cytotoxic cells
    • receive info from non-specific phagocytic cells & pass that info on to generate specific response to a particular antigen
    • *part of BOTH cell-mediated and antibody-mediated immunity
  161. T-cytotoxic cells
    • T-cells which destroy abnormal cells
    • virally-infected cells and cancerous cells are main target
    • Also called CD8 T-cells
    • Does cell-to-cell combat & kills bad cells
  162. T-regulator cells
    • keep immune system from getting out of control
    • decrease the reactivity of other types of T-cells
    • essential for maintaining self-tolerance
  163. Memory T-cytotoxic and Memory T-helper cells
    • produced w an initial exposure to an antigen to provide memory of the event and a rapid response if re-exposed to the antigen
    • do not participate in the first time around
  164. Two types of adaptive immunity
    • Cell mediated immunity = Side w T cells
    • Anti-body mediated immunity = humoral side - B cells ( humor meaning fluid: the antibody "missiles" made by B cells travel through blood to get to where they need to go)
    • both triggered by exposure to specific antigens
  165. cell-mediated immunity
    • involves action of T-cytotoxic lymphocytes
    • cell to cell combate
    • detect and destroy abnormal cells
    • Virally-infected cells, cancer cells, and cells infected by intracellular bacteria
  166. antibody-mediated immunity
    • involves action of B-lymphocytes
    • activated to become plasma cells and produce antibody
    • also makes memory
  167. MHC
    • major histocompatibility complex = (Also called HLA) 
    • a group of genes that codes for a group of transmembrane proteins 
    • found on the surface of all nucleated cells
    • Important in processing and presentation of antigen
  168. HLA
    • Human leukocyte antigens = code for transmembrane proteins
    • was the old name for MHC
    • it was originally thought the group of genes that codes for transmembrane proteins only existed on leukocytes
    • Now it's known they are present on all nucleated cells. Therefore, name changed to MHC
  169. Two major types of MHC
    • MHC Class I and MHC Class II
    • are protein molecules
    • could think of them as flag poles that fly a flag to rat out a foreign invader
    • So they present antigen to rest of immune system
  170. MHC class I molecules
    • present on all body cells, except red blood cells (cause they don't have a nucleus)
    • Present antigens that were inside of cell
  171. MHC class II molecules
    • present on surface of antigen-presenting cells (APC's)
    • Present antigens that were outside of cell
  172. APCs
    • Antigen-presenting cells
    • primary responsibility to present antigens to other components of immune system
    • *They are like the sheriff's of immune system
    • commonly phagocytes, but B cells can present antigen
    • Processing differs slightly depending on whether or not the antigen was present outside the body cells or inside
    • *required for cell-mediated and antibody-mediated immunity
  173. Examples of endogenous antigens
    • viral proteins within virally-infected cells
    • toxins from intracellular bacteria
    • abnormal proteins in cancer cells
  174. clonal selection
    • Occurs when a cell proliferates (increases it's numbers) and differentiates (matures)
    • Regarding APC's, it's through this process the active T-helper cells and T-memory cells are produced
  175. General steps for antigen processing and presentation
    • Phagocytosis by antigen-presenting cells
    • Digestion of antigen within vesicle
    • Synthesis of MHC-class molecule
    • Fusion of antigen fragment w MHD-class molecule
    • Insertion of antigen-MHC class complex in the plasma membrane
  176. What happens once an antigen is processed and presented on an APC?....
    as in the flag is being flown?
    • It's ready to meet the T-helper cell
    • Through a specific T-cell receptor, an inactive T-helper cell will bind to antigen fragment (which is being presented by MHC class II molecule)
    • Along with this binding, cytokine stimulation results in the activation and proliferation of the T-helper cell (clonal selection = more T-helpers & T-memory cells)
  177. What happens once an antigen is processed and presented on an infected body cell?
    • An inactive T-cytotoxic cell binds to the abnormal cells presenting viral proteins or cancer proteins on MHC class-I molecule
    • T-helper cells act as a co-stimulator
    • This activates the T-cytotoxic cell, which then also undergoes clonal selection
  178. Activation of B cells
    • Is the last to be activated
    • can be activated by 2 different mechanisms:
    • by direct recognition of antigen through B-cell receptors
    • OR
    • Through T-helper cell activation
    • Once activated, B-cells under go clonal selection - some new B-cell clones will become B-memory cells, others will mature into plasma cells and secrete antibodies specific to the particular antigen
  179. Steps in exogenous antigen processing and presentation
    • Ingestion of antigen
    • Digestion of antigen into fragments
    • Synthesis of MHC class-II molecules
    • Vesicular packaging of class-II molecules
    • Fusion of fragment and class-II molecules
    • Binding of fragments to class-II molecules
    • Insertion of the antigen-MHC class-II complexes in the plasma membrane for recognition
  180. Steps for Endogenous antigen processing and presentation
    • Digestion of antigen into fragments
    • Synthesis of MHC class-I molecules
    • Binding of fragments to class-I molecules
    • Vesicular packaging of class-I molecules
    • Insertion of the antigen-MHC class-I complexes in the plasma membrane for recognition
  181. Ig
    • immunoglobulins = gamma globulins = antibodies
    • produced in response to antigen through antibody-mediated immunity
    • *they actually don't "destroy" anything; instead they signal antigen for destruction, and disable antigen
  182. What is the basic structure of antibodies
    • they have specific structure that provides for their specificity
    • Generally consist of 4 peptide chains: two heavy and two light
    • Disulfide bonds link the chains together in Y-shaped arrangement
    • Most are one Y-shaped unit (monomer)
  183. Two main regions of an antibody:
    Variable region: consists of distal segments of heavy and light chains - forms the antigen binding site (which gives the antibody it's specificity)

    Constant region: differs slightly for the different classes of antibodies
  184. Antibody functions:
    • Neutralizing antigen
    • Immobilizing bacteria
    • Agglutinating and precipitating antigen
    • Activating complement
    • Enhancing phagocytosis
  185. Whats the result from antibodies neutralizing antigen?
    • Neutralizes toxins
    • binds to viruses to restrict their binding to host cells
  186. Whats the result from antibodies immobilizing bacteria?
    Restricts the spread of motile bacteria by binding to cilia or flagella
  187. What's the result from antibodies agglutinating and precipitating antigen?
    • Making what is soluble, insoluble
    • Multiple antigen-binding sites can result in one antibody binding to 2 or more antigen, causing agglutination (clumping of cells)
    • binding may cause soluble antigen to become insoluble
  188. What is the result from antibodies activating complement:
    Antigen/antibody complexes initiate the classical complement pathway
  189. What is the result from antibodies enhancing phagocytosis?
    opsonization (flag for phagocytosis)
  190. Five classes of antibodies
    • IgG
    • IgM
    • IgA
    • IgE
    • IgD
  191. IgG
    • One class of antibody
    • Monomer w two antigen-binding sites
    • 80% of the antibody in the blood
    • Only class that can cross placenta
    • Provide long-term immunity
    • Found in: blood, lymph and intestines
  192. IgM
    • Once class of antibody
    • Pentamer w ten antigen-binding sites
    • First to be secreted by plasma cells
    • great complement activator
    • short-lived response
  193. IgA
    • One class of antibody
    • Dimer w four antigen-binding sites
    • Most numerous in body secretions: sweat, tears, saliva, mucus, breast milk, and gastrointestinal 
    • Levels decrease during stress (so you probably have NONE)
  194. IgE
    • One class of antibody
    • Monomer w two antigen-binding sites
    • less than 0.1% of antibody in blood
    • located on mast cells in tissue
  195. IgD
    • One class of antibody
    • Monomer w two antigen-binding sites
    • 0.2% of antibody in blood
    • acts as antigen receptors on B lymphocytes
  196. Different ways to acquire adaptive immunity
    • Naturally - not gained through modern medicine
    • Artificially - gained through artificial means
    • Actively - body responds to a pathogen to make antibodies (long-term immunity)
    • Passively - body receives antibodies w no effort of it's own
    • Active is long-term; passive is short-term
  197. Methods of acquiring adaptive immunity
    • Naturally-acquired active immunity
    • Naturally-acquired passive immunity
    • Artificially-acquired active immunity
    • Artificially-acquired passive immunity
  198. naturally-acquired active immunity
    • Immune products acquired following exposure to antigen
    • Ex: Hep A stimulated production of anti-hep A antibodies
  199. naturally-acquired passive immunity
    • Transfer of antibody from non-medical source
    • Ex: IgG through the placenta, IgA through breast milk
  200. artificially-acquired active immunity
    • Immune products acquired through vaccination
    • antigens given that are immunogenic but not pathogenic
  201. artificially-acquired passive immunity
    Prepared injection of antibody
  202. the complement system
    • a very powerful group of proteins that "complement" the action of the immune system
    • Main proteins are C1 - C9
    • Activated by multiple pathways in a step-wise or cascading fashion
  203. functions of the complement system
    • Encourages vasodilation and inflammation
    • Antigen opsonization
    • Destroys antigen
  204. How is cellular destruction accomplished in the complement system?
    • by the formation of a membrane-attack complex
    • this is a group of complement proteins that are inserted into the plasma membrane to form a port in the membrane of the microbe
    • This causes extracellular fluid to flow into the cells and the lysis of the microbe
  205. Primary vs. Secondary antibody-mediated response
    • Primary:
    • 1st exposure
    • 5-7 day delay
    • Production of IgM antibodies followed by IgG

    • Secondary:
    • Second & subsequent exposures
    • Very little delay due to memory T-helper and B cells
    • Production of IgM followed by a long-lasting population of IgG
  206. antibody titer
    • is a test that detects the relative amount of antibody
    • indicator for an antibody-mediated response
  207. self-recognition & self-tolerance
    • Self-recognition: ability to recognize one's own cellular markers
    • Self-tolerance: the immune system must leave self-antigens alone

    Failure of self-recognition or self-tolerance results in autoimmune disease
Card Set
HTHS Mod 15
Cardio - Blood, Lymph, and Immunity
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