1. The Lymphatic System and the Blood

2. Overview Why needed? Origin: Blood vessels form from mesoderm
Blood produced 2 wks after vessels are formed, during the 5th week of life

3. What is blood? Connective tissue? Different from others
Matrix not a solid or semi-solid material
Matrix of blood is plasma
watery substance
Yellowish
90% Water
7% protein
1% minerals
2% other materials incl. atmospheric gases, chem signals, and nutrients

4. More on plasma Contains: Atmospheric gases:
oxygen, carbon dioxide, and nitrogen
Comprises 55% of blood volume

5. Formed elements (= Cellular components) Remaining 45% of blood volume:
Erythrocytes (RBCs)
Leukocytes (WBCs)
Thrombocytes (platelets)

6. Hematocrit
Calculates the volume of red blood cells making up the blood Included in a CBC FYI: CBC (on medical shows) = complete blood count

7. Complete Blood Count includes…
Hematocrit
The number of RBCs
The number of WBCs
The total amount of hemoglobin in the blood
Also provides information about the following measurements:
Average red blood cell size (MCV)
Hemoglobin amount per red blood cell (MCH)
The amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell (MCHC)
The platelet count is also usually included in the CBC. 

8. Can you answer these questions?
What is the blood composed of?
Why is the blood unlike any other connective tissue?
What does a hematocrit tell you?

9. Red Blood Cells

10. Red Blood Cells No mature nucleus (lost in dev.) No DNA, so….
Use enzymes to carry out their tasks
Reticulocytes (immature RBC) – have mesh-like network of rRNA… become mature in ~24 hours
Live max 120 days
No way to repair & replace damaged cellular components
Appear red b/c of hemoglobin
Contains iron  facilitates transport of
O2 and CO2
4.8 million RBC/mm3 in women
5.4 million RBC/mm3 in men

11. Blood Type
Genetic
Determined by the antigens on the surface of the RBC membrane
A,B,O blood group system most common (30 possible in full blood type classification!)
Blood will attack “non-self”
Important to match blood types for transfusions
Therefore…
AB universal acceptor
O universal donor-has no proteins on the membrane

13. Rh Factor The “D” protein Most are positive (depends on geography)
If a woman is negative and conceives with a positive man, problems can arise— erythroblastosis fetalis

14. This can lead to anemia, a condition marked by weakness and fatigue
This can lead to anemia, a condition marked by weakness and fatigue. Severe anemia can lead to heart failure and death. The breakdown of RBC leads to the buildup of bilirubin which can lead to jaundice and brain damage.

15. Prevention of erythroblastosis fetalis
Treat negative mothers with Rhogam, a preventative measure
Prevents formation of antibodies to Rh molecule
Given whenever there is a possibility of fetal blood mixing with maternal blood following childbirth, abortion, miscarriage, prenatal testing.
Once sensitized the woman will always react against Rh+ cells

16. Can you answer these questions?
How are RBCs different from most other cells?
How does the lack of a nucleus affect RBCs lifespan?
What is hemoglobin and what does it do?
Why are RBCs red?
What is blood type? What do the different blood types mean?
Why is it dangerous for an Rh- woman to have an Rh+ baby?

17. White Blood Cells

18. White Blood Cells WBC : RBC ratio = 1 : 500 or 1000
Use blood, lymph to move from bone marrow to the tissues
5 types (differential WBC count measures them)
Neutrophils (Most abundant)
Lymphocytes
Eosinophils
Monocytes
Basophils (Least abundant)

19. WBC’s Agranulocytes Granulocytes AKA : Mononuclear
Noticeable granules that produce specialized secretions for fighting infection
Lack visible granules in cytoplasm
Nucleus is polymorphic, lobed, unusually shaped
Monocytes
Lymphocytes
Eosinophils, basophils, neutrophils
T & B cells

20. Neutrophils Granulocyte Most common WBC Nucleus = 2-5 lobes
Found in the blood
First responders in the inflammation response due to environmental exposure, some cancers, bacterial infection
 Predominant cell in pus

21. Eosinophils Granulocyte 5% of WBCs Bi-lobed nucleus
Combats parasitic infections (protists, worms)
Secretions produced related to allergies
Normally in thymus GI, ovaries, testes, spleen, uterus, lymph nodes
NOT in lungs, esophagus, or skin  if found here, indicates disease/pathology

22. Basophils Granulocyte (least common) Susceptible to basic dyes
Large, bi-lobed nucleus (similar to mast cells)
Granules obscure the nucleus
“Bas-ically all granules”
Involved in allergies.
Stores, secrete histamine & heparin (anticoagulant)
Found where allergic reactions are taking place

23. Agranulocytes Lymphocytes “Immune” cells:
NK (natural killer) cells (no prior activation needed)
T lymphocytes (mature in thymus)
Helper: direct immune response
Cytotoxic: release cytotoxin to kill pathogen infected cells
B lymphocytes (mature in bone marrow): Use antibodies to neutralize pathogens

24. Monocytes Agranulocyte Largest of WBCs - shaped nucleus
Mono = kissing = Love = heart
Many vesicles in cytoplasm for processing pathogens
Perform phagocytosis - uptake & digestion of pathogens
Fragments of “eaten” pathogen signal T-lymphocytes to the area

25. Platelets Cell fragments derived from larger cells called
megakaryocytes.
Have “sticky” proteins
Reduce blood flow to an affected area.
Reduce blood loss
Sensitive to many types of hazardous chemicals and pollutants

27. Can you answer these questions?
Describe the characteristics & functions of all granulocytes, agranulocytes, and platelets.
Compare and contrast the structure & function of RBCs and WBCs
Why are platelets called the “Band-Aids” of the blood?

28. Blood Cell Function

29. Red Blood Cell Function
Carry oxygen from the lungs to the body
Carry carbon dioxide from the body to the lungs

30. RBC in the capillaries that surround the alveoli oxygen enters
Alveoli-where gas
exchange happens in
the lungs
RBC in the capillaries that surround the alveoli oxygen enters
Only if the partial pressure of oxygen outside is higher than inside
In cytoplasm of RBC oxygen binds to Hemoglobin

31. Hemoglobin Four oxygen molecules bind to hemoglobin (w/ the iron)
Carries CO2 also;
binds to a different area than O2
Percent saturation:
amount of oxygen that is dissolved in a solution of hemoglobin molecules
O2 sats = 98% or above
Similar to with myoglobin in muscle
Greater affinity for oxygen
Hemoglobin collects oxygen a low partial pressures

32. In the tissues the oxygen is released and carbon dioxide enters the RBC, binds to Hemoglobin.
Partial pressures of the gases must appropriate
Some cellular wastes stimulate the release of the oxygen from the hemoglobin
Allows RBC to give more O2 to tissues w/ high metabolic needs

33. Carbon Dioxide Carried 3 ways in the blood
1. Carried in the blood as a gas (10%)
2. Binds to empty hemoglobin: carbaminohemoglobin
3. As a bicarbonate ion (HCO3-)
CO2 can dissolve in water, forming bicarbonate ion
Dissolves in the blood plasma
Carbonic anhydrase: enzyme in RBC that stim’s the formation of carbonic anhydrase, which dissociates to form bicarbonate ions and H+ ions
Eventually excreted

34. Movement of gases Diffusion: High concentration  low concentration
For Oxygen:
Partial pressure is higher in blood than in tissues
For Carbon Dioxide:
Partial pressure is higher in tissues than in blood

35. Carbon dioxide intoxication
Occurs when the CO2 is extremely high in the environment or the blood
Acute: high levels in the air
Subacute: toxicity caused by the body’s failure to eliminate carbon dioxide
Decreases blood’s pH (what kind of acid does CO2 form when it dissolves in water?)
Carbonic acid!

36. Can you answer these questions?
What is the purpose of RBCs?
Where does oxygen bind to the Hb molecule?
Where does Hb collect oxygen? Then what happens?
Describe the partial pressures that must be present for oxygen to diffuse from RBC to tissues and for carbon dioxide to move to the cells?

37. White Blood Cell Function
In general:
Fight infections & disease
Granulocytes:
granules of toxic chemicals that kill microorganisms
regulate reactions to foreign materials in the body

38. Neutrophil function Pass through capillaries to
tissues to with infections.
Attracted to affected areas by factors secreted by damaged cells/tissues
Stick to injured tissues, use phagocytosis to engulf remains of bacteria and damaged cells
Secretes antibiotics-harms/kills bacteria
Secretes other chemicals that stim.
Inflammation ↑ blood flow to the area & ↑ WBC concentration

39. Eosinophil function Secretions defend against
parasitic infections esp. protists
& worms
↑ in eosinophils = parasitic infection
Granules contain major basic protein to kill the parasites
Secrete chemicals associated w/ allergies

40. Basophil function Secrete histamine  stim the immune response
Overproduction of histamine  runny nose, sneezing, watery eyes
Mast cells (special kind of basophil)
Cause inflammation of tissues
Secrete chemical that attract neutrophils
Found in walls of small bl. vessels

41. Monocyte function Clear granules give cytoplasm a grey appearance
When they leave the bone marrow they become either:
Circulating monocytes
Detect infections in blood
Bone growth & maintenance
Tissue monocytes (macrophages)
Remove dead cells
Attack microorganisms that are difficult to kill (fungi)

42. Lymphocyte function Stay tuned! We’ll talk about it later….for now,
they carry out most of the
duties of the immune system

43. Can you answer these questions?
Which WBC is in charge of engulfing bacteria?
Which WBC is in charge of protecting us from parasites?
Which WBC differentiates into cells that assist in bone growth and maintenance or are macrophages that protect against fungal infections?
Which WBC secretes major basic protein?

44. Platelets’ function Blood clotting
Platelets adhere to injured area
Activation of blood clot formation
Important that clot forms by injury only
Intact cells secrete prostacyclin (prevents platelet activation)

45. Clotting Cascade

47. Clotting Cascade (simplified)
1.) BV damaged, releases “distress chemicals”
2.) Clotting factors stim. other factors that indicates presence of damaged tissues
a.) platelets stick to damaged tissues & each other
b.) Platelets secrete prothrombin activator & Ca2+
Catalyze conversion of prothrombin to thrombin
c.) Thrombin causes fibrinogen  fibrin
d.) Fibrin forms a sticky mesh that adheres to thrombocytes and other blood components (clot)
Clot forms a barrier that prevents blood loss & impedes the passage of microorganisms into tissues
Calcium ions = catalyze PT to T
Vitamin K = synthesis of clotting factors
Prothrombin
Thrombin
Fibrinogen
Fibrin

48. Why is the cascade so complicated?
So the blood doesn’t clot unintentionally!
They aren’t permanent
Plasminogenplasmin (digests fibrin and dissolves a clot)
Healthy cells near the clot secrete TPA (tissue plasminogen activator)dissolves fibrin as well.

49. Can you answer these questions?
1.) What is the purpose of prostacyclin? 2.) What is the purpose of a clot? 3.) What are the steps of the clotting cascade? 4.) What is the role of calcium and vitamin K in clot formation? 5.) Why is the clot cascade so complex? 6.) What do plasmin and tissue plasminogen have in common? What’s the difference?

50. Blood Cell Formation

51. In General… Adults: bone marrow Embryo: Liver
Different forms of Hb throughout development allow fetus to adapt to varying metabolic needs for oxygen
11 million/sec in an adult
1 WBC produced for every ~500 RBCs

52. In General… Adults: bone marrow Embryo: Liver
11 million/sec in an adult
1 WBC produced for every 700 RBCs GF GF
Hematopoietic stem cell Or
Multipotent stem cell
Pluripotent stem cell
Lympohid give rise to WBC of lymphatic system
Myeloid give rise to platelets, RBCs, and WBCs that circulate in the blood
Growth factors: stimulate the production of a particular blood cell lineage
Growth factors from various organs regulate the formation of blood cells
Myeloid stem cell (progenitor)
Lymphoid stem cell (progenitor)

54. The life history of erythrocytes (RBCs)
Blood oxygen decreases
Stimulates erythropoietin production from kidneys and liver
Erythropoietin  Erythropoiesis in red bone marrow (where is this found?)
Immature erythrocytes have a large nucleus
Hb production begins in basophilic erythroblasts
Reticulocytes: lose nucleus, after 1-2 days in circulation lose organelles

55. Erythropoeisis
If the need for oxygen is great, erythropoiesis will occur at an increased rate.
This means an increased amount of polychromatic erythroblasts will enter the blood stream
Erythropoiesis of a single erythrocyte takes approximately 4 days

56. Normal bone marrow has an abundance of newly formed RBCs and megakaryocytes (which produce platelets)

57. Old erythrocytes get gobbled up!
Removed by macrophages
Globin (protein) is broken into individual amino acids & recycled
Iron is recycled
Parts of the molecule are converted to bilirubin
Processed in liver, secreted in bile in small intestine
Bacteria convert into pigments feces color
Some excreted in urine yellow color

58. A bit about WBCs: Lifespan = 13-20 days
Destroyed in lymphatic system
When released from bone marrow called stabs or bands
Esp. neutrophils b/c their nuclei aren’t lobed, yet, and look like a rod (stab = German for rod) or bands

59. The Lymphatic System

60. Functions of Lymphatic System
1.) Maintain fluid balance in the tissues
30L fluid from capillaries to interstitial and only 27L pass from interstitial back into capillaries qd (every day)
If fluid left in the body  tissue damage
3L fluid enter lymph capillaries, called lymph
Then to lymph vessels & return to blood
2.) Absorb fats & other substances from digestive tract (chyle)
3.) Defense
Nodes filter lymph & spleen filters blood of microorganisms & foreign substances

61. Lymphatic System Structures
Like plasma: ions, nutrients,
wastes from interstitial spaces
Hormones, enzymes from cells in tissues
Lymphocytes
Lymph vessels
Flow of lymph produced by gravity
or skeletal muscle, passively drains
to lower body from upper
Valves-no backflow
Lymphatic trunks drain lymph from larger areas of body
Clusters of lymphatic tissue

62. Lymphatic System Structures
Lymph nodes
Collections of lymphatic tissue covered by connective-tissue capsules
Eliminate antigens from lymph as lymph flows thru the node.
In groups along the larger lymphatic vessels

63. Lymph node structure 2 divisions: Cortex (outer) & Medulla (inner)
Has “compartments” called lymphatic nodules
2 layers: inner layer called germinal center where B-lymphocytes are found. In the “wall” surrounding the germinal center is where T-lymphocytes are found.
Nodules are sep’d by trabeculae—extensions of the capsule—fibrous covering of the node
Cortical sinus: spaces where lymph flows through
Medulla
Medullary sinus = space where lymph flows throught he center of the node, contains macrophages
Medullary cord = contains lymphocytes

64. Capsule covers.
Extension of capsule = trabeculae
Reticular fibers, macrophages, and lymphocytes form lymphatic tissue
Outside layer: cortex
Inner layer: medulla
Cortex & medulla have open spaces called sinuses, lined with phagocytic cells that remove bacteria and other foreign material
Efferent and afferent lymph vessels. Afferent = enter via cortex. Efferent = exit from opposite side
Cells of lymph nodes consist of lymphocytes, macrophages and reticular cells. Microorganisms or other foreign substances in the lymph can stimulate lymphocytes throughout the lymph node to undergo cell division with proliferation esp. evident in the lymph nodules of the cortex. Areas of rapid lymphocyte division are germinal centers.
Newly produced lymphocytes are released into the lymph and eventually reach the blood stream where they circulate, can enter other lymph tissues
Efferent Blood vessels enter via hilum
Lymph vessels enter thru various openings in the capsule and exit via hilum

65. Lymphatic System Structures
Tonsils
Swollen cluster of lymphatic tissue in throat
Form protective ring of lymphatic tissue around the openings between the nasal and oral cavities & pharynx
Provide protection against bac and other harmful material
Eventually disappear in adults
Spleen
Detects and responds to foreign substances in the blood
Destroys worn out red blood cells
Acts as a blood reservoir
Structure
Left side of the extreme superior, posterior corner of ab cavity
White pulp: Contains T & B lymphocytes
Assist body with infections that require a large immune response
Red pulp: removes old/damaged RBCs

66. Lymphatic System Structure
Thymus
Deep to manubrium
In newborn, extends length of thorax & grows until puberty, then decreases in size
Function
Produce lymphocytes that move to other lymph tissues, but most degenerate before moving on
Produces secretions that mature T-lymphocytes
Can’t destroy normal body cells (Self-tolerance)

67. Immune Response

68. Immunity words to know:
Antigen: a substance that can
induce an immune response.
Hapten: A molecule that can cause an immune response when attached to blood proteins.
Two ways the immune system can respond to disease:
Innate immunity
Acquired immunity

69. Why an immune system?
We are outnumbered! Viruses and bacteria are everywhere!
Humans offer limitless resources for pathogens
Energy
Reproductive potential
Getting into the body isn’t easy!

70. Meet the enemy Bacteria Viruses (And fungi, protozoa too…) Free-living
Not all are bad!
Pathogenic ones produce toxins that damage human tissue
Viruses
Obligate parasites
Hijack human cells; convert to virus-producers, killing host cell in the process
(And fungi, protozoa too…)

71. A human fortress: Prevention
Skin is thick – hard to penetrate
Produces substances that deter invasion:
Skin pH (not favorable)
Mucus (sticky trap)
Lysozymes (digest bacteria)
Specialized traps around vulnerable areas (Eyes, nose, mouth)
Cilia sweep away invaders that are
trapped
Stomach acid kills ingested invaders

72. …but we do get sick! Enter through weak points:
Food
Nose
Break in skin/scrapes
Cells are damaged/destroyed
Dying cells release distress chemicals (histamine)
Triggers inflammation (blood vessel dilation, increased blood flow)
Draws defensive cells to area (generalized white blood cells)

73. How do we tell “friend” from “foe”?
All cells present antigens – surface protein molecules that identify identity
(antigen = antibody generator)
Immune system reacts to foreign antigens

74. A complex system! Several “lines” of defense:
Barriers (First line of defense)
Generalized defenders (Second line of defense)
Specific defenders AND memory (Third line of defense)
Consist of:
Several types of cells
Proteins

75. The Complement System Part of second line of defense
Free-flowing proteins found in blood
Quickly reach site of invasion
React to antigens
When activated, can
Trigger inflammation
Attract “eater cells” (macrophages)
Coat pathogen (make macrophages’ job easier)
Kill intruder directly

76. Phagocytes
Find and “eat” bacteria, viruses, dead/injured body cells by phagocytosis
3 types:
Neutrophils
Macrophages
Dendritic cells

77. Neutrophils Often first to site of infection Numerous Short lifespan
“Pus” in infected wounds chiefly composed of neutrophils

78. Macrophage “Big eaters” Slower to respond to invader than neutrophil
Larger, longer-lived, more capable
Help alert rest of immune system to invader
Start as monocytes; become macrophages when entering bloodstream

79. Dendritic cells “Eater” cells
Help with immune system activation – act as antigen-presenting cells
Filter bodily fluids to clear foreign organisms and particles

80. Lymphocytes: Third Line of Defense
T and B cells
Originate in bone marrow
Migrate to lymph nodes, spleen, thymus to mature
Lymph vessels
transport, store lymphocytes
Feeds cells into body
Filter out dead cells/invading organisms

81. Receptors Each lymphatic cell contains surface receptors
Recognize foreign antigens
Specialized for a particular antigen

82. T cells
Two types: helper and killer
T = thymus
Mature here

83. Helper T cell Main regulator of third line of defense
Primary task: activate B cells and killer T cells
Activated by macrophages/dendritic cells (antigen presentation)

84. Killer T cell Attacks body cells infected by pathogen, cancer cells
Receptors used to determine if each cell encountered is self/non-self (compare to accepted receptors, MHC)

85. B lymphocyte cell Searches for antigens matching receptor
If a match is found…
Connects to antigen
Triggering signal set off…
T helper proteins help fully activate B cell
Produces 1000’s of clones: differentiate into plasma cells or B memory cells

86. Plasma Cell Produces antibodies
Responds to same antigen matched by B cell receptor
Seek out intruders, help destroy them
Release tens of thousands/second

87. Antibodies Y-shaped Attach to matching antigens
Enhance phagocytosis of macrophages (label for capture)
Neutralize toxins
Incapacitate viruses (coat surface proteins)
Group pathogens by linking (agglutination)

88. Immunoglobins
IgG: most common, fight general infections, pass from mom to child in pregnancy (G= mom’s gift)
IgA: in mucous membranes of the digestive system, milk, tears, saliva (A= a lot of mucus)
IgM: natural defenses against general bacterial infections (M=most bacteria)
IgE: stim basophils and mast cells to defend against parasites fungi and worms (E=eeww!)
IgD: on membranes of B-lymphocytes, form plasma and memory cells (D=defend blood)

89. Memory cells Prolonged lifespan “Remember” specific intruders
Both B and T cells have memory cells
Helps trigger immune system to respond more quickly if invader reappears

90. Inflammation Outcome of acquired immune response
Increases blood circulation to affected area
Bv’s dialate to increase blood flow
Immune cells go to injured area
Immune resp. takes place at the site it’s needed
Tissues = red and warm b/c of the blood that enters the area, ↑ in temp = anti-microbial
Pain from pressure of swollen tissues on nerve endings
Normal functions return when the tissue is fully recovered

91. Immunization & Vaccination

92. Natural Immunity
Natural: exposed to foreign antigens as a part of everyday life.
Active immunity – body responds to foreign antigens and develops immunity using B and T lymphocytes
Passive immunity –
Embryological development when antibodies (Ig’s) from the mother’s blood stream are passed to the fetus
Breastfeeding – baby receives antibodies via milk

93. Artificial Immunity Active: Immunization Passive: Antibody Transfer
Therapeutic exposure to antigens
Stimulates the primary response by introducing pathogenic material (inactivated, attenuated, or partial) into the body
Vaccines are typically used for viruses! Antibiotics are only for bacteria
Passive: Antibody Transfer
Patient receives (via injection) large amounts of antibodies to fight disease
Globulin injections can remove certain microorganisms from the body.