overview why needed? origin: blood vessels form from mesoderm blood produced 2 wks after vessels...
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THE LYMPHATIC SYSTEM AND THE
BLOOD
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Overview
Why needed? Origin:
Blood vessels form from mesodermBlood produced 2 wks after vessels are
formed, during the 5th week of life
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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
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More on plasma
Contains: Atmospheric gases:
oxygen, carbon dioxide, and nitrogen
Comprises 55% of blood volume
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Formed elements
(= Cellular components)
Remaining 45% of blood volume:
Erythrocytes (RBCs)Leukocytes (WBCs)Thrombocytes (platelets)
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Hematocrit
Calculates the volume of red blood cells making up the blood
Included in a CBC
FYI: CBC (on medical shows) = complete blood count
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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.
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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?
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Red Blood Cells
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Red Blood Cells No mature nucleus (lost in dev.) No DNA, so….
○ Use enzymes to carry out their tasksReticulocytes (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 women5.4 million RBC/mm3 in men
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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 acceptorO universal donor-has no proteins on the membrane
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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
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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.
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Prevention of erythroblastosis fetalis
Treat negative mothers with Rhogam, a preventative measurePrevents 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
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Can you answer these questions?
1. How are RBCs different from most other cells?
2. How does the lack of a nucleus affect RBCs lifespan?
3. What is hemoglobin and what does it do?
4. Why are RBCs red?
5. What is blood type? What do the different blood types mean?
6. Why is it dangerous for an Rh- woman to have an Rh+ baby?
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White Blood Cells
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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)LymphocytesEosinophilsMonocytesBasophils (Least abundant)
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WBC’s
Agranulocytes Granulocytes
Nucleus is polymorphic, lobed, unusually shaped
Noticeable granules that produce specialized
secretions for fighting infection
Lack visible granules in cytoplasm
AKA : Mononuclear
Monocytes
Eosinophils, basophils, neutrophils
Lymphocytes
T & B cells
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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
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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
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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
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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
cellsB lymphocytes (mature in bone marrow): Use
antibodies to neutralize pathogens
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Monocytes
Agranulocyte Largest of WBCs - shaped nucleus
Mono = kissing = Love = heart Many vesicles in cytoplasm for processing
pathogens Perform phagocytosis - uptake & digestion of
pathogensFragments of “eaten” pathogen signal T-
lymphocytes to the area
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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
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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?
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Blood Cell Function
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Red Blood Cell Function
Carry oxygen from the lungs to the body Carry carbon dioxide from the body to
the lungs
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Alveoli-where gas
exchange happens in
the lungs RBC in the capillaries that surround the
alveoli oxygen entersOnly if the partial pressure of oxygen
outside is higher than inside In cytoplasm of RBC oxygen binds to
Hemoglobin
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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 moleculesO2 sats = 98% or above
Similar to with myoglobin in muscleGreater affinity for oxygenHemoglobin collects oxygen a low
partial pressures
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In the tissues the oxygen is released and carbon dioxide enters the RBC, binds to Hemoglobin. Partial pressures of the gases must appropriateSome cellular wastes stimulate the release of the
oxygen from the hemoglobin○ Allows RBC to give more O2 to tissues w/ high
metabolic needs
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Carbon Dioxide
Carried 3 ways in the blood1. 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 plasmaCarbonic anhydrase: enzyme in RBC that stim’s the formation
of carbonic anhydrase, which dissociates to form bicarbonate ions and H+ ions- Eventually excreted
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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
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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 dioxideDecreases blood’s pH (what kind of acid
does CO2 form when it dissolves in water?)○ Carbonic acid!
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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?
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White Blood Cell Function In general:
Fight infections & diseaseGranulocytes:
○ granules of toxic chemicals that kill microorganisms
○ regulate reactions to foreign materials in the body
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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
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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
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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 neutrophilsFound in walls of small bl. vessels
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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)
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Lymphocyte function
Stay tuned! We’ll
talk about it later….for now,
they carry out most of the
duties of the immune system
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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?
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Platelets’ function
Blood clottingPlatelets adhere to injured areaActivation of blood clot formation
Important that clot forms by injury onlyIntact cells secrete prostacyclin (prevents platelet
activation)
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Clotting Cascade
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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
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Why is the cascade so complicated?
So the blood doesn’t clot unintentionally! They aren’t permanent Plasminogenplasmin (digests fibrin and
dissolves a clot) Healthy cells near the clot secrete TPA
(tissue plasminogen activator)dissolves fibrin as well.
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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?
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Blood Cell Formation
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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
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In General…
Adults: bone marrow Embryo: Liver 11 million/sec in an adult 1 WBC produced for every 700 RBCs
Hematopoietic stem cellOr
Multipotent stem cellOr
Pluripotent stem cellMyeloid stem cell
(progenitor)
Lymphoid stem cell
(progenitor)
GF GF
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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
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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
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Normal bone marrow has an abundance of newly formed RBCs and megakaryocytes (which produce platelets)
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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
bilirubinProcessed in liver, secreted in bile in small
intestine○ Bacteria convert into pigments feces color○ Some excreted in urine yellow color
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A bit about WBCs:
Lifespan = 13-20 days Destroyed in lymphatic system
When released from bone marrow called stabs or bandsEsp. neutrophils b/c their nuclei aren’t lobed,
yet, and look like a rod (stab = German for rod) or bands
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The Lymphatic System
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Functions of Lymphatic System1.) 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
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Lymphatic System Structures Lymph
Like plasma: ions, nutrients,
wastes from interstitial spacesHormones, 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 bodyClusters of lymphatic tissue
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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
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Lymph node structure 2 divisions: Cortex (outer) & Medulla (inner)
Cortex○ 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 throughMedulla
○ Medullary sinus = space where lymph flows throught he center of the node, contains macrophages
○ Medullary cord = contains lymphocytes
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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
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Lymphatic System Structure Thymus
Deep to manubriumIn newborn, extends length of thorax & grows until
puberty, then decreases in sizeFunction
○ Produce lymphocytes that move to other lymph tissues, but most degenerate before moving on
○ Produces secretions that mature T-lymphocytesCan’t destroy normal body cells (Self-tolerance)
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Immune Response
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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 immunityAcquired immunity
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Why an immune system? We are outnumbered! Viruses and
bacteria are everywhere! Humans offer limitless resources for
pathogens EnergyReproductive potential
Getting into the body isn’t easy!
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Meet the enemy
BacteriaFree-livingNot all are bad!Pathogenic ones produce toxins that damage
human tissue Viruses
Obligate parasitesHijack human cells; convert to virus-
producers, killing host cell in the process (And fungi, protozoa too…)
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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
trappedStomach acid kills ingested invaders
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…but we do get sick! Enter through weak points:
FoodNoseBreak 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)
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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
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A complex system!
Several “lines” of defense:
1. Barriers (First line of defense)
2. Generalized defenders (Second line of defense)
3. Specific defenders AND memory (Third line of defense)
Consist of: Several types of cells Proteins
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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 inflammationAttract “eater cells” (macrophages)Coat pathogen (make macrophages’ job easier)Kill intruder directly
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Phagocytes
Find and “eat” bacteria, viruses, dead/injured body cells by phagocytosis
3 types: NeutrophilsMacrophagesDendritic cells
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Neutrophils
Often first to site of infection Numerous Short lifespan “Pus” in infected wounds chiefly
composed of neutrophils
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Macrophage
“Big eaters” Slower to respond to invader than
neutrophilLarger, longer-lived, more capable
Help alert rest of immune system to invader
Start as monocytes; become macrophages when entering bloodstream
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Dendritic cells
“Eater” cells Help with immune system activation –
act as antigen-presenting cells Filter bodily fluids to clear foreign
organisms and particles
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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 lymphocytesFeeds cells into bodyFilter out dead cells/invading organisms
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Receptors
Each lymphatic cell contains surface receptors Recognize foreign antigensSpecialized for a particular antigen
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T cells
Two types: helper and killer T = thymus Mature here
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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)
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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)
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B lymphocyte cell
Searches for antigens matching receptor If a match is found…
Connects to antigenTriggering signal set off…
○ T helper proteins help fully activate B cellProduces 1000’s of clones: differentiate into
plasma cells or B memory cells
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Plasma Cell
Produces antibodies Responds to same antigen matched by
B cell receptorSeek out intruders, help destroy themRelease tens of thousands/second
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Antibodies
Y-shaped Attach to matching antigens
Enhance phagocytosis of macrophages (label for capture)
Neutralize toxinsIncapacitate viruses (coat surface proteins)Group pathogens by linking (agglutination)
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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)
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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
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Inflammation Outcome of acquired immune response Increases blood circulation to affected area
Bv’s dialate to increase blood flowImmune cells go to injured areaImmune resp. takes place at the site it’s neededTissues = red and warm b/c of the blood that enters
the area, ↑ in temp = anti-microbialPain from pressure of swollen tissues on nerve
endingsNormal functions return when the tissue is fully
recovered
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Immunization & Vaccination
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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 lymphocytesPassive immunity –
○ Embryological development when antibodies (Ig’s) from the mother’s blood stream are passed to the fetus
○ Breastfeeding – baby receives antibodies via milk
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Artificial Immunity Active: Immunization
Therapeutic exposure to antigensStimulates 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 TransferPatient receives (via injection) large amounts of
antibodies to fight disease○ Globulin injections can remove certain microorganisms
from the body.