THE LYMPHATIC SYSTEM AND THE

BLOOD

Overview

Why needed? Origin:

Blood vessels form from mesodermBlood produced 2 wks after vessels are

formed, during the 5th week of life

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

More on plasma

Contains: Atmospheric gases:

oxygen, carbon dioxide, and nitrogen

Comprises 55% of blood volume

Formed elements

(= Cellular components)

Remaining 45% of blood volume:

Erythrocytes (RBCs)Leukocytes (WBCs)Thrombocytes (platelets)

Hematocrit

Calculates the volume of red blood cells making up the blood

Included in a CBC

FYI: CBC (on medical shows) = complete blood count

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. 

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?

Red Blood Cells

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

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

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

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.

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

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?

White Blood Cells

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)

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

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

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

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

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

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

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

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?

Blood Cell Function

Red Blood Cell Function

Carry oxygen from the lungs to the body Carry carbon dioxide from the body to

the lungs

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

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

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

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

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

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!

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?

White Blood Cell Function In general:

Fight infections & diseaseGranulocytes:

○ granules of toxic chemicals that kill microorganisms

○ regulate reactions to foreign materials in the body

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

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

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

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)

Lymphocyte function

Stay tuned! We’ll

talk about it later….for now,

they carry out most of the

duties of the immune system

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?

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)

Clotting Cascade

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

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.

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?

Blood Cell Formation

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

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

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

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

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

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

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

The Lymphatic System

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

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

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

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

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

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)

Immune Response

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

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!

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…)

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

…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)

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

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

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

Phagocytes

Find and “eat” bacteria, viruses, dead/injured body cells by phagocytosis

3 types: NeutrophilsMacrophagesDendritic cells

Neutrophils

Often first to site of infection Numerous Short lifespan “Pus” in infected wounds chiefly

composed of neutrophils

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

Dendritic cells

“Eater” cells Help with immune system activation –

act as antigen-presenting cells Filter bodily fluids to clear foreign

organisms and particles

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

Receptors

Each lymphatic cell contains surface receptors Recognize foreign antigensSpecialized for a particular antigen

T cells

Two types: helper and killer T = thymus Mature here

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)

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)

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

Plasma Cell

Produces antibodies Responds to same antigen matched by

B cell receptorSeek out intruders, help destroy themRelease tens of thousands/second

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)

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)

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

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

Immunization & Vaccination

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

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.