chapter 21&22
DESCRIPTION
LymphaticTRANSCRIPT
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Chapter 21
Blood Vessels and
Hemodynamics
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Blood Vessel Types
• Arteries – carry blood away from the heart
Large elastic arteries (>1 cm); medium
muscular arteries (0.1 – 10 mm); arterioles
(< 0.1 mm)
• Capillaries – site of nutrient and
gas exchange
• Veins – carry blood towards
the heart
Venules are small veins (< 0.1 mm)
Vessel Structure and Function
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All blood and lymph vessels in the body share
components of 3 basic layers or “tunics”
which comprise the vessel wall:
• Tunica interna
(intima)
• Tunica media
• Tunica externa
Vessel Structure and Function
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Vessel Structure and Function
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Medium sized muscular (distributing)
arteries have more smooth muscle in their
tunica media.
• Muscular arteries help maintain the
proper vascular tone to ensure efficient
blood flow to the distal tissue beds.
• Examples include the brachial artery in
the arm and radial artery in the forearm.
Vessel Structure and Function
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Vessel Structure and Function An anastomosis is a union of vessels supplying
blood to the same body tissue. Should a blood
vessel become occluded, a vascular
anastomosis provides
collateral circulation (an alternative
route) for blood to reach a tissue.
• The shaded area in this graphic
shows overlapping blood
supply to the ascending colon.
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Vessel Structure and Function Arterioles deliver blood to capillaries and
have the greatest collective influence on both
local blood flow and on overall blood pressure.
• They are the primary "adjustable nozzles”
across which the greatest drop
in pressure occurs.
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Capillaries are the only sites in the entire
vasculature where gases, water and
other nutrients are
exchanged.
Venules and veins have
much thinner walls than
corresponding arterioles
and arteries of similar size.
Vessel Structure and Function
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Vessel Structure and Function The terminal end of an arteriole tapers toward
the capillary junction to form a single
metarteriole.
• At the metarteriole-capillary junction, the
distal most muscle cell forms the
precapillary sphincter
which monitors and
regulates blood flow
into the capillary bed.
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Vessel Structure and Function
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Vessel Structure and Function
The body contains
three types of
capillaries:
• Continuous
capillaries
• Fenestrated
capillaries
• Sinusoids
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Vessel Structure and Function
• Intravenous pressure
in venules (16 mmHg)
is less than half that
of arterioles (35
mmHg), and drops to
just 1-2 mmHg in
some larger veins.
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Fluid Exchange - Starling Forces As blood flows to the tissues of the body,
hydrostatic and osmotic forces at the
capillaries determine how much fluid leaves the
arterial end of the capillary and how much is
then reabsorbed at the venous end. These are
called Starling Forces.
• Filtration is the movement of fluid through the
walls of the capillary into the interstitial fluid.
• Reabsorption is the movement of fluid from
the interstitial fluid back into the capillary.
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Fluid Exchange - Starling Forces Two pressures promote filtration:
• Blood hydrostatic pressure (BHP) generated
by the pumping action of the heart -
decreases from 35 to 16 from the arterial to
the venous end of the capillary
• Interstitial fluid osmotic pressure (IFOP),
which is constant at about 1 mmHg
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Fluid Exchange - Starling Forces Two pressures promote reabsorption:
• Blood colloid osmotic pressure (BCOP) is due
to the presence of plasma proteins too large
to cross the capillary - averages 36 mmHg on
both ends.
• Interstitial fluid hydrostatic pressure (IFHP) is
normally close to zero and becomes a
significant factor only in
states of edema.
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Fluid Exchange - Starling Forces
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Fluid Exchange - Starling Forces Normally there is nearly as much fluid
reabsorbed as there is filtered.
• At the arterial end, net pressure is outward at
10 mmHg and fluid leaves the capillary
(filtration).
• At the venous end, net pressure is inward at –
9 mmHg (reabsorption).
• On average, about 85% of fluid filtered is
reabsorbed.
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Fluid Exchange - Starling Forces Fluid that is not reabsorbed (about 3L/ day for
the entire body) enters the lymphatic vessels
to be eventually returned to
the blood.
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Gas And Nutrient Exchange
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The volume of blood returning through the
veins to the right atrium must be the same
amount of blood pumped into the arteries from
the
left ventricle – this is
called the venous return.
• Besides pressure, venous
return is aided by the
presence of venous valves,
a skeletal muscle pump,
and the action of breathing.
Venous Return
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The skeletal muscle pump uses the action of
muscles to milk blood in 1 direction (due to
valves).
The respiratory pump uses the negative
pressures in the thoracic and abdominal
cavities generated during
inspiration to pull
venous blood towards
the heart.
Venous Return
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Proximalvalve
Distalvalve
1
Proximalvalve
Distalvalve
1 2
Proximalvalve
Distalvalve
1 2 3
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Although the venous circulation flows under
much lower pressures than the arterial side,
usually the small pressure differences
(venule 16 mmHg to
right atrium 0 mmHg),
plus the aid of muscle
and respiratory pumps
is sufficient.
Venous Return
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Pressure, Flow, And Resistance Blood pressure is a measure of the force
(measured in mmHg) exerted in the lumen of
the blood vessels.
Blood flow is the amount of blood which is
actually reaching the end organs
(tissues of the body).
Resistance is the sum of
many factors which
oppose the flow of blood.
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Pressure, Flow, And Resistance Cardiovascular homeostasis is mainly
dependent on blood flow… but blood flow is
hard to measure.
• Clinically, we check blood pressure
because it is easier to measure, and it is
related to blood flow.
• The relationship between blood flow, blood
pressure, and peripheral resistance follows a
simple formula called Ohms Law.BP = Flow x Resistance
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Pressure, Flow, And Resistance In an effort to meet physiological demands, we
can increase blood flow by:
• Increasing BP
• Decreasing systemic vascular
resistance in the blood vessels
Usually our body will do both –
when we exercise, for example.
figure adapted from http://www.learnhemodynamics.com/hemo/ba
sics.htm
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Pressure, Flow, And Resistance As we have already seen, peripheral resistance
is itself dependent on other factors like the
viscosity of blood, the length of all the blood
vessels in the body (body size), and the
diameter of a vessel.
The first two of these factors (viscosity and the
length of blood vessels) are unchangeable
from moment to moment.
• The diameter, however, is readily adjusted if
the body needs to change blood flow to a
certain capillary bed.
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Pressure, Flow, And Resistance
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Pressure, Flow, And Resistance Example: If the diameter of a blood vessel
decreases by one-half, its resistance to blood
flow increases 16 times!
• “Hardening of the arteries” (loss of elasticity)
seriously hampers the body’s
ability to increase
blood flow to meet
metabolic demands.
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Autoregulation Homeostasis in the body
tissues requires the
cardiovascular system to adjust
pressure and resistance to
maintain adequate blood flow
to vital organs at all times – a
process called
autoregulation.
Autoregulation is controlled
through negative feedback
loops.
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Autoregulation of blood pressure and blood
flow is a complex interplay between:
• The vascular system
• The nervous system
• The endocrine hormones and
organs like the adrenal gland
and the kidney
• The heart
Autoregulation
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Autoregulation The vascular system senses alterations of BP
and blood flow and signals the cardiovascular
centers in the brain.
• The heart then appropriately
modifies its rate and force
of contraction.
• Arterioles and the precapillary
sphincters of the metarterioles
adjust resistance at specific
tissue beds.
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Autoregulation Two of the most important control points are
the pressure receptors (called baroreceptors)
located in the arch of the aorta and the carotid
sinus. There are also baroreceptors in the kidney and
the walls of the heart.
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Autoregulation Stimulation of the baroreceptors in the carotid sinus is called
the carotid sinus reflex , and it helps normalize blood
pressure in the brain.
Another type of sensory receptor important to the process of
autoregulation of BP are the chemoreceptors.
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Autoregulation Chemoreceptors are found in the carotid
bodies (located close to baroreceptors of
carotid sinus) and aortic bodies (located in
the aortic arch).
When they detect hypoxia (low O2),
hypercapnia (high CO2), or acidosis (high H+),
they signal the cardiovascular centers.
• They increase sympathetic stimulation
increasing heart rate and respiratory rate,
and vasoconstricting the vessels (arterioles
and veins) to increase BP.
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Autoregulation The Renin-angiotensin-aldosterone (RAA)
system is an important endocrine component
of autoregulation.
• Renin is released by kidneys when blood
volume falls or blood flow decreases.
• It is subsequently converted into the active
hormone angiotensin II which raises BP
by vasoconstriction and by stimulating
secretion of aldosterone from the
adrenal glands.
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Autoregulation Epinephrine and norepinephrine are also
released from the adrenal medulla as an
endocrine autoregulatory response to
sympathetic stimulation.
• They increase cardiac output by increasing
rate and force of heart contractions.
Antidiuretic hormone (ADH) is released from
the posterior pituitary gland in response to
dehydration or decreased blood volume.
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Autoregulation Atrial Naturetic Peptide (ANP) is a natural
diuretic polypeptide hormone released by cells
of the cardiac atria.
• ANP participates in autoregulation by:
Lowering blood pressure (it causes a direct
vasodilation)
Reducing blood volume (by promoting loss
of salt and water as urine)
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Circulation In an autoregulatory response, important
differences exist between the pulmonary and
systemic circulations:
• Systemic blood vessel walls dilate in
response to hypoxia (low O2) or acidosis to
increase blood flow.
• The walls of the pulmonary blood vessels
constrict to a hypoxic or acidosis stimulus
to ensure that most blood flow is diverted to
better ventilated areas of the lung.
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Circulation A measure of peripheral circulation can be done
by checking the pulse. The pulse is a result of
the alternate expansion and recoil of elastic
arteries after each systole.
• It is strongest in arteries closest to the heart
and becomes weaker further out.
• Normally the pulse
is the same as
the heart rate.
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Circulation Blood pressure is the pressure in arteries
generated by the left ventricle during systole
and the pressure remaining in the arteries
when the ventricle is in diastole.
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Alterations Of Blood Pressure About 50 million Americans have hypertension
(HTN).
• It is the most common disorder
affecting the CV system
and is a major cause of
atherosclerotic vascular
disease (ASVD), heart
failure, kidney disease
and stroke.
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Alterations Of Blood Pressure Hypertension is defined as an elevated
systolic blood
pressure (SBP), an elevated diastolic blood
pressure (DBP), or both. Depending on
severity, it is classified as pre-hypertension,
Stage 1 HTN, or stage 2 HTN.
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Alterations Of Blood Pressure Hypotension is defined as any blood pressure
too low to allow sufficient blood flow (hypo-
perfusion) to meet the body's metabolic
demands (to maintain homeostasis).
Many persons, especially some thin, young
women, have very low BP, yet experience no
dizziness, fatigue, or other symptoms – they
are not hypotensive, and in fact are probably
very healthy (cardiovascular wise).
Hypotension leading to hypo-perfusion
(pressure and flow are related) of critical
organs results in shock
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Shock And Homeostasis The 4 basic types of shock are:
• Hypovolemic shock, due to decreased
blood volume
• Cardiogenic shock, due to poor heart
function
• Obstructive shock, due to obstruction of
blood flow
• Vascular shock, due to excess vasodilation -
as seen in cases of a massive allergy
(anaphylaxis) or sepsis. In the U.S., septic
shock causes >100,000 deaths/yr. and is the
most common cause of death in hospital
critical care units.
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Shock and Homeostasis
Heart rate & force increase Vasoconstriction or vasodilation
depending on type of shock ADH released conserve water Renin released Angiotensin II Aldosterone released
conserve Na+ ANP inhibited
The body responds via negative feedback to restore homeostasis
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Shock And Homeostasis
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Circulatory Routes Blood vessels are organized into circulatory
routes that carry blood to specific parts of the
body.
• The pulmonary circulation leaves the right
heart to allow blood to be re-oxygenated and
to off-load CO2.
• The systemic circulation leaves the left
side of the heart to supply the coronary,
cerebral, renal, digestive and hepatic
circulations (among others). The bronchial
circulation provides oxygenated blood to the
lungs, not the pulmonary circulation, which
oxygenates blood!
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Systemic Circulation - Arteries Aorta (one)
Brachiocephalic (one)
Common Carotid
External Carotid
Internal Carotid
Subclavian
Axillary
Brachial
Radial
Ulnar
Bronchial (usually
3)
Renal
Iliac (common,
internal, external)
Femoral
Popliteal
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Systemic Circulation - Arteries
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Systemic Circulation - Arteries
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Systemic Circulation - Arteries
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Systemic Circulation - Arteries
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Systemic Circulation - Veins
Vena Cava
Brachiocephalic
(two)
External Jugular
Internal Jugular
Subclavian
Axillary
Brachial
Median Cubital
Iliac (common,
internal,
external)
Femoral
Popliteal
Saphenous
Hepatic portal
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Systemic Circulation - Veins
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Systemic Circulation - Veins
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Systemic Circulation - Veins
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Systemic Circulation - Veins
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Portal Circulation The hepatic portal system is designed to
take nutrient- rich venous blood from the
digestive tract capillaries, and transport it to
the sinusoidal capillaries of the liver.
• As it percolates through the liver sinusoids,
the hepatocytes of the liver, acting as the
chemical factories of the body, extract and
add what they wish to maintain homeostasis
(extracting sugars, fats, proteins when
appropriate and then dumping them back
into the circulation when necessary).
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Portal Circulation
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Fetal Circulation The fetus has special circulatory requirements
because their lungs, kidneys and GI tract are
non-functional.
The fetus derives its oxygen and
nutrients and eliminates wastes
through the maternal blood supply
by way of the placenta. Normally,
there is no maternal/fetal mixing;
the fetus is totally dependant on
capillary exchange.
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Oxygenated blood leaves the placenta through
the umbilical vein. It then bypasses the liver
via the ductus venosus and dumps into the
inferior vena cava en route to the right heart.
This oxygen-rich blood then
bypasses the lungs by
traveling to the left heart
through the foramen ovale.
Fetal Circulation
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Blood remaining in the right heart that
manages to flow through the right ventricle
meets with very high resistance from the
closed and soggy lungs.
This blood is diverted into the
left-sided circulation by passing
through the ductus
arteriosus before returning
to the placenta via the
umbilical arteries.
Fetal Circulation
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Fetal circulation (before birth)
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Neonatal Circulation After Birth At birth, the neonate’s lungs open and in just a
few seconds, there is a massive drop in
pulmonary vascular resistance.
• Blood now entering the right heart now sees
lower pressure looking into the lungs and has
no “incentive” to flow through the foremen
ovale or the ductus arteriosus.
Another change also occurs very rapidly - the
umbilical cord is severed.
• And so begins the adult pattern of blood flow.
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Neonatal Circulation After Birth Within hours, days, or weeks after birth, the
umbilical vein atrophies to become the
ligamentum teres.
• The ductus venosus atrophies to become the
ligamentum venosum.
• The foramen ovale becomes the closed fossa
ovale.
• The ductus arteriosus atrophies to become
the ligamentum arteriosum.
• Umbilical arteries atrophy to become the
medial umbilical ligaments.
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Neonatal Circulation After Birth
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Chapter 22
The Lymphatic System and
Immunity
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The Lymphatic System A system consisting of lymphatic vessels
through which a clear fluid (lymph) passes
The major functions of the lymphatic system
include:
• Draining interstitial fluid
• Transporting dietary lipids absorbed by the
gastrointestinal tract to the blood
• Facilitating the immune responses
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The Lymphatic System Components of the lymphatic
system include:
• Lymphatic capillaries
• Lymphatic vessels
• Lymph nodes
• Lymphatic trunks
• Lymphatic ducts
• Primary lymphatic organs
• Secondary lymphatic organs
and tissues
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Lymphatic Vessels and Fluid Lymph is a clear to milky fluid in the
extracellular fluid compartment. Extracellular
fluids include:
• Plasma – the liquid component of blood
• Interstitial fluid – the clear fluid filtered
through capillary walls when it enters the
“interstitium” (space between cells, also called
the intracellular space)
• Lymphatic fluid – the unaltered interstitial
fluid that enters the lymphatic vessels. In the
GI tract, lymphatic fluids also include absorbed
dietary lipids.
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Lymphatic Vessels and Fluid The flow of lymph fluid is always from the
periphery towards the central vasculature.
• It starts as interstitial fluid.
• Then enters lymphatic
capillaries.
• It travels in lymphatic
vessels to the regional
lymph nodes…
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Lymphatic Vessels and Fluid The flow of lymph fluid continued…
• Lymph ascends or descends to the thorax,
either to the Left or Right Lymphatic Duct.
• Lymph fluid’s final destination is the
bloodstream, as it enters through the
Subclavian veins.
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Lymphatic Vessels and Fluid Lymphatic capillaries are slightly larger than
blood capillaries and have a unique one-way
structure.
• The ends of endothelial cells overlap and
permit interstitial fluid to flow in, but not out.
• Anchoring filaments pull openings wider when
interstitial fluid accumulates.
There are specialized lymphatic capillaries
called lacteals that take up dietary lipids in the
small intestine.
Chyle is the name of this “lymph with
lipids”.
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Lymphatic Vessels and Fluid
Lymphatic capillaries showing blind ends and one way flow
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Lymphatic capillaries unite to form larger
lymphatic vessels which resemble veins in
structure but have thinner walls and more
valves.
Lymphatic vessels pass
through lymph nodes –
encapsulated organs with
masses of B and T cells.
• Function as lymph filters
Lymphatic Vessels and Fluid
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Lymphatic Vessels and Fluid
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Lymphatic fluid is moved by pressure in the
interstitial space and the milking action of
skeletal muscle contractions and respiratory
movements.
• An obstruction or
malfunction of lymph
flow leads to edema
from fluid
accumulation in
interstitial spaces.
Lymphatic Vessels and Fluid
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Lymphatic Organs The lymphatic system is
composed of a number of
primary and secondary
organs and tissues widely
distributed throughout
the body - all with the
purpose
of facilitating the immune
response.
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Lymphatic Organs Primary lymph organs are the bone marrow
and thymus.
• Sites where stem cells divide and become
immunocompetent (capable of
mounting an immune response)
Secondary lymphatic organs are
sites where most immune responses
occur, including the spleen and
lymph nodes, and other lymphoid
tissues such as the tonsils.
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Lymphatic Organs Thymus
• The outer cortex is composed of a large
number of immature T cells which migrate
from their birth-place in red bone marrow .
They proliferate and begin to mature with
the help of Dendritic cells (derived from
monocytes) and specialized epithelial cells
(help educate T cells through positive
selection) – only about 25% survive.
• The inner medulla is composed of more
mature T cells.
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Lymphatic Organs The thymus slightly protrudes from the
mediastinum into the lower neck.
• It is a palpable 70g
in infants, atrophies
by puberty, and is
scarcely distinguishable
from surrounding fatty
tissue by old age.
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Lymphatic Organs There are about 600 lymph nodes scattered
along lymphatic vessels (in superficial and deep
groups) that serve as filters to trap and
destroy
foreign objects in lymph fluid.
Important group of regional
lymph nodes include:
• Submandibular
• Cervical
• Axillary
• Mediastinal
• Inguinal
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Lymph fluid enters the node through afferent
vessels and is directed towards the central
medullary sinuses.
Efferent vessels convey
lymph, antibodies and
activated T cells out of
the node at an indentation
called the hilum.
Lymphatic Organs
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The spleen is the body’s largest mass of
lymphatic tissue.
The parenchyma of the organ consists of:
• White pulp - lymphatic tissue where
lymphocytes and macrophages carry out
immune function
• Red pulp – blood-filled venous sinuses where
platelets are stored and
old red cells
are destroyed
Lymphatic Organs
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Lymphatic Organs
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The Immune Response Our immune response includes innate and
adaptive responses:
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Innate Immunity The innate immune response is present at
birth. It is non-specific and non-adaptive.
• It includes our first
line of external,
physical, and
chemical barriers
provided by the
skin and mucous
membranes.
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Innate Immunity Our nonspecific innate
immune response also
includes various
internal defenses
such as antimicrobial
substances, natural
killer cells, phagocytes,
inflammation, and
fever.
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Innate Immunity Internal defenses:
• Phagocytes
Wandering and
fixed macrophages
• Natural killer (NK) cells
• Endogenous antimicrobials
• Complement system
• Iron-binding proteins
• Interferon
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Innate Immunity Phagocytosis is a non-specific process wherein
neutrophils and macrophages (from monocytes)
migrate to an infected area. There are 5 steps:
• Chemotaxis
• Adherence
• Ingestion
• Digestion
• Killing
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Innate Immunity
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Innate Immunity Fever is an abnormally high body temperature
due to resetting of the hypothalamic
thermostat.
• Non-specific response:
speeds up body reactions
increases the effects of endogenous
antimicrobials
sequesters nutrients from microbes
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Innate Immunity Inflammation is defensive response of almost
all body tissues to damage of any kind
(infection, burns, cuts, etc.).
• The four characteristic signs and symptoms of
inflammation are redness, pain, heat, and
swelling.
• It is a non-specific attempt to dispose of
microbes and foreign materials, dilute toxins,
and prepare for healing.
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Innate Immunity The inflammatory response has three basic
stages:
• Vasodilation and increased permeability
• Emigration (movement) of
phagocytes from the
blood into the
interstitial space
and then to site
of damage
• Tissue repair
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Innate Immunity Vasodilation allows more blood to flow to the
damaged area which helps remove toxins and
debris.
• Increased permeability permits entrance of
defensive proteins (antibodies and clotting
factors) to site of injury
Other inflammatory mediators include
histamine, kinins, prostaglandins (PGs),
leukotrienes (LTs), and complement.
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Innate Immunity Emigration of phagocytes depends on
chemotaxis
• Neutrophils predominate in early stages but
die off quickly.
• Monocytes transform into macrophages and
become more potent phagocytes than
neutrophils.
Pus is a mass of dead phagocytes and
damaged tissue.
Pus formation occurs in most inflammatory
responses and usually continues until the
infection subside.
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Innate Immunity The inflammatory response is depicted in this
graphic:
• Edema results from
increased permeability
of blood vessels.
• Pain is a prime symptom
which results from
sensitization of nerve
endings by the
inflammatory chemicals.
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Adaptive Immunity Substances recognized as foreign that provoke
an immune response are called antigens (Ag).
Adaptive immunity describes the ability of the
body to adapt defenses against the antigens of
specific bacteria,
viruses, foreign tissues…
even toxins (think of the
snake handler who
becomes immune to the
venom of snake bites).
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Adaptive Immunity Two properties distinguish between adaptive
immunity and innate immunity:
1. Specificity for foreign molecules which act as
Ag
this involves distinguishing self-molecules
(normal, not antigenic) from nonself
molecules
2. Memory for previously
encountered Ag
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Not all foreign substances are antigenic: We
don’t make antibodies to glass, for example.
Molecules, or parts of molecules tend to be
antigenic if they are:
• Foreign – not ourselves
• Organic
• Structurally complex (proteins are usually
complex and form many of the most potent
antigens)
• Large (high molecular weight)
Adaptive Immunity
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Antigens can have multiple antigenic
determinants called epitopes.
• Each epitope is capable of producing
an immune response.
Entire microbes may act as an
antigen, but typically just
certain small parts (epitopes) of
a large antigen complex triggers
a response.
Antigens can have multiple antigenic determinants called epitopes. Each epitope is capable of producing an immune
response.
Adaptive Immunity
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Adaptive Immunity The adaptive immune response cannot get
started without the aid of the nonspecific
phagocytosis that occurs in the innate immune
response.
• The phagocytic cells that initiate the process
are called antigen presenting cells.
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Antigen-presenting cells (APCs) are mostly
dendritic cells and macrophages, and they
link the innate immune system
and the adaptive immune system.
• Dendritic cells are usually found
in tissues in contact with the
external environment, and they
are the most potent of the
antigen-presenting cell types.
Dendritic cells grow branched projections called dendrites that give the cell its name. However, these do not have any special relation with neurons which possess similar appendages
Adaptive Immunity
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Adaptive Immunity As an antigen-presenting cell engulfs and
destroys a foreign invader, it isolates
the antigens those cells
“display”.
The APC then presents the foreign
Ag to a specific T lymphocyte
called a helper T cell
(also known as a CD4 cell) .
Processed Agis presented
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Adaptive Immunity Once stimulated by antigen
presentation, helper T cells
become activated.
Activated helper T cells are
capable of activating other
lymphocytes to become T
cytotoxic cells (CD8 cells)
which directly kill foreign
invaders and B cells (which
make antibodies that kill or
helps kill foreign invaders).
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Adaptive Immunity Activated B and T cells form the two arms of the
adaptive immune response: Antibody-
mediated immunity and Cell-mediated
immunity.
Helper T cells aid
in both types, and
both types work
together to form
specific bodily
defenses. The Innate and Adaptive Immune systems are depicted
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Adaptive Immunity Cell-mediated immunity involves the production
of cytotoxic T cells that directly attack
invading pathogens (foreign invaders with Ag
harmful to us – particularly intracellular
pathogens and some cancer cells).
• Suppressor and memory T cells are also
produced. Antibody-mediated immunity involves the
production of B cells that transform into
antibody making plasma cells.
• Antibodies (Ab) circulate in extracellular fluids.
• B memory cells are also produced.
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Adaptive Immunity B-cells can be activated
by direct recognition of
antigen through B-cell
receptors or through T-
helper cell activation.
• Activated B-cells undergo
clonal selection to become
antibody producing plasma
cells.
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Adaptive Immunity
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MHC Molecules Our immune system has the remarkable ability,
and responsibility, of responding appropriately
to a wide variety of potential pathogens in our
environment.
• The proteins that are used as cell-markers to
“flag” self from non-self are called MHC
molecules, and are coded for by a group of
genes called the major histocompatibility
complex (MHC).
MHC genes are diverse, and vary greatly
from individual to individual.
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MHC Molecules There are two general classes of MHC
molecules, and at least one or the other, or
both, are found on the surface of all nucleated
cells in the body.
• Class I molecules (MHC-I) are built into
almost all body cells and are used to present
non-self proteins (from bacteria or viruses, for
example) to cytotoxic T cells.
• Class II molecules (MHC-II) are only found
only on APCs.
Both classes are important for antigen
processing and presentation.
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MHC Molecules When APCs come across foreign antigens, they are
broken down and loaded onto MHC-II molecules of
APCs.
The Class II MHC molecules on the APCs present the
fragments to helper T cells, which stimulate an
immune reaction from other cells.
• Clones of activated T cells (and the antibodies
from plasma cells) are now “competent” to
recognize similar antigenic fragments displayed
by infected cells throughout the body and respond
harshly.
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MHC Molecules Infected body cells present antigens using
MHC-1 molecules
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MHC Molecules Cytotoxic T cell
destruction of an
infected cell by release
of perforins that cause
cytolysis
Microbes are destroyed
by granulysin.
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Clonal Selection Clonal selection is the process by which a
lymphocyte proliferates and differentiates in
response to a specific antigen.
• A clone is a population of identical cells, all
recognizing the same antigen as the original cell. Lymphocytes undergo clonal selection to produce:
• Effector cells (the active helper T cells, active
cytotoxic T cells, and plasma cells) that die after
the immune response.
• Memory cells that do not participate in the initial
immune response but are able to respond to a
subsequent exposure - proliferating and
differentiating into more effector and memory
cells.
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Cytokines Cytokines are chemical signals from one cell
that influences another cell.
• They are small protein hormones that control
cell growth and differentiation:
Interferon
Interleukins
Erythropoietin
Tumor necrosis factor
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Copyright © John Wiley & Sons, Inc. All rights reserved.
Antibodies Antibodies (also called immunoglobulins or Igs)
are produced by plasma cells through antibody-
mediated immunity.
• Antibodies are composed of 4 peptide chains:
Two heavy chains and two light chains
• Disulfide bonds link the chains together in a Y-
shaped arrangement.
• The variable region (antigen-binding region)
gives an antibody its specificity.
• The stem is similar for each class of antibody.
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Antibodies Single-Unit antibody structure
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Antibodies Some of the ways antibodies are effective
include:
• Neutralizing a bacterial or viral antibody, or a
toxin by covering the binding sites and causing
agglutination and precipitation (making what
was soluble, insoluble)
• Activating the classical
complement pathway
• Enhancing phagocytosis -
a process called
opsonization
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Antibodies The complement system is a series of blood
proteins that often work in conjunction with
antibodies – it can be activated by multiple
pathways in a step-wise or cascading fashion. It
encourages vasodilation and inflammation,
antigen opsonization,
and antigen
destruction.
The main proteins
are C1-C9.
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A membrane attack complex (MAC) forms as a
result of activation of
the complement
cascade.
• The MAC
results in
lysis of the cell.
Antibodies
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Antibodies There are 5 classes of antibodies:
• IgG – a monomer with two antigen-binding sites
Comprises 80% of total antibody
Only class able to cross the placenta
Provides long-term immunity
• IgM – a pentamer with ten antigen-binding sites
It is a great activator of complement, but has a
short-lived response.
It is the first antibody to appear in an immune
response
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Antibodies Classes of Antibodies
• IgA – a dimer with four antigen-binding sites
prevalent in body secretions like sweat,
tears, saliva, breast milk and gastrointestinal
fluids
• IgE – a monomer involved in allergic reactions
comprises less than 0.1% of total antibody in
the blood
• IgD – a monomer with a wide array of
functions, some of which have been a puzzle
since its discovery in 1964
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Antibodies
Classes of Antibodies
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Antibodies Thousands of memory cells exist after initial
encounter with an antigen - this is called
Immunological Memory.
• With the next appearance of the same
antigen, memory cells can proliferate and
differentiate within hours.
This graphic shows that
serum antibody titers
are much higher and
much faster on the
second response
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Gaining Immunocompetence Within the framework of innate and adaptive
immunity we have discussed, there are a
number of designations for the ways we can
become immunocompetent:
• “Natural Immunity” is not gained through
the tools of modern medicine, whereas
”Artificial Immunity” is.
• Active Immunity refers to the body’s
response to make antibody after exposure to a
pathogen (antigen).
• In Passive Immunity, the body simply
receives antibodies that have been preformed. Active immunity is long-term; passive is
short-term.
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Gaining Immunocompetence Examples
• Natural active – contracting hepatitis A and
production of anti-hepatitis A antibodies
• Natural passive - a baby receives antibodies
from its mother through the placenta and
breast milk.
• Artificial active - a person receives a vaccine
of an attenuated (changed/weakened)
pathogen that stimulates the body to form an
antibody.
• Artificial passive – an injection of prepared
antibody
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Immunological Surveillance A current theory purports that the formation of
cancer cells is a common occurrence in all of us,
and that the immune system continually
recognizes and removes them.
• There are a number of well-recognized tumor
antigens which are displayed on certain
cancerous cells.
These cells are targeted for destruction by
cytotoxic T cells, macrophages and natural
killer cells.
• Most effective in eliminating tumor cells due to
cancer-causing viruses
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The Immune System and Aging Atrophy of the thymus gland results in decreased
T-helper cell populations, and a diminished
mediation of the specific-immune response.
• There is a resulting decreased B-cell response
and decreased number of T-cytotoxic cells.
Compromised immune function with age
results in increased titers of autoantibodies and
an increased incidence of cancer (both
contribute to overall mortality rates.)