Chapter 21&22

Copyright © John Wiley & Sons, Inc. All rights reserved.
Chapter 21
Blood Vessels
and
Hemodynamics

 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

 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

 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.

 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.

 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.

 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.

 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.

 The body contains three
types of capillaries:
• Continuous capillaries
• Fenestrated capillaries
• Sinusoids

•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.

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.

 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

 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.

 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.

 Fluid that is not reabsorbed (about 3L/ day for the entire
body) enters the lymphatic vessels to be eventually
returned to
the blood.

GasAnd Nutrient Exchange

 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

 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

Proximal
valve
Distal
valve
1
Proximal
valve
Distal
valve
1 2
Proximal
valve
Distal
valve
1 2 3

 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

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.

 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

 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/basics.htm

 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.



 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.

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.

 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

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

 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.

 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

ShockAnd 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.

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

ShockAnd Homeostasis

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!

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

Systemic
Circulation
-Arteries

Systemic Circulation -Arteries

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

Systemic
Circulation
- Veins

Systemic Circulation - Veins

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).

Portal Circulation

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.

 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

 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

Fetal circulation (before birth)

Neonatal CirculationAfter 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.

 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.

Chapter 22
The Lymphatic
System and
Immunity

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

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

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.

 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…

 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.

 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”.

Lymphatic capillaries showing blind ends and one way flow

 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 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 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.

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.

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.

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.

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

 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

 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

Lymphatic Organs

The Immune Response
 Our immune response includes innate and adaptive
responses:

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.

Innate Immunity
 Our nonspecific innate
immune response also
includes various internal
defenses such as
antimicrobial substances,
natural killer cells,
phagocytes, inflammation,
and fever.

Innate Immunity
 Internal defenses:
• Phagocytes
 Wandering and
fixed macrophages
• Natural killer (NK) cells
• Endogenous antimicrobials
• Complement system
• Iron-binding proteins
• Interferon

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

Innate Immunity

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

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.

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

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.

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.

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.

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).

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

 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

 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

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.

 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

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 Ag
is presented

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).

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

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.

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.

Adaptive Immunity

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.

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.

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.

MHC Molecules
 Infected body cells present antigens using
MHC-1 molecules

MHC Molecules
 Cytotoxic T cell
destruction of an infected
cell by release of
perforins that cause
cytolysis
 Microbes are destroyed
by granulysin.

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.

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

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.

Antibodies
 Single-Unit antibody structure

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

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.

 A membrane attack complex (MAC) forms as a result of
activation of
the complement
cascade.
• The MAC
results in
lysis of the cell.
Antibodies

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

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

Antibodies
Classes of Antibodies

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

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.

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

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

The Immune System andAging
 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.)

Chapter 21&22

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Chapter 21&22