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Chapter 43
The Immune System
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Pathogens
 Pathogens are viruses and other
organisms that invade the body and
cause disease.
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Surface Proteins
 The surfaces of the pathogens that
enter the body contain proteins that are
recognized by our body’s defenses.
 These are called antigens.
 Antigens are recognized as foreign and
stimulate an immune response.
 Antigens usually stimulate the production
of antibodies by the immune system.
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Protection From Invaders
 Your body has a variety of mechanisms
to protect it from invasion.
 1. The skin
 2. Mucous
 3. Ciliated lining of the trachea
 4. Internal cellular and chemical defenses
via phagocytes
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2 Major Types of Defense
 1. Innate immunity
 2. Acquired immunity
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1. Innate Immunity
 This type of immunity is present before
any exposure to pathogens and is
available at birth.
 Innate responses help slow the spread
of microbes before the body can build
acquired, specific responses.
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2. Acquired Immunity
 This immunity develops after exposure
to foreign substances.
 Acquired defenses are highly specific.
 They have the ability to distinguish
between very closely related inducing
agents.
 Specificity is achieved by lymphocytes.
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1. The Skin--Innate
 The skin secretes oils and sweat.
 It has a normal pH of 3 to 5 which
prevents colonization of bacteria on the
skin.
 Secretions from the skin also contain
lysozyme which digest the cell walls of
many bacteria.
 It is found in tears, mucous, saliva, etc.
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2. & 3. Mucous and Cilia-Innate
 Mucous often traps
invaders and cilia sweeps
them out of the trachea.
They are either
swallowed where they
usually fall victim to the
low pH of the stomach.
 They may also be
expectorated.
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4. Internal DefensesPhagocytes--Innate
 Phagocytes are certain types of WBC’s
that produce antimicrobial proteins.
 Help initiate inflammation.
 This helps limit the spread of microbes in
the body.
 Non phagocytic WBC’s are called natural
killer cells.
 These play a key role in innate defenses.
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4. Internal DefensesPhagocytes
 Phagocytes bind to the
surfaces of invading cells.
 They use surface
receptors to recognize
structures found on
microorganisms, but not
normal body cells.
 After binding the invader,
the phagocyte engulfs the
invader, forms a vacuole,
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and fuses with a
Lysosomes
 There are 2 ways lysosomes work:
 1. They poison the invader.
 NO and other toxic forms of O2 are made in the
lysosome.
 2. Lysozyme and other enzymes degrade
invader components.
 Some microbes make substances that
allow them to go unnoticed against the
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Natural Killer Cells
 NK cells patrol the body
and attack virus
infected body cells and
cancer cells.
 They recognize surface
proteins and act to
release chemicals into
the cell triggering
apoptosis.
 Not 100% effective.
A human natural killer cell is shown conjugated to a tumor cell. The accumulation of actin
filaments (blue) and CD2 (red) at the immunologic synapse can be seen preceding the
localization of the cytolytic molecule perforin (green).
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 Physical injury or
pathogens can cause
tissue damage and
localized swelling.
 Numerous chemical
signals are released.
 The most active one is
histamine which comes
from mast cells.
Tissue Damage
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Histamine
 Triggers dilation and increased permeability
of capillaries.
 Activated macrophages and other cells
discharge other signals, such as
prostaglandins.
 Prostaglandins promote more blood flow to
the injury site.
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The Injury Site
 The swelling and increased heat are
critical to innate defense.
 They deliver the necessary components
to the site of injury (clotting factor and
antimicrobial protein).
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Blood Clotting
 To plug a wound, the human body has
a system in place that works together
to try to stop blood loss.
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Blood Clotting
 When a person is wounded, substances
are released that stimulate the
production of thrombin from
prothrombin.
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Blood Clotting
 Thrombin is an enzyme that then
catalyzes the formation of fibrin from
fibrinogen.
 Fibrinogen is a protein that is always
circulating in the bloodstream.
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Blood Clotting
 Fibrin is a fibrous protein that captures
red blood cells and stops the flow of
blood.
 When the blood is stopped at the
wound site, it starts to coagulate.
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Blood Clotting
 Coagulation captures platelets that
send out sticky extensions that cling to
other features of the wound.
 Over time, the platelets contract and
the liquid portion of the blood is forced
out of the wound and a scab begins to
form.
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Antigens
 Antigens are foreign molecules that are
recognized by lymphocytes and elicit a
response from them.
 Lymphocytes bind to the epitope on an
antigen.
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2. Acquired ImmunityLymphocytes
 Lymphocytes produce 2 main types of
immune responses:
 1. Humoral response
 Circulating antibodies produced by Blymphocytes
 2. Cell mediated response
 Antibodies produced by T-lymphocytes
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1. The Humoral Response
 Occurs when cells derived from Blymphocytes become activated and
secrete defensive proteins called
antibodies.
 Secreted antibodies accumulate in the
blood and lymph.
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1. The Humoral Response
 Antibodies identify and bind to
microbes and mark them for
elimination.
 Clonal selection is also involved.
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Clonal Selection
 The antibody-driven cloning of T & B
lymphocytes is called clonal-selection
and is fundamental to acquired
immunity.
 When antigens bind to specific
receptors, a small fraction of the body’s
lymphocytes are activated.
 This stimulates the production of
thousands of clones that work to
eliminate an antigen.
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Primary Immune Response
 The primary immune response is the
first time exposure to an antigen.
 Proliferation of lymphocytes occurs.
 The individual may become sick.
 Eventually antibodies clear the antigen
from the system.
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Secondary Immune Response
 The 2° immune response occurs if an
individual is exposed to an antigen
again.
 It is an example of immunological memory.
 It depends on long lived T and B
memory cells.
 They elicit a quick and specific response to
the antigen.
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Lymphocytes
 Lymphocytes are WBCs that mediate
the immune responses.
 There are two main types of
lymphocytes:
 1. B-cells
 2. T-cells
 They are concentrated in the spleen,
lymph nodes, and other lymphoid
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tissues.
Lymphocytes
 Lymphocytes act to recognize antigens
by a means of antigen specific receptors
embedded in their membrane.
 They stimulate production of T & B cells.
 A single T or B cell has about 100,000
antigen-receptors.
 All of them are the same on a particular
cell--they recognize the same epitope.
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Lymphocytes
 Lymphocytes are derived from
pluripotent stem cells in the bone
marrow.
 Each lymphocyte displays specificity for a
particular epitope on an antigen
 It defends against that antigen and other
closely related antigens.
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1. B-Cell Lymphocytes
 Originate and mature in the
bone marrow.
 B-cell chains are anchored into
a membrane of the B-cell.
 They are sometimes called
membrane antibodies or
membrane immunoglobulins.
 B-cells recognize intact
antigens.
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B-Cell Receptors
 B-cell receptors for antigens are Y-shaped.
 They contain 4 polypeptide chains
 2 heavy chains and 2 light chains.
 V regions are variable, their aa sequence varies
extensively from one B-cell to the next.
 C regions are constant and have little variability
in their sequence.
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1. B-Cell Lymphocytes
 B-cells help with
presenting antigens
to helper T-cells in
the course of the
humoral response.
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Immunoglobulins
 Immunoglobins are called Ig’s
 They are structurally very similar to B-cell
receptors.
 They are made by B-lymphocytes (B-cells)
in large quantities.
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Immunoglobulins
 There are 5 main classes.
 IgA
 IgM
 IgG
 IgD
 IgE
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IgA
 Found in serum, saliva, tears, breast
milk, and mucous secretions.
 Neutralizes viruses and bacteria as they
enter the body.
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IgM
 Found in blood and lymph.
 First antibody produced following
infection or immunization.
 Has numerous binding sites.
 Activates compliment-part of innate
system.
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IgG
 It is the main Ig in blood, lymph and
tissue fluid.
 It neutralizes microorganisms, viruses,
and bacterial toxins by binding to them.
 Promotes engulfment by macrophages.
 Activates compliment-part of innate
system.
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IgD
 Found on the surface of antibody
secreting B-cells.
 Found in low concentrations.
 Works with IgM as an antigen receptor.
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IgE
 Found in low concentrations in serum
and connective tissues.
 Plays a crucial role in allergic reactions.
 Binds to mast cells causing a histamine
release in response to an antigen.
 The histamines produce all of the
symptoms associated with allergies:
 Swelling, redness, runny nose and eyes.
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The Complement System
 The complement system comprises part
of the innate defense.
 It becomes activated as a result of the
humoral system (IgG, IgM).
 Numerous inactive serum proteins.
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The Complement System
 Infected cells secrete numerous types
of proteins as a part of the Compliment
System.
 They quickly become active and lyse
foreign invaders when detected.
 Example:  and  interferon.
Interferon
 There are 2 main types ( and ) which
provide innate defense against viral
infection.
 They act to stimulate neighboring cells to
produce substances to prevent further
infection.
 This is the body’s way of preventing the
spread of the infection.
Membrane Attack Complex
 The MAC is triggered by substances
from the body’s innate defenses.
 MAC is triggered by the antigen-antibody
response.
 This complex forms pores in the
membrane, and they allow H2O and ions to
rush in and lyse an infected cell.
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MHC
 Major histocompatibility complex genes
code for MHC molecules.
 When MHC molecules are synthesized,
they get transported to the plasma
membrane.
 On the way, they bind with fragments of
antigen protein within a cell and bring it to
the surface.
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MHC
 MHC is what is called antigen presentation.
 Due to antigen presentation, nearby T-cells can
recognize the fragment on the cell surface and
act accordingly.
 MHC proteins are very polymorphic.
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Foreign Antigens
 There are 2 ways foreign antigens end up
inside cells of the body. Their source
determines which MHC molecule gets
used and which T-cell assists in its
removal.
 1. Foreign antigens synthesized within the
cell (viruses, cancer).
 2. Foreign materials can become
internalized by phagocytosis
or endocytosis
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Class I MHC Molecules
 These are found on most nucleated
cells in body.
 They bind antigens synthesized within the
cell.
 Infected cells and cancerous cells display such
antigens.
 Cytotoxic T-cells destroy cells displaying
Class I MHC molecules.
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Class II MHC Molecules
 Class II MHC molecules are made by
only a few types of cells-dendritic cells,
macrophages, and B-cells.
 These bind peptides derived from foreign
materials that have been fragmented and
internalized.
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Class II MHC Molecules
 Class II MHC molecules display these
antigens to helper T-cells.
 Helper T cells alert nearby B-cells and
cytotoxic T cells by secreting cytokines.
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Immunoglobulin Gene
Rearrangement
 There are many different types of B-cell
and T-cell antibodies.
 This is due to the random nature of the
recombinase enzyme.
 It can create a number of different gene
products which are the B-cell (or T-cell)
antigen receptors.
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B-Cell & T-Cell Activation
 When B-cells and T-cells become
activated by antigens, they are
stimulated to divide many times.
 2 clones of daughter cells are created.
 1 is short lived, antibody secreting cell.
 The other is a memory cell that is long
lived and bears receptors for the same
antigen.
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B-Cell Activation
 Many antigens recognized by B-cells
contain multiple epitopes.
 Exposure to a single antigen can
stimulate a variety of different B-cells.
 This gives rise to a clone of thousands of
plasma cells (effector and memory).
 These clones secrete antibodies specific to
the epitope that provoked their production.
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B-Cell Activation
 Activated B-cells secrete antibodies that
have a Y-shaped antigen-binding
structure, but no transmembrane
region.
 These binding sites are responsible for
identifying specific antigens.
 Identification of antigens facilitates their
removal.
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2. The Cell Mediated
Response
 When the cell mediated response and
clonal selection occurs:
 Cytotoxic lymphocytes directly destroy
infected body cells, cancer cells, or foreign
tissue.
 There are 2 main types of T-cells
 1. Helper T-cells
 2. Cytotoxic T-cells
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2. T-Cell Lymphocytes
 T-cell lymphocytes originate in the bone
marrow and mature in the thymus.
 They consist of 2 polypeptide chains,  & .
 They, too, are linked into a cell’s plasma
membrane.
 They also have V and C regions.
 T-cells recognize fragments of antigens that
are bound to normal cell-surface proteins
called MHC molecules.
Helper T-Cells
 Helper T-cells are central to the
network of cellular interactions.
 They respond to peptide antigens
displayed on antigen presenting cells.
 They stimulate activation of B-cells and
cytotoxic T-cells.
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Helper T-Cells
 When helper T-cells encounter a class II
MHC molecule-antigen complex, they
stimulate the production of clones of
helper T-cells and memory helper T-cells.
 This promotes the removal of infected
cells.
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Helper T-Cells
 Helper T-cells secrete many different
cytokines (signals) to stimulate other
lymphocytes.
 This promotes humoral and cell mediated
responses.
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Cytotoxic T-Cells
 When activated, cytotoxic T-cells secrete
proteins which destroy the infected cell.
 Circulating antibodies then mark the
exposed pathogens for disposal.
 Cytotoxic T-cells are the effectors.
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Ways to Prevent Infection
 There are 2 types of immunization:
 1. Active immunity
 2. Passive immunity
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1. Active Immunity
 This is immunity conferred by a natural
exposure to an infectious agent.
 It also can develop following
immunization.
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2. Passive Immunity
 Passive immunity results from the
transfer of antibodies from an immune
individual to someone who isn’t.
 Transferred antibodies are immediately
available to attack antigens to which
they are specific.
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Edward Jenner
 English physician in the late 1700’s.
 Noticed that milkmaids who had
contracted cowpox were resistant to
smallpox.
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Edward Jenner
 Jenner took fluid from a cowpox sore
and scratched the arm of a healthy
farmboy with it.
 When the boy was later exposed to
smallpox, he was immune.
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Monoclonal Antibody
Production
 Monoclonal antibodies are large
quantities of a single type of antibody
made to a specific antigen.
 They are derived from a single B-cell
clone.
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Monoclonal Antibodies:
Production
 mAb production begins when an animal
is injected with the desired antigen and
then produces a specific plasma cell.
 The animal’s plasma cells are then
removed and fused with immortal
tumor cell lines such as He La cells.
 This results in the production of what is
known as a hybridoma.
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Monoclonal Antibodies
 The hybridoma, which can now divide
endlessly, synthesizes vast quantities of
the specific antibody which can be used
for diagnostic and treatment purposes.
 These antibodies can be isolated and
purified and given to sick individuals.
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Monoclonal Antibodies
 Use: Emergency treatment of rabies.
 An individual sick with rabies is given mAb
made specific to the virus.
 The mAb bind to the virus and are
collected by the cells of the immune
system.
 The body’s immune system is allowed to
catch up and eventually the person gets
better.
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Monoclonal Antibodies
 Other uses: Diagnosis of malarial
infection, pregnancy testing, HIV, heart
attack, etc.
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Allergies
 These are exaggerated responses to
certain antigens.
 The most common allergies involve
antibodies of the IgE class.
 When plasma cells secrete IgE antibodies
specific for antigens on the surface of
pollen grains, hay fever results.
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Allergies
 Some antibodies are attached to mast
cells which are found in connective
tissue.
 When allergens enter the body, they
become attached to the mast cell-IgE
association.
 This triggers the release of histamine
and other inflammatory substances.
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Allergies
 Histamine causes dilation and increased
permeability of small blood vessels.
 This causes the common symptoms of
allergy responses.
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