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Biology
Sylvia S. Mader
Michael Windelspecht
Chapter 33
The Lymphatic and
Immune Systems
Lecture Outline
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Outline
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33.1 Evolution of Immune Systems
33.2 The Lymphatic System
33.3 Innate Immune Defenses
33.4 Adaptive Immune Defenses
33.5 Immune System Disorders and
Adverse Reactions
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Foods and Anaphylactic Shock
• Seemingly harmless items or foods may pose a
threat to some people.
– Upon contact with these items, individuals may develop
a life-threatening condition known as anaphylactic
shock, which if not treated, can result in loss of
consciousness and even death.
– These strong allergic reactions illustrate the power of the
immune system, harmful in some, but not most cases.
• Our immune system protects us against viruses,
bacteria, fungi, parasites, and environmental toxins.
33.1 Evolution of Immune Systems
• Immune System
– Protects from bacterial and viral pathogens, toxins, even cancerous cells
• Immunity in Cellular Slime Molds
– Composed of many individual amoeboid cells living in unison as a “slug”
– Sentinel cells – circulate throughout the slug and engulf bacteria and
toxins
• Eventually remove themselves from the body of the slug
• Immunity in Drosophila
– Contain cellular receptors capable of recognizing common components
of pathogenic microbes
•
•
•
•
Pathogen-associated molecular patterns (PAMPs)
Trigger an immune reaction
Receptors for PAMPs found in diverse organisms.
May have been one of earliest cellular receptors that evolved for pathogen
recognition
• Both immunities illustrate a type of defense known as
innate immunity.
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Evolution of Immune Systems
• The Rise of Adaptive Immunity
– Innate immunity
• Recognizes microbial invaders quickly, but shows no
signs of an increased response upon repeated exposure
– Adaptive immunity
• Results in the production of receptors on surface of white
blood cells that bind to a foreign antigen
– Stimulates lymphocytes to increase in number, resulting in an
increased response to specific antigens and immunological
memory
– Originally developed in an ancestor that gave rise to the jawed
vertebrates
» Precise mechanism causing adaptive immunity in ancestor
not known
» Likely involved insertion of transposon or “jumping gene” into
a gene coding for an antigen receptor similar to receptor for
PAMPs
» Gene rearrangement is involved
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33.2 The Lymphatic System
• Lymphatic System
– Consists of lymphatic vessels and the lymphatic organs
– Three main homeostatic functions:
• Lymphatic capillaries take up and return excess fluid to the
bloodstream.
• Lacteals absorb fats in the form of lipoproteins and transport
them to the bloodstream.
• Lymphatic system produces, maintains, and distributes
lymphocytes.
– Lymphocytes resist infection and disease by responding to
» Invading pathogens such as bacteria or viruses
» Abnormal body cells such as cancer cells
» Foreign proteins such as toxins
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The Lymphatic System
• Lymphatic Vessels
– One-way system that begins with lymphatic
capillaries
• Tiny, closed-ended vessels found throughout the body
• Take up excess tissue fluid (interstitial)
• Lymph – fluid located within lymphatic capillaries
– Lymph flows one way
» From a capillary to ever-larger lymphatic vessels
» Finally to a lymphatic duct, which returns lymph to a
subclavian vein
» Backflow is prevented by one-way valves
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Lymphatic System
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Tonsils: aggregates of lymphoid tissue that respond to pathogens
in the pharynx
Right lymphatic duct:
empties lymph into the
right subclavian vein
Left subclavian vein: transports blood away from the left arm and
the left ventral chest wall toward the heart
Red bone marrow: site for the origin of all types of blood cells
Right subclavian vein:
transports blood away from the
right arm and the right ventral
chest wall toward the h eart
Thymus: lymphoid organ where T cells mature
Axillary lymph nodes:
located in the underarm region
Thoracic duct: empties
lymph into the left
subclavian vein
Spleen: resident T cells and B cells respond to the presence of
antigen in blood
tissue
fluid
lymphatic
capillary
Inguinal lymph nodes:
located in the groin region
tissue cell
blood
capillary
valve
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The Lymphatic System
• Lymphoid (Lymphatic) Organs
– Red Bone Marrow
• Site of origin for all types of blood cells
• Site of maturation for B cells
– Thymus Gland
• Located between the trachea and the sternum in the
upper thoracic cavity
• Site of maturation for T cells
– T cells migrate to thymus from red bone marrow.
• T cells learn to recognize combinations of self and foreign
molecules.
– Mature T cells in bloodstream encounter foreign molecules or
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cells and proliferate and become activated.
The Lymphatic System
• Lymphoid Organs (cont’d)
– Lymph Nodes
• The capsule surrounds two distinct regions, cortex
and medulla.
• Macrophages concentrated in medulla cleanse
lymph.
• Macrophages “present” debris or pathogens to T
cells in lymph node.
• B and T cells in lymph nodes help destroy
pathogens.
• Lymph nodes are named for their location.
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The Lymphatic System
• Lymphoid Organs (cont’d):
– Spleen
• It is located in upper left side of the abdominal cavity just posterior to
the stomach.
• Macrophages remove old and defective blood cells.
• Red pulp filters and cleanses blood.
– Tonsils
• Patches of lymphatic tissue are located in the pharynx.
• They prevent entry of pathogens through the nose and mouth.
– Peyer patches
• Located in intestinal wall
—Vermiform appendix
• Attached to cecum
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The Lymphatic Organs
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33.3 Innate Immune Defenses
• Immunity
– The capability of removing or killing foreign substances,
pathogens, and cancer cells from the body.
• Innate Defenses
–
–
–
–
Do not distinguish one type of threat from another
Are fully functional without previous exposure to invaders
Occur immediately or shortly after infection occurs
Types of innate immune defenses:
•
•
•
•
Physical and chemical barriers to entry
Inflammatory response
Phagocytes and natural killer cells
Protective proteins such as complement and interferons
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Overview of Innate Immune Defenses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Innate defenses
Barriers
to entry
skin and
mucous
membranes
Protective
proteins
Phagocytes and
natural killer cells
Inflammatory
response
dendritic
cell
pathogens
antimicrobial
molecules
macrophage
cytokines
neutrophil
monocyte
complement proteins
and interferons
in plasma
natural
killer cells
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Innate Immune Defenses
• Physical and Chemical Barriers
– Skin and mucous membranes lining the respiratory,
digestive, and urinary tracts
– Cilia lining the respiratory tract sweep mucus and
particles into the throat
– Antimicrobial molecules in secretions of oil glands,
mucous membranes, and the stomach
• Lysozyme, in mucus, an enzyme that lyses bacteria
• Acidic pH of stomach kills microbes
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Innate Immune Defenses
• Inflammatory Response
– Localized tissue response to injury
– Damaged cells and mast cells release histamine which
causes capillaries to dilate and become more permeable.
– Enlarged capillaries cause skin to redden.
– Swelling stimulates free nerve endings, causing pain.
– Neutrophils and monocytes migrate to the site of
injury.
• Monocytes differentiate into macrophages.
• Macrophages release colony-stimulating factors,
stimulating production and release of white blood cells.
• Neutrophils, dendritic cells, and macrophages
phagocytose pathogens.
– Acute-phase proteins, released by the liver in response to
inflammatory mediators, make it easier for phagocytes to
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engulf invaders.
Inflammatory Response
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Skin
2. Resident macrophages and dendritic
cells phagocytize pathogens and
release cytokines, which stimulate
the inflammatory response.
Tissue
mast cell
macrophage
neutrophil
cytokines
monocyte
histamine
1. Injured tissue cells and mast cells
release histamine and other chemical
mediators, which cause capillaries
to dilate and increase blood flow.
injured tissue
pathogen
dendritic
cell
blood clot
Capillary
4. Blood clotting walls off
capillary and prevents
blood loss.
3. Neutrophils and monocytes (become
macrophages) squeeze through the
capillary wall and phagocytize
pathogens.
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Macrophage Engulfing
Bacteria
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
cytoplasmic
extension from
macrophage
bacteria
SEM 1,075×
© Dennis Kunkel/Phototake
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Innate Immune Defenses
• Fever
– Maintenance of an elevated body temperature
– In some instances, a fever may be beneficial.
• It’s the body’s way of informing us that something
is wrong.
• Certain bacteria or viruses may not survive as well
at higher temperatures.
• Some immune mechanisms work better at higher
body temperatures.
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Innate Immune Defenses
• Phagocytes and Natural Killer (NK) Cells
– Neutrophils
• Leave the bloodstream and phagocytize bacteria
• Release antimicrobial peptides and bacteria-digesting enzymes
• Generate free radicals which kill engulfed bacteria
– Eosinophils
• Phagocytic cells
• Also mount an attack against parasites that are too large to be consumed via
phagocytosis
– Macrophages and dendritic cells
• Engulf and destroy pathogens
• Stimulate T cells in lymph nodes, which initiate adaptive immune responses
– Natural killer (NK) cells
• Large, granular lymphocytes
• Kill virus-infected cells and cancer cells by cell-to-cell contact
• Virus-infected cells, lacking a self molecule (MHC-1) may be recognized and
killed.
• Numbers don’t increase after stimulation, like lymphocytes.
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Innate Immune Defenses
• Protective Proteins
– Complement
• A collection of plasma proteins that “complement”
certain immune responses
• Must be activated by pathogens
• Helps to destroy pathogens in three ways
– Enhanced inflammation
– Bind to pathogens coated with antibodies to ensure
phagocytosis
– Form a membrane attack complex that produces holes in
the surface of some bacteria and viruses
– Fluids entering bacterial cell or virus cause bursting.
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Innate Immune Defenses
• Protective Proteins
– Interferons
• Cytokines that affect the behavior of other
cells
• Produced by virus-infected cells
• Bind to receptors of non-infected cells
– Causes them to produce substances that interfere
with viral replication
• Used to treat certain cancers and viral
infections, such as hepatitis C
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Action of the Complement System
Against a Bacterium
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complement proteins
membrane
attack complex
Complement proteins
form a donutlike ring,
called a membrane
attack complex, in the
plasma membrane.
Fluid and salts enter
susceptible cells
through the membrane
attack complex.
fluids
and
salts
Lysis of the cell results
in its destruction.
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33.4 Adaptive Immune Defenses
• Also known as acquired immunity
– Because adaptive defenses are not inborn
• Take 5–7 days to become activated but last
for years
• Involve three steps
– Recognition of an antigen
– Response to the antigen
– Memory of the antigen
• An antigen is any substance that
stimulates the immune system to react.
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Adaptive Immune Defenses
• Lymphocytes
– Are capable of “recognizing” and binding to
specific antigens
– Have antigen receptors on their plasma
membrane
– The receptor protein’s shape allows it to
combine with a specific antigen.
– Pathogens, cancer cells, and transplanted
tissues and organs bear antigens the immune
system recognizes as nonself.
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Adaptive Immune Defenses
• Adaptive immunity is primarily the result of
– B cells
• B-cell receptors bind directly to antigens.
• B cells give rise to plasma cells.
• Plasma cells produce and secrete antibodies.
– T cells
• T-cell receptors bind to antigens presented by
antigen-presenting cells.
• Helper T cells regulate specific immunity.
• Cytotoxic T cells kill virus-infected cells and
cancer cells.
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Overview of Adaptive Immune Defenses
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
memory
B cell
B cell
antibody
Antibodymediated
immunity
plasma
cell
BCR
APC
antigen
TCR
memory
TH cell
Adaptive
defenses
activated
TH cell
TH cell
activated
TC cell
Cellmediated
immunity
antigen
memory
TC cell
virus-infected
cell
TC cell
TCR
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Adaptive Immune Defenses
• Antibody-Mediated Immunity
• Clonal selection theory:
– The antigen selects which lymphocyte will
• Undergo clonal expansion
• Produce more lymphocytes
– Most of the cloned lymphocytes become plasma
cells that produce specific antibodies.
– Some of the cloned lymphocytes become memory
B cells.
• If the same antigen enters the system again, memory B
cells quickly divide and give rise to more lymphocytes
capable of quickly producing antibodies.
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Clonal Selection
Theory as It
Applies to B
Cells
B-cell
receptor
(BCR)
B cell
antigens
cytokines from T cells
Activation
1
Clonal expansion
3
2
antibody
Memory B cells
Plasma cells
Apoptosis
Apoptosis
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Structure of Antibodies
• Antibodies (immunoglobulins)
• Consist of two heavy and two light polypeptide chains
in a Y shape
• Both types of chains have variable and constant regions.
• Neutralize pathogens by coating their antigens,
preventing them from binding to receptors on cells
• Attract white blood cells that move in for the kill
• Immune complexes may be engulfed by neutrophils or
macrophages or may activate the complement system.
• Class is determined by the structure of the antibody’s
constant region.
•
•
•
•
IgG – Main type of antibody in circulation
IgA – Main type secreted in milk, tears, and saliva
IgM – The first antibodies produced; also indicate infection
IgE – Bound to receptors on eosinophils and mast cells in
tissues
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Structure of Antibodies
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antigen
antigen-binding
sites
antigen binds
to binding site
light
chain
C
C
heavy
chain
C = constant
V = variable
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Adaptive Immune Defenses
• Monoclonal Antibodies
• Antibodies against a specific antigen
• All of the same type
• In vitro (outside the body in the laboratory)
production of monoclonal antibodies
– B cells are removed from an animal and exposed
to a particular antigen.
– The resulting plasma cells are fused with myeloma
cells (malignant plasma cells that live and divide
indefinitely).
– The fused cells (hybridomas) secrete the
monoclonal antibody.
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Adaptive Immune Defenses
• Medical Uses for Monoclonal Antibodies
– To make quick and certain diagnoses of various
conditions
– Used to signify pregnancy by detecting a particular
hormone (hCG) in the urine of a pregnant woman
– Promise as potential drugs to help fight disease
• RSV, a common virus that causes serious respiratory
tract infections in very young children, is being treated
with a monoclonal antibody drug.
• Since the first therapeutic monoclonal antibody was
approved by the FDA in 1986, over 20 are now available
and hundreds more are being tested.
– Adalimumab (Humira) binds to and inhibits tumor necrosis factor
and is used to treat several autoimmune diseases.
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Adaptive Immune Defenses
• T-Cells and Cell-Mediated Immunity
– T-cells receptor (TCR) recognizes antigens
displayed by antigen-presenting cells (APCs).
• Antigen is first linked to a major histocompatibility
complex (MHC) protein in the plasma membrane of the
APC.
– After the TCR binds to the antigen, the T cell
undergoes clonal expansion.
– After the immune response has been successful,
most of the T cells undergo apoptosis.
– Some T cells remain as memory T cells.
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Adaptive Immune Defenses
• Types of T Cells
• Cytotoxic T Cells
– Destroy antigen-bearing cells
– Contain storage vacuoles containing perforins and
granzymes
• Helper T Cells
– Activate other T cells and B cells
– Regulate immunity by secreting cytokines (signaling
molecules)
• Memory T cells
– Persist after a successful immune response
– Provide protection if the same antigen is encountered again
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Clonal Selection
Theory as It
Applies to T Cells
T-cell receptor (TCR)
TC cell
Binding to
MHC-I + antigen
Dendritic
cell
1
cytokines
MHC-I
viral
antigen
Cytotoxic
T cell
virus-infected
cell
Activation and
clonal expansion
2
Death by
apoptosis
3
Apoptosis
4
Memory
T cell
36
Cell-Mediated Immunity
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cytotoxic T cell
antigen fragment
MHC-I
target cell
(virus-infected
or cancer cell)
cytotoxic
T cell
Cytotoxic T cell
vesicle
granzyme
perforin
Perforin
forms hole
in target cell.
Target cell
a.
target cell
Granzymes
enter through the
hole and cause
target cell to
undergo apoptosis.
b.
SEM 1,250X
(b): © Steve Gschmeissner/Photo Researchers, Inc.
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Adaptive Immune Defenses
• HIV Infections
– The primary host for HIV is a helper T cell.
• The host (helper T cell) produces viruses that go
on to destroy more helper T cells.
• At first an individual is able to stay ahead of the
virus by producing enough helper T cells.
• Gradually, the HIV count rises and the helper Tcell count drops.
• Affected patients become susceptible to
opportunistic infections.
– Characteristic of an AIDS diagnosis
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AIDS and Opportunistic
Infections
39
Progression of HIV Infection
During Its Three Stages
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107
Category A: Acute Phase
Category B: Chronic Phase
Category C: AIDS
HIV count in
blood peaks.
1000
106
900
Helper T-cell
count crashes and
then gradually
declines.
800
700
105
Person now
has AIDS.
600
500
104
HIV count in blood
rises dramatically.
400
HIV per ml Plasma
Helper T-cell Count in Blood (cells/mm3)
1100
300
103
HIV count crashes
due to immune
system activity.
200
100
helper T cell
HIV
102
0
1
1 – 2 months
2
3
4
5
6
7
8
9
10
11
Years Since Infection
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Adaptive Immune Defenses
• Cytokines as Therapeutic Agents
– Cytokine
• Soluble protein that acts as a signaling molecule
• Cytokines called interleukins are produced by white blood
cells.
– Stimulate other white blood cells
– Interleukins might awaken the immune system and lead to the
destruction of the cancer.
» IL-2 is being used to treat some forms of melanoma and kidney cancer.
• Tumor necrosis factor (TNF) is a cytokine produced by
macrophages.
– Promotes the inflammatory response
– Causes the death of cancer cells
• Anti-TNF monoclonal antibodies are being developed as
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potential treatments for inflammatory diseases.
Adaptive Immune Defenses
• Active Immunity
– It occurs when an individual produces his/her
own immune response against an antigen.
– Immunization
• It involves use of vaccines, substances that
contain an antigen to which the immune system
responds.
• Pathogens or pathogen products treated to remove
virulence are introduced to the patient via a
vaccine.
• It is dependent upon memory B cells and memory
T cells capable of responding to lower doses of
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antigen.
Antibody Titers
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Adaptive Immune Defenses
• Passive Immunity
– Occurs when an individual receives another
person’s antibodies (immunoglobulins) or immune
cells to combat a disease
• Short-lived
• Newborns are often passively immune since antibodies
have crossed the placenta from the mother’s blood.
– Breast-feeding prolongs natural, passive immunity.
– May be used to prevent illness in a patient who has
been exposed to certain infectious agents or toxins.
―Examples: Rabies, tetanus, botulism, snake bites
– Cells of the immune system may be transferred to
a patient in the case of a bone marrow transplant. 44
Passive
Immunity
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© Digital Vision/Getty Images
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33.5 Immune System Disorders and
Adverse Reactions
• Immunodeficiencies
– They result in some degree of increased
susceptibility to infection.
– Primary immunodeficiencies are genetic, passed
from parents to offspring.
– Severe Combined Immune Deficiency (SCID)
• Neither T nor B cells function
• By about 3 months of age, when most of the antibodies
an infant has obtained from the mother have been
degraded, untreated SCID infants die.
– Possible treatments include a bone marrow transplant.
– X-Linked Agammaglobulinemia (XLA)
• Caused by mutation in a gene on the X chromosome
necessary for proper development of B cells
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Immune System Disorders
and Adverse Reactions
• Allergies
– Hypersensitivities to substances that ordinarily
would not harm the body
• Immediate allergic response
– IgE antibodies
– Causes release of histamine, which brings about the
symptoms of the allergy
– Individuals with asthma have difficulty breathing and
wheezing.
– Anaphylactic shock – occurs after the allergen has entered
the bloodstream.
» Life-threatening
• Delayed allergic response
– Memory T cells regulated by influence of cytokines
47
An Allergic Reaction
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allergen
histamine and other
chemicals
B cell
IgE
antibodies
plasma cell
IgE receptor
mast cell
© Damien Lovegrove/SPL/Photo Researchers, Inc.
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Immune System Disorders and
Adverse Reactions
• Autoimmune Disease
– Cytotoxic T cells or antibodies mistakenly attack the
body’s own cells or molecules.
– There appears to be a genetic tendency to develop
autoimmune diseases.
– Immune system fails to distinguish between self and
nonself antigens.
– Certain antigens of microbial pathogens can
resemble host antigens (molecular mimicry).
– Examples of autoimmune diseases:
• Rheumatoid arthritis (inflammation in synovial joints)
• Myasthenia gravis
• Systemic lupus erythematosus (lupus)
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Rheumatoid Arthritis
51
Systemic Lupus
52
Immune System Disorders and Adverse
Reactions
• Transplant Rejection
– Antibodies and cytotoxic T cells cause destruction
of transplanted foreign tissues in the body.
• Immune system is correctly distinguishing between self
and nonself antigens.
• Xenotransplantation
– It is the transplantation of animal tissues and organs
into humans.
• Potential way to solve human donor organ shortage
• Genetic engineering makes animal organs less antigenic
by removing MHC antigens.
• Tissue Engineering
– Production of human organs from stem cells may
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eliminate rejection problem.