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Transcript
Chapter 36
Defenses Against Disease
Lecture Outlines by Gregory Ahearn,
University of North Florida
Copyright © 2011 Pearson Education Inc.
Chapter 36 At a Glance
 36.1 What Are the Mechanisms of Defense
Against Disease?
 36.2 How Do Nonspecific Defenses Function?
 36.3 What Are the Key Components of the
Adaptive Immune Response?
 36.4 How Does the Adaptive Immune System
Recognize Invaders?
 36.5 How Does the Adaptive Immune System
Launch an Attack?
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Chapter 36 At a Glance (continued)
 36.6 How Does the Adaptive Immune System
Remember Its Past Victories?
 36.7 How Does Medical Care Assist the
Immune Response?
 36.8 What Happens When the Immune System
Malfunctions?
 36.9 How Does the Immune System Combat
Cancer?
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 The world is teeming with microscopic living organisms
called microbes, which include bacteria, protists, and
fungi; and viruses, which are not considered to be alive
– Most microbes live in water or the soil; most that live in
animal bodies do not harm them and may be beneficial
– When microbes cause disease, they are called
pathogens
– Most microbial diseases, such as cholera, measles,
plague, tetanus, and chicken pox, have been with
humans for thousands of years
– New, more deadly strains of familiar pathogens are
called emerging infectious diseases
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Emerging infectious diseases
– Since the early 1980s, several viruses have emerged as
serious threats to human health, including HIV, Ebola
virus, West Nile virus, SARS, swine flu, and bird flu
– One strain of the common intestinal bacterium E. coli,
which is normally harmless, can cause food poisoning
– Some Staphylococcus bacteria that normally cannot
penetrate the skin will cause severe infections or fatal
toxic shock syndrome when they enter the body
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Vertebrate animals have three major lines of
defense against disease
– Nonspecific external barriers
– Nonspecific internal defenses
– Specific internal defenses
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Levels of Defense Against Disease
Nonspecific External Barriers
skin, mucous membranes
If these barriers are penetrated,
the body responds with
Innate Immune Response
phagocytic and natural killer cells,
inflammation, fever
If the innate immune response is insufficient,
the body responds with
Adaptive Immune Response
cell-mediated immunity, humoral immunity
Biology: Life on Earth, 9e
Fig. 36-1
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Vertebrate animals have three major lines of defense
against disease (continued)
– Nonspecific external barriers
– These barriers prevent most disease-causing
microbes from entering the body
– They are primarily anatomical structures, such as skin
and cilia, and secretions such as tears, saliva, and
mucus
– These barriers cover the external surfaces of the body
and line the body cavities that come in contact with
the external environment such as the surfaces of the
respiratory, digestive, and urogenital tracts
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Vertebrate animals have three major lines of defense
against disease (continued)
– Nonspecific internal defenses
– If the external barriers are breached, a variety of
nonspecific internal defenses, collectively called the
innate immune response, swing into action
– Components of this response include:
– White blood cells, which engulf foreign particles or
destroy infected cells
– Chemicals released by damaged cells and
proteins released by white blood cells that trigger
inflammation and fever
– These responses operate regardless of the exact nature
of the invader, neutralizing the threat
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Vertebrate animals have three major lines of
defense against disease (continued)
– Specific internal defenses
– The final line of defense is the adaptive immune
response, in which immune cells selectively
destroy specific invading microbes and toxins
and then remember the invader
– This allows for a rapid response to the invader if
it reappears in the future
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Table 36-1
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Table 36-2
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.1 What Are the Mechanisms of Defense Against
Disease?
 Invertebrate animals possess the first two lines of
defense
– Invertebrates lack adaptive immune responses and must
rely on the two nonspecific defenses that include:
– External skeletons
– Slimy secretions
– White blood cells that attack pathogens and secrete
proteins to neutralize the invaders or the toxins they
release
– Defensive proteins, such as lysosome, are similar in
vertebrates and invertebrates, suggesting a common
ancestor among most of today’s animal species
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The ideal defenses are barriers that prevent
invaders from entering the body in the first place
 If these barriers are breached, however, the
body has several nonspecific methods of killing
a wide variety of invading microbes
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The skin and mucous membranes form external
barriers to invasion
– The first line of defense consists of two surfaces
with direct exposure to the environment
–The skin
–The mucous membranes of the digestive,
respiratory, and urogenital tracts
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The skin and its secretions block entry and provide an
inhospitable environment for microbial growth
– The skin is a barrier to microbes
– The outer surface of the skin consists of dry, dead
cells filled with tough proteins that do not allow the
microbes to obtain the water and nutrients they need
to survive
– The secretions from sweat and sebaceous glands
contain natural antibiotics, such as lactic acid, that
inhibit the growth of many bacteria and fungi
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Antimicrobial secretions, mucus, and ciliary action
defend the mucous membranes against microbes
– Mucous membrane secretions trap microbes entering the
nose or mouth
– They contain antibacterial proteins, including lysozyme,
which kills bacteria by digesting their cell walls, and
defensin, which makes holes in bacterial plasma
membranes
– Cilia on the membranes sweep up the mucus, so it is
swallowed or coughed or sneezed out of the body
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
The Protective Function of Mucus
Bacteria trapped
by mucus and cilia
Fig. 36-2
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
– If the microbes are swallowed, they enter the stomach,
where protein-digesting enzymes and extreme acidity is
lethal to them
– The intestines contain bacteria that, while harmless to
humans, secrete substances that destroy invading
bacteria or fungi
– In the urinary tract, the slight acidity of urine inhibits
bacterial growth
– In females, acidic secretions and mucus help protect the
vagina
– Tears, urination, diarrhea, and vomiting all help to expel
invaders
– Despite these defenses, many disease-causing microbes
enter the body through the mucous membranes or
through cuts in the skin
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The innate immune response combats invading
microbes
– Microbes that penetrate the skin or mucous
membranes encounter an array of internal
defenses, collectively called innate immunity
– Innate immune responses are nonspecific—that
is, they attack many different types of microbes
rather than targeting particular invaders
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Innate immune responses fall into three categories:
– White blood cells, which are also called leukocytes,
attack and destroy invading cells or the body’s own cells
if they have been infected by viruses
– The inflammatory response recruits leukocytes to the
site of a wound and walls off the injured area, isolating
the infected tissue from the rest of the body
– Fever is produced when microbes start a major infection
in the body, which both slows down microbial
reproduction and enhances the body’s own fighting
abilities
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Phagocytic leukocytes and natural killer cells destroy
invading microbes
– The body has several types of leukocytes, collectively
known as phagocytes, which ingest foreign invaders
and cellular debris by phagocytosis
– Three important types of phagocytes are:
– Macrophages
– Neutrophils
– Dendritic cells
– These cells travel within the bloodstream, ooze through
capillary walls, and patrol the body’s tissues, where they
consume bacteria and other foreign elements
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
The Attack of the Macrophages
Fig. 36-3
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Phagocytic leukocytes and natural killer cells destroy
invading microbes (continued)
– Natural killer cells are another type of leukocyte, which
strike primarily at the body’s own cells that have become
cancerous or have been invaded by viruses
– The surfaces of normal body cells display proteins of
the major histocompatibility complex (MHC),
identifying the cell as “self”
– Natural killer cells kill any “nonself” cells they
encounter by releasing proteins that bore holes in the
infected or cancerous cell’s membranes and then
secrete enzymes through the holes that kill the
infected cell
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The inflammatory response attracts phagocytes
to injured or infected tissue
– The inflammatory response causes tissues to
become warm, red, swollen, and painful
– This defense mechanism has several functions:
–It attracts phagocytes to infected or injured
tissue
–It promotes blood clotting
–It initiates protective behavior by causing pain
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The inflammatory response begins when
damaged cells release chemicals that cause
certain cells in the connective tissue, called
mast cells, to release histamine
– Histamine relaxes the smooth muscle
surrounding arterioles, increasing blood flow and
causing capillary walls to become leaky
–Extra blood flowing through leaky capillaries
drives fluid from the blood and into the
wounded area, causing redness, warmth, and
swelling
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 The inflammatory response (continued)
– Other chemicals released by the wounded cells, mast
cells, and by the microbes themselves attract
macrophages, neutrophils, and dendritic cells
– These cells consume bacteria, dirt, and cellular debris
– In some cases pus, a thick, whitish mixture of dead
bacteria, tissue debris, and white blood cells, may
accumulate
– Other chemicals released by injured cells initiate blood
clotting to reduce blood loss and prevent more microbes
from entering the blood stream
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Author Animation: The Inflammatory Response
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
The Inflammatory Response
dead cell
layer
1 Tissue damage carries
bacteria into the wound
epidermis
2 Wounded cells
release chemicals (red)
that stimulate mast cells
3 Mast cells release
histamine (blue)
dermis
4 Histamine increases capillary
blood flow and permeability
5 Phagocytes leave
the capillaries and ingest
bacteria and dead cells
Fig. 36-4
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Fever combats large-scale infections
– If invaders breach these defenses and mount a full-blown
infection, they may trigger a fever, which is an important
part of the body’s defense against infection
– The human thermostat, located in the hypothalamus
of the brain, is set at 97–99ºF
– During an infection, macrophages release a protein
called endogenous pyrogen that travels to the
hypothalamus and raises the thermostat’s set point
– Elevated body temperature increases phagocytic
activity and slows bacterial reproduction
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.2 How Do Nonspecific Defenses Function?
 Fever combats large-scale infections (continued)
– Fever also stimulates cells infected by viruses to produce
a protein called interferon, which travels to other cells
and increases their resistance to viral attack; interferon
also stimulates natural killer cells that destroy virusinfected body cells
– In an experiment, volunteers were infected with a virus
and given aspirin (to reduce fever) or a placebo
– Those with aspirin had more viruses in their noses
and coughed out more viruses than the controls
because fevers in the controls helped reduce the viral
infection
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 External barriers and the nonspecific defenses—
phagocytic cells, natural killer cells, the inflammatory
response, and fever—may be penetrated by specific
microbes
– When these mechanisms are breached, the body mounts
a highly specific and coordinated adaptive immune
response directed against the particular organism that
successfully colonized the body
– The adaptive immune response attacks one specific type
of microbe, overcomes it, and provides future protection
against that microbe but no others
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 The adaptive immune system consists of cells
and molecules dispersed throughout the body
– The adaptive immune system (or simply the
immune system) is distributed throughout the
body, with concentrations of cells in certain
locations
– It consists of three major components: immune
cells, tissues and organs, and secreted proteins
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 Immune cells
– The adaptive immune response is produced by
interactions among several types of white blood cells,
such as macrophages, dendritic cells, and lymphocytes
– Macrophages and dendritic cells play a role in both
the innate and adaptive immune responses
– The key cellular players in the adaptive immune
response are B cells and T cells, which arise from
stem cells in the bone marrow
– Some of the stem cells complete their
development in the bone marrow, becoming B (for
bone) cells
– Others migrate from the marrow to the thymus,
where they develop into T (for thymus) cells
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 Tissues and organs
– The cells of the immune system are produced
and reside in a variety of locations, including the
vessels of the lymphatic system, the lymph
nodes, the thymus, the spleen, and patches of
specialized connective tissue such as the tonsils
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 Tissues and organs (continued)
– Lymph flows through the lymph nodes, which
contain masses of macrophages and specialized
white blood cells called lymphocytes
– The thymus is located beneath the breastbone,
slightly above the heart, and is essential for
development of some immune cells
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 Tissues and organs (continued)
– The spleen, located in the abdominal cavity, is a
fist-sized organ that filters blood, exposing it to
white blood cells that destroy foreign particles
and aged red blood cells
– The tonsils are located in the throat and contain
macrophages and other white blood cells that
sample microbes entering the body through the
mouth, destroying many of them and often
starting an adaptive immune response
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
The Lymphatic System Contains Much of the
Immune System
thymus
thoracic duct
bone marrow
spleen
lymph vessels
lymph nodes
valve prevents
backflow
lymph node
chambers packed
with white blood cells
Biology: Life on Earth, 9e
Fig. 36-5
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 Secreted proteins
– Leukocytes and some other cells secrete many different
proteins, collectively called cytokines, that are used for
communication between cells
– A large number of proteins in the blood, collectively
called complement, assist the immune system in killing
invading microbes
– Some cytokines and complement proteins are
involved in both the innate and adaptive responses
– A subset of leukocytes, called B cells, produce antibodies
that help the immune system recognize invading
microbes and destroy them
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.3 What Are the Key Components of the Adaptive
Immune System?
 All adaptive immune responses include the
same three steps:
1. Lymphocytes recognize an invading microbe
and distinguish the invader from self
2. They launch an attack
3. They retain a memory of the invader that allows
them to ward off future infections by the same
type of microbe
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 To understand how the immune system
recognizes invaders and initiates a response,
we must answer three related questions:
– How do lymphocytes recognize foreign cells and
molecules?
– How can lymphocytes produce specific
responses to so many different types of cells and
molecules?
– How do they avoid mistaking the body’s own
cells and molecules for invaders?
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 The adaptive immune system recognizes
invaders’ complex molecules
– Bacteria and humans differ from one another
because each contains specific, complex
molecules that the other does not have
– These large, complex molecules are called
antigens, because they are “antibody
generating” molecules that can provoke an
immune response, including the production of
antibodies
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 The adaptive immune system recognizes invaders’
complex molecules (continued)
– Antigens are often located on the surfaces of invading
microbes
– Many viral antigens become incorporated into the plasma
membranes of infected body cells
– Viral or bacterial antigens are also “displayed” on the
plasma membranes of dendritic cells and macrophages
that engulf them
– Other antigens, such as toxins released by bacteria, may
be toxins in the blood plasma, lymph, or other
extracellular fluids
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibodies and T-cell receptors recognize and
bind to foreign antigens
– Lymphocytes generate two types of proteins that
recognize, bind, and help to destroy specific
antigens:
–Antibody proteins, produced by B cells and
their offspring
–T-cell receptor proteins, produced by T cells
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibodies recognize and help destroy invaders
– Antibodies are Y-shaped proteins composed of
two pairs of peptide chains: one pair of identical
large (heavy) chains and one pair of identical
small (light) chains
– Both heavy and light chains consist of a
constant region, which is similar in all
antibodies of the same type, and a variable
region that differs among individual antibodies
– Antibodies have two functional parts: the “arms”
of the Y and the “stem” of the Y
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibodies recognize and help destroy invaders
(continued)
– The variable regions at the arm tips form sites
that bind antigens
– Each binding site has a particular size, shape,
and electrical charge so that only certain
molecules can fit in and bind to the antibody
– The sites are so specific that each antibody can
bind only a few, very similar, types of antigen
molecules
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Antibody Structure
antigen
light
chain
heavy
chain
Variable regions form
antigen binding sites
Constant regions are
the same in all antibodies
of a given type
Fig. 36-6
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibodies recognize and help destroy invaders
(continued)
– Antibodies may function as receptors, binding to
specific antigens and eliciting a response to
them, or as effectors, helping them destroy cells
or molecules that bear the antigen
–As a receptor, the stem of the antibody
anchors the antibody in the plasma membrane
of the B cell that produced it, while its two
arms stick out from the B cell, sampling the
blood and lymph for antigen molecules
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
– Antibodies (continued)
–When the arm of the antibody encounters an
antigen with a compatible chemical structure,
it binds to it and initiates a response in the B
cell
–As effectors, many antibodies are secreted
into the bloodstream, where they neutralize
poisonous antigens, destroy microbes that
bear antigens, or attract macrophages that
engulf the antigen-bearing microbes
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Antibodies Can Serve as Receptors or Effectors
macrophage
B cell
antibody
antigen
antibody
antigen
(a) Antibody receptor function
(b) Antibody effector function
Fig. 36-7
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 T-cell receptors recognize invaders and help trigger an
immune response
– T-cell receptors are found only on the surfaces of T cells
– Like antibodies, they consist of peptide chains that
form highly specific binding sites for antigens
– Unlike antibodies, T-cell receptors are never released
into the bloodstream, and they do not directly
contribute to the destruction of invading microbes or
toxic molecules
– A T-cell receptor triggers a response in its T cell when the
receptor binds an antigen on a cell that has ingested an
invading microbe
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 The immune system can recognize millions of
different antigens
– The adaptive immune system recognizes and
responds to virtually all of the harmful antigens
that may be encountered, because B and T cells
produce millions of different antibodies and T-cell
receptors
– How can the body produce so many?
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibody genes are assembled from segments of DNA
– There are no genes for entire antibodies
– Instead, B cells have genes that code for parts of
antibodies—constant regions (C), variable regions (V),
and “joining” (J) or “diversity” (D) regions that connect the
two
– The constant region in each chain is the same for any
antibody of a particular type
– Humans have about 200 genes for the variable region
of heavy chains, and 50 and 6 genes, respectively, for
the diversity and joining regions
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibody genes are assembled from segments of DNA
(continued)
– There are 150 genes for the variable region of the light
chain, and 5 genes for the joining region
– As each B cell develops, it randomly cuts out and
discards all but one gene of each type, and assembles
two unique antibody genes from the genes it keeps
– A heavy-chain gene, consisting of one variable, one
diversity, one joining, and one constant region
– A light-chain gene, consisting of one variable, one
joining, and one constant region
– Antibodies are produced from these composite genes
Biology: Life on Earth, 9e
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Recombination Produces Antibody Genes
heavy
chain
V2
V1
V3
light
chain
V4
V200
V2
V1
V3
D1 D2
V4
D50
J1
J1
V150
J2
J2
J3
J4
J6
CM CD CG CE CA
J5
CK
(a) Genes for parts of the heavy chain (top) and light chain (bottom) of antibodies
heavy
chain
V2 D11 J4 CG
light
chain
V80 J2
V87 D8
CK
J1
V101 J5
Cell 1
CG
V111 D40 J1
CK
J1
V6
Cell 2
CG
CK
Cell 3
(b) Complete antibody genes in three different B cells
V2
D11
J4
V80
J2
CK
CG
V80
J2
CK
CG
Cell 1
V87
D8
J1
V101
J5
CK
V101
J5
CK
CG
CG
Cell 2
(c) Antibodies synthesized by these three B cells
Biology: Life on Earth, 9e
V111
D40
J1
V6
J1
CK
CG
V6
J1
CK
CG
Cell 3
Fig. 36-8
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibody genes are assembled from segments of DNA
(continued)
– The random assembly of composite antibody genes
yields about 3 million unique combinations
– Further diversity arises because only part of each joining
region is actually used in any given antibody
– Immunologists estimate that 15 to 20 billion unique
antibodies are possible
– The result is that each B cell produces an antibody that is
different from the one produced by every other B cell,
except its own daughter cells
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibody genes are assembled from segments
of DNA (continued)
– T-cell receptors are made from different genes,
but the process is similar
– There are more parts available for constructing
T-cell receptor genes, so there may be as many
as a quadrillion different possible T-cell
receptors!
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 Antibodies and T-cell receptors are not tailormade for antigens
– B and T cells do not design antibodies and T-cell
receptors to fit invading antigens
– Instead, the immune system randomly
synthesizes millions of different antibodies and Tcell receptors
– Antigens almost always encounter antibodies or
T-cell receptors that will bind them
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 The immune system distinguishes self from non-self
– The surface of body cells bear large proteins and
polysaccharides that are collectively called the major
histocompatibility complex (MHC), which are unique to
each person
– If the cells of the immune system bind to the antigens of
the MHC, they undergo apoptosis, or “programmed cell
death”
– Therefore, the immune system distinguishes self from
non-self by retaining only those immune cells that do not
respond to the body’s own molecules
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.4 How Does the Adaptive Immune System
Recognize Invaders?
 The immune system distinguishes self from non-self
(continued)
– Not all self-reactive B and T cells are eliminated in this
way
– Although no one understands the mechanism,
regulatory T cells prevent these remaining selfreacting lymphocytes from attacking the body and
causing an autoimmune disease
– A person’s MHC proteins act as foreign antigens in
other people’s bodies during organ transplants; a
donor must be found whose MHC proteins are similar
to the recipient in order to reduce effects of the
immune system on the transplanted organ
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.5 How Does the Adaptive Immune System
Launch an Attack?
 The adaptive immune system simultaneously
launches two types of attack against microbial
invaders:
– Humoral immunity is provided by B cells and
the antibodies that they secrete into the blood
that attack pathogens outside the body’s cells
– Cell-mediated immunity is produced by a type
of T cell called the cytotoxic T cell that attacks
infected body cells, killing both the cell and any
pathogens inside it
Biology: Life on Earth, 9e
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 An immune response takes time to develop
– While a person may have millions of different
antibodies and T-cell receptors, there is only one,
or a few, cells bearing each type of antibody or Tcell receptor
– The immune system requires time to be effective
because cells recognizing the invader must
multiply and differentiate
– It takes 1 or 2 weeks to mount a strong immune
response after the first exposure to an invading
microbe
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An Effective Immune Response Takes Time to
Develop
Fig. 36-9
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.5 How Does the Adaptive Immune System
Launch an Attack?
 Humoral immunity is produced by antibodies dissolved
in the blood
– Each B cell bears its own unique antibodies on its
surface
– When an infection occurs, the antibodies borne by a few
B cells can bind to antigens on the invader
– Antigen–antibody binding causes these B cells, but no
others, to divide rapidly by the process of clonal
selection, producing a population of “clones” of the
original cell that was selected after responding to a
particular invading antigen
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 Humoral immunity is produced by antibodies dissolved
in the blood (continued)
– The daughter cells differentiate into two cell types:
– Memory B cells, which do not release antibodies but
play an important role in future immunity to the invader
that stimulated their production
– Plasma cells, which become enlarged and produce a
huge quantity of specific antibodies that are released
into the bloodstream
– Clonal selection, multiplication of activated B cells,
differentiation into memory and plasma cells, and
antibody secretion by plasma cells all take time to
overcome an infection
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Author Animation: B Cell Activation and
Differentiation
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Clonal Selection Among B Cells by Invading
Antigens
antigens
antibodies
1 Invading antigens
bind to antibodies on
one B cell (dark blue)
2 The B cell “selected”
by the antigen multiplies
rapidly
3 A large clone of
genetically identical
B cells is produced
4 These B cells
differentiate into
plasma cells and
memory B cells
plasma cell
5 Plasma cells
release antibodies
into the blood
Biology: Life on Earth, 9e
endoplasmic
reticulum
memory B
cell
antibodies
Fig. 36-10
Copyright © 2011 Pearson Education Inc.
36.5 How Does the Adaptive Immune System
Launch an Attack?
 Humoral antibodies have multiple modes of
action
– Antibodies in the blood combat invading
molecules or microbes in three ways:
1. The circulating antibodies may bind to a
foreign molecule, virus, or cell and render it
harmless by a process called neutralization
– An example of neutralization is an
antibody covering the active site of a toxic
enzyme in snake venom
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Antibodies Neutralize Toxic Molecules
snake
venom
enzyme
active
site
antibody
Antibodies block the
active site of the toxic
enzymes in snake venom
Biology: Life on Earth, 9e
Fig. 36-11
Copyright © 2011 Pearson Education Inc.
36.5 How Does the Adaptive Immune System
Launch an Attack?
 Antibodies in the blood combat invading
molecules or microbes in three ways
(continued)
2. Antibodies may coat the surface of invading
molecules, viruses, or cells and make it
easier for phagocytic cells to destroy them
– Macrophages recognize the antibody
stems sticking out into the blood, then
engulf the antibody-coated invaders and
digest them
Biology: Life on Earth, 9e
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 Antibodies in the blood combat invading
molecules or microbes in three ways
(continued)
3. When antibodies bind to antigens on the
surface of a microbe, the antibodies interact
with complement proteins that are always
present in the blood
– Some of the complement proteins punch
holes in the plasma membranes of the
microbe, killing it
– Other complement proteins promote
phagocytosis of the invaders
Biology: Life on Earth, 9e
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 Humoral immunity fights invaders that are outside cells
– Antibodies are large proteins that cannot enter cells;
therefore, the humoral response is effective only against
bacteria, bacterial toxins, or fungi when they are outside
of cells, in the blood or extracellular fluid
– Viruses are vulnerable when they are outside of body
cells, but after they enter a body cell, they are safe from
antibody attack
– Cell-mediated immune reactions are required to fight
viruses once they have entered body cells
Biology: Life on Earth, 9e
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 Cell-mediated immunity is produced by cytotoxic T cells
– Cell-mediated immunity, produced by cytotoxic T cells, is
the body’s primary defense against cells that are
cancerous or that have been infected by viruses
– Cytotoxic T cells in the blood may bump into an
infected body cell that is displaying a viral protein on
its surface
– The cytotoxic T cell receptor will bind to the viral
protein and squirt proteins onto the surface of the
infected cell, punching holes in the cell and killing it,
sparing new body cells a future infection
– Cancerous cells also display unusual proteins that the
cytotoxic T cells recognize as foreign, and are killed as a
result
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Cell-mediated Immunity in Action
Fig. 36-12
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.5 How Does the Adaptive Immune System
Launch an Attack?
 Helper T cells enhance both humoral and cell-mediated
immune responses
– B cells and cytotoxic T cells are ineffective without
assistance from helper T cells
– Helper T cells bear receptors that bind to antigens
displayed on the surfaces of dendritic cells or
macrophages that have engulfed and digested
invading microbes
– When its receptor binds an antigen, a helper T cell
multiplies rapidly, and its daughter cells differentiate
and release cytokinins that stimulate cell division and
differentiation in both B cells and cytotoxic T cells
Biology: Life on Earth, 9e
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36.5 How Does the Adaptive Immune System
Launch an Attack?
 Helper T cells enhance both humoral and cellmediated immune responses (continued)
– Both B cells and cytotoxic T cells are most
effective against infection when they receive
stimulation by cytokinins from helper T cells
– Human immunodeficiency virus (HIV), which
causes AIDS, kills off helper T cells, and without
these cells, the immune system cannot fight off
diseases that would otherwise be trivial
Biology: Life on Earth, 9e
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A Summary of Humoral and Cell-Mediated
Immune Responses
HUMORAL IMMUNITY
Targets invaders outside cells (e.g.,
viruses, bacteria, fungi, protists, and
toxins)
HELPER T CELLS
CELL-MEDIATED IMMUNITY
Stimulate both humoral and cell-mediated Targets defective body cells (e.g., infected
cells and cancer cells), transplants
immunity by releasing cytokines
virus
viral
antigen
Viral antigens
presented on the
surfaces of
dendritic cells or
macrophages,
and infected cells
dendritic cell
or macrophage
infected cell
B-cell antibodies bind
to viral antigens and
stimulate the B cells to
divide and differentiate
T-cell receptors bind
to viral antigens
antibody
cytokines
B cell
helper T cell
cytotoxic T cell
Cytokines released by
helper T cells stimulate B
cells and cytotoxic T cells
Fig. 36-13, 1 of 2
Biology: Life on Earth, 9e
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A Summary of Humoral and Cell-Mediated
Immune Responses
HUMORAL IMMUNITY
Targets invaders outside cells (e.g.,
viruses, bacteria, fungi, protists, and
toxins)
HELPER T CELLS
CELL-MEDIATED IMMUNITY
Stimulate both humoral and cell-mediated
immunity by releasing cytokines
Targets defective body cells (e.g., infected
cells and cancer cells), transplants
antibody
cytokines
helper T cell
B cell
cytotoxic T cell
Cytokines released by
helper T cells stimulate B
cells and cytotoxic T cells
plasma
cell
memory B cell
memory
helper
T cell
memory
cytotoxic
T cell
cytotoxic T cell
infected
cell
Plasma cells secrete
antibodies into the blood
and extracellular fluid
Memory cells confer
future immunity to this
virus
Cytotoxic T cells release
pore-forming proteins
that destroy infected cells
Fig. 36-13, 2 of 2
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36.6 How Does the Adaptive Immune System
Remember Its Past Victories?
 After recovering from a disease, you remain
immune to that particular microbe for many
years, perhaps a lifetime
– Some of the daughter cells of the original B cells,
cytotoxic T cells, and helper T cells that
responded to the original infection differentiate
into memory B cells and memory T cells that
survive for many years
– If the body is reinvaded by the same type of
microbe, the memory cells recognize the invader
and mount an immune response
Biology: Life on Earth, 9e
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Author Animation: Humoral Versus Cell-Mediated
Immunity
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.6 How Does the Adaptive Immune System
Remember Its Past Victories?
– Memory B cells rapidly produce a clone of plasma cells,
secreting antibodies that combat this second invasion
– Memory T cells produce clones of either helper T cells or
cytotoxic T cells specific for the “remembered” invader
– Each memory cell responds so fast and so largely in a
second infection, the body fends off the attack before the
person suffers any symptoms—they have become
immune
– Acquired immunity confers long-lasting protection against
many diseases such as small pox, measles, mumps, and
chicken pox
Biology: Life on Earth, 9e
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Author Animation: Memory B Cells
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
Acquired Immunity
Fig. 36-14
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.7 How Does Medical Care Assist the Immune
Response?
 Antibiotics slow down microbial reproduction
– Antibiotics are chemicals that help to combat infection
by slowing down the multiplication of bacteria, fungi, or
protists
– The occasional mutant microbe that is resistant to an
antibiotic will pass on the genes for resistance to its
offspring, which results in many antibiotics becoming
ineffective in treating diseases
– Antibiotics are not effective against viruses
– Drugs are available that target different stages of the
viral cycle of infection, and are used to treat HIV,
severe herpes, and in some cases, the flu virus
Biology: Life on Earth, 9e
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36.7 How Does Medical Care Assist the Immune
Response?
 Vaccinations stimulate the development of memory
cells and future immunity against disease
– A vaccine stimulates an immune response by exposing a
person to antigens produced by a pathogen
– Vaccines often consist of weakened or killed
microbes, or some of the pathogen’s antigens
– Exposure to these antigens results in the body
producing an army of memory cells that confer
immunity against living microbes of the same type
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 Allergies are misdirected immune responses
– Allergies are immune reactions to harmless
substances that are treated as if they were
pathogens
–Common allergies include those to pollen,
mold spores, bee or wasp venoms, and some
foods such as milk, eggs, fish, wheat, tree
nuts, and peanuts
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 An allergic reaction
– All allergic reaction begins when allergy-causing
antigens, called allergens, enter the body and
bind to “allergy antibodies” on a special type of B
cell
– This B cell proliferates, producing plasma cells
that pour out allergy antibodies into the plasma
– The antibodies attach to mast cells, mostly in the
respiratory and digestive tracts
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36.8 What Happens When the Immune System
Malfunctions?
 An allergic reaction (continued)
– If allergens later bind to these attached antibodies, they
trigger the release of histamine, which causes leaky
capillaries and other symptoms of inflammation
– In the respiratory tract, histamine increases mucous
secretions and results in symptoms such as a runny
nose, sneezing, and congestion typical of “hay fever”
– Food allergies may cause intestinal cramps and diarrhea;
some reactions are so strong that the airways may
completely close, causing death by suffocation
Biology: Life on Earth, 9e
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An Allergic Reaction to Pollen
1 First exposure to pollen
(yellow) stimulates B cells to
produce “allergy” plasma cells
2 Plasma cells
produce allergy
antibodies
mast
cell
plasma
cell
3 Allergy antibodies
bind to mast cells
4 Reexposure to pollen results
in pollen binding to allergy
antibodies on mast cells
5 Binding of pollen stimulates mast
cells to release histamine (blue),
triggering the inflammatory response
Biology: Life on Earth, 9e
Fig. 36-15
Copyright © 2011 Pearson Education Inc.
36.8 What Happens When the Immune System
Malfunctions?
 An autoimmune disease is an immune response
against the body’s own molecules
– Occasionally, our immune system produces “anti-self”
antibodies
– The result is an autoimmune disease in which the
immune system attacks a component of one’s own body,
such as a type of anemia where antibodies destroy a
person’s red blood cells
– Type 1 diabetes may begin when the immune system
attacks the insulin-secreting cells of the pancreas
– Other autoimmune diseases include rheumatoid arthritis,
multiple sclerosis, and systemic lupus
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 An autoimmune disease is an immune response
against the body’s own molecules (continued)
– There are no known cures for autoimmune diseases
– Replacement therapy can alleviate the symptoms—for
instance, by giving insulin to diabetics or blood
transfusions to anemia victims
– The autoimmune response can be reduced with drugs
that suppress the immune response
– This course of action also reduces responses to the
everyday assaults of disease microbes, so the therapy
has major drawbacks
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 Immune deficiency diseases occur when the body
cannot mount an effective immune response
– There are two very different disorders in which the
immune system cannot combat routine infections:
– Severe combined immune deficiency (SCID), a
group of genetic defects in which few or no immune
cells are formed
– Acquired immune deficiency syndrome (AIDS),
where a viral infection destroys a formerly functional
immune system
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HIV Causes AIDS
Fig. 36-16
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.8 What Happens When the Immune System
Malfunctions?
 Severe combined immune deficiency is an inherited
disorder
– A child with severe combined immune deficiency (SCID)
may survive the first few months of postnatal life,
protected by antibodies acquired from the mother during
pregnancy
– Once these antibodies are lost, common infections can
prove fatal because the child lacking an immune system
cannot generate an effective immune response
– A form of therapy is to transplant bone marrow from a
healthy donor into the child to provide enough immune
cells to confer normal immune responses
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 AIDS is an acquired immune deficiency disease
– The most common immune deficiency disease is
acquired immune deficiency syndrome (AIDS)
– AIDS is caused by human immunodeficiency
viruses (HIV) that undermine the immune system by
infecting and destroying helper T cells, stimulating
both the cell-mediated and humoral immune
responses
– AIDS does not kill people directly, but AIDS victims
become increasingly susceptible to other diseases as
their helper T-cell populations decline
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36.8 What Happens When the Immune System
Malfunctions?
 AIDS is an acquired immune deficiency disease
(continued)
– Because HIV cannot survive for long outside the body, it
is transmitted only by the direct contact of broken skin or
mucous membranes with virus-laden body fluids,
including blood, semen, vaginal secretions, and breast
milk
– HIV can spread by sexual activity, by sharing needles
among intravenous drug users, or through blood
transfusions
– HIV enters a helper T cell and hijacks the cell’s
metabolic machinery, forcing it to make more viruses
which then emerge, taking an outer coating of T-cell
membrane with them
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 AIDS is an acquired immune deficiency disease
(continued)
– Early in the infection, as the immune system
fights the virus, the victim may develop a fever,
rash, muscle aches, headaches, and enlarged
lymph nodes
– Over time, the helper T cell levels drop, severely
weakening the immune response
– As HIV levels increase, they kill more helper T
cells and the person becomes prey to other
infections
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Author Animation: HIV: The AIDS Virus
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.8 What Happens When the Immune System
Malfunctions?
 AIDS is an acquired immune deficiency disease
(continued)
– Several drugs can slow down the replication of
HIV and thereby slow the progress of AIDS;
unfortunately, HIV can mutate into forms that are
resistant to the drugs
– However, some HIV-positive individuals receiving
the best medical care might now live out a
normal life span
Biology: Life on Earth, 9e
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36.8 What Happens When the Immune System
Malfunctions?
 AIDS is an acquired immune deficiency disease
(continued)
– The best solution would be to develop a vaccine against
HIV
– This is a challenge because HIV disables the immune
response that a vaccine depends on
– Furthermore, HIV has an incredibly high mutation rate,
perhaps a thousand times faster than that of flu viruses
– Lone infected individuals may harbor different strains
of HIV in their blood and semen because of mutations
that occurred within their bodies after they were first
infected
– Despite billions of dollars spent to develop a vaccine,
none have proven effective
Biology: Life on Earth, 9e
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36.9 How Does the Immune System Combat
Cancer?
 Cancer will kill more than 500,000 people in the
United States this year
– Approximately 40% of U.S. citizens will
eventually contract some form of cancer
– Cancers may be triggered by many causes,
including environmental factors such as UV
radiation or smoking, faulty genes, mistakes
during cell division, and viruses
– All these triggers produce cancer by sabotaging
the mechanisms that normally control the growth
of the body’s own cells
Biology: Life on Earth, 9e
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36.9 How Does the Immune System Combat
Cancer?
 The immune system recognizes most cancerous cells
as foreign
– Cancer cells are self and the immune response usually
does not respond to self
– However, the process that causes a cell to become
cancerous leads to slightly different proteins appearing
on their surfaces
– Natural killer cells and cytotoxic T cells encounter these
new proteins, recognize them as non-self antigens, and
destroy the cancer cells
– Some cancer cells do not bear antigens that allow the
immune system to recognize them as foreign or, as in
leukemia, suppress the immune system
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.9 How Does the Immune System Combat
Cancer?
 Vaccination can prevent some cancers
– Some cancers are caused by viruses, including some
cancers of the liver, mouth, throat, and penis; some types
of leukemia; and probably all cervical cancers
– In the United States, two vaccines are available that help
prevent certain cancers:
– A vaccine against hepatitis B, which reduces the risk
of liver cancer
– A vaccine against two human papilloma viruses, which
cause most cases of cervical cancer
Biology: Life on Earth, 9e
Copyright © 2011 Pearson Education Inc.
36.9 How Does the Immune System Combat
Cancer?
 Vaccines may someday help to cure cancer (continued)
– Some “treatment vaccines” may cure certain cancers by
providing a patient with antigens commonly found on
cells of the type of cancer that the patient has, often
enhanced in various ways to boost the patient’s immune
response against the cancer
– Current trials of this type of vaccine against prostate
cancer and melanoma (a type of skin cancer) are in
progress
– Other treatment vaccines consist of antigens from a
patient’s own tumor cells, often enhanced to stimulate
a stronger immune response
Biology: Life on Earth, 9e
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36.9 How Does the Immune System Combat
Cancer?
 Vaccines may someday help to cure cancer
(continued)
– Still another approach is to take antigenpresenting dendritic cells from a patient, expose
them to antigens from cancer cells, and force
them to multiply rapidly in culture
– The resulting daughter cells are then injected
back into the patient
– This large number of activated dendritic cells
should stimulate the patient’s own anticancer
immune response
Biology: Life on Earth, 9e
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36.9 How Does the Immune System Combat
Cancer?
 Most medical treatments for cancer depend on
selectively killing cancerous cells
– Attempts to eliminate cancer mostly focus on surgery,
radiation, and chemotherapy
– Surgically removing the tumor is the first step in
treating many cancers, but it can be difficult to remove
all the cancerous tissue
– Tumors can be treated with radiation, which can
destroy even microscopic clusters of cancer cells by
disrupting their DNA, thus preventing their cell division
– Neither surgery nor radiation is effective against
cancer that has spread throughout the body
Biology: Life on Earth, 9e
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36.9 How Does the Immune System Combat
Cancer?
 Most medical treatments for cancer depend on
selectively killing cancerous cells (continued)
– Chemotherapy is commonly used to supplement surgery
or radiation
– Chemotherapy drugs attack the machinery of cell
division, so they are somewhat selective for cancer
cells, which divide more frequently than normal cells
do
– Chemotherapy also kills some healthy, dividing cells
– Damage to dividing cells in patient’s hair follicles and
intestinal lining by chemotherapy produces its wellknown side effects of hair loss, nausea, and vomiting
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