Chapter 47
Animal Defenses
Against Infection
Lecture Presentations by
NicoleTunbridgeand
© 2021 Pearson Education Ltd. Kathleen Fitzpatrick
Figure 47.1b
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© 2021 Pearson Education Ltd.
CONCEPT 47.1: In innate immunity, recognition
and response rely on traits common to groups
of pathogens
• Pathogens are agents that cause disease, such as
bacteria, viruses, fungi, or others
• Dedicated cells of the immune system enable
animals to avoid or limit many infections
• First lines of defense help prevent pathogens from
gaining entry to the body
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• Within the body, two types of molecular recognition
allow detection of nonself molecules, particles, and
cells
• All animals have innate immunity, a defense active
immediately upon infection
• Innate immunity includes barrier defenses
• Vertebrates also have adaptive immunity
• The adaptive immune response is activated after
the innate response and develops more slowly
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Innate Immunity of Invertebrates
• In insects, an exoskeleton made of chitin forms the
first barrier to pathogens
• The digestive system is protected by a chitin-based
barrier and lysozyme, an enzyme that breaks down
bacterial cell walls
• Insect immune cells produce recognition proteins,
each of which binds a molecule common to a large
class of pathogens
• The major immune cells of insects are called
hemocytes
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Figure 47.2
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© 2021 Pearson Education Ltd.
• Some hemocytes ingest and break down
microorganisms through phagocytosis
• Hemocytes also secrete antimicrobial peptides that
inactivate or kill fungi or bacteria
• Binding of recognition proteins to fungal cell wall
molecules activates a transmembrane receptor
called Toll
• Toll then activates production and secretion of
antimicrobial peptides that kill fungal cells
• Insects also have defenses against viruses
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• Many viruses that infect insects have a genome
consisting of a single strand of RNA
• This is converted into double-stranded RNA inside
the host cell
• As double-stranded RNA is not produced by
animals, it can trigger a specific defense against the
invading virus
Figure 47.3
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© 2021 Pearson Education Ltd.
Innate Immunity of Vertebrates
• Some innate defenses of mammals are similar to
those of invertebrates
• These include barrier defenses, phagocytosis,
and antimicrobial peptides
• Additional defenses unique to vertebrates are
natural killer cells, interferons, and the
inflammatory response
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Barrier Defenses
• Barrier defenses include the skin and mucous
membranes of the respiratory, urinary, and
reproductive tracts
• Mucus traps and allows for the removal of
microbes
• Many body fluids including saliva, mucus, and
tears are hostile to many microbes
• The low pH of skin and the digestive system
prevents growth of many bacteria
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Cellular Innate Defenses
• Innate immune cells in mammals detect, devour,
and destroy invading pathogens
• These cells recognize groups of pathogens using
TLRs, or Toll-like receptors
• TLRs recognize fragments of molecules
characteristic of a set of pathogens
Figure 47.4
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© 2021 Pearson Education Ltd.
• There are two main types of phagocytic cells,
which engulf and destroy pathogens, in the
mammalian body:
– Neutrophils circulate in the blood
– Macrophages migrate through the body or reside
permanently in organs and tissues
• There are two additional types of phagocytic cells:
– Dendritic cells stimulate development of
adaptive immunity
– Eosinophils discharge destructive enzymes
against parasites
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• Cellular innate defenses in vertebrates also
involve natural killer cells
• These circulate through the body and detect
abnormal cells
• They release chemicals leading to cell death,
inhibiting the spread of virally infected or
cancerous cells
• Many cellular innate defenses involve the
lymphatic system
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Local Inflammatory Response
• The inflammatory response, including heat and
swelling, is brought about by molecules released
upon injury or infection
• Mast cells, immune cells found in connective tissue,
discharge cytokines, signaling molecules that recruit
neutrophils to the site
• They also release histamine, which triggers blood
vessels to dilate and become more permeable
• The resulting increase in blood supply produces the
inflammatory response
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Figure 47.5
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© 2021 Pearson Education Ltd.
• Cycles of signaling and response, continue the
process of inflammation
• Enhanced blood flow to the site, helps deliver
antimicrobial peptides
• The result is an accumulation of pus, a fluid rich in
white blood cells, dead pathogens and debris from
damaged tissue
• At the end of the local inflammatory response, pus
and excess fluid are taken up as lymph
• This fluid is transported in the body by the lymphatic
system
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• Lymph nodes, throughout the body, contain
macrophages, which engulf pathogens that enter
the lymph
• Dendritic cells migrate to lymph nodes after
interacting with pathogens, and stimulate adaptive
immunity
Figure 47.6
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© 2021 Pearson Education Ltd.
Systemic and Chronic Inflammation
• More extensive tissue damage or infection can lead
to a response that is systemic (throughout the body)
• Cells in the injured or infected tissue often secrete
molecules that stimulate the release of additional
neutrophils from bone marrow
• In the case of severe infection, the number of white
blood cells in the bloodstream may increase
severalfold within a few hours
• A systemic inflammatory response sometimes
involves fever
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• Substances released by macrophages activated by
certain pathogens, cause the body’s thermostat to
reset to a higher temperature
• It is possible that this may enhance phagocytosis
and accelerate tissue repair.
• Certain bacterial infections can induce an
overwhelming system inflammatory response
• This leads to a life-threatening condition called
septic shock.
• It is fatal in more than one third of cases, and
occurs more often in the very old and very young •
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Crohn’s disease and ulcerative colitis are
debilitating disorders in which chronic (ongoing)
inflammation disrupts intestinal function
Antimicrobial Peptides and Proteins
• Pathogen recognition in mammals, triggers the
production and release of peptides that attack
pathogens or impede their reproduction
• Interferons are proteins that provide innate defense
by inhibiting the replication of viruses
• Some types of interferons help activate
macrophages
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• The complement system consists of about 30
proteins in blood plasma
• These are activated by substances on the surface
of many pathogens
• A resulting cascade of reactions lead to lysis
(bursting) of the invading cells
• The complement system also functions in the
inflammatory response and in adaptive defense
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Evasion of Innate Immunity by Pathogens
• Some pathogens avoid destruction because their
outer capsule interferes with molecular recognition
and phagocytosis
• Streptococcus pneumoniae is one such bacterium,
a major cause of pneumonia and meningitis in
humans
• Mycobacterium tuberculosis, can be recognized by
the host but resists breakdown
• This organism causes tuberculosis (TB), a disease
that kills more than 1 million people per year
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CONCEPT 47.2: In adaptive immunity, receptors
provide pathogen-specific recognition
• Unlike innate immunity, the adaptive response is
enhanced by previous exposure to the pathogen
• The adaptive response relies on two types of
lymphocytes, or white blood cells
• Lymphocytes that mature in the thymus, above the
heart, are called T cells, and those that mature in
bone marrow are called B cells
Figure 47.8
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© 2021 Pearson Education Ltd.
Antigens as the Trigger for Adaptive Immunity
• Antigens are substances that can elicit a response
from a B or T cell
• T or B cells bind to antigens via antigen receptors
specific to part of one molecule of that pathogen
• The cells of the immune system produce millions of
different antigen receptors
• Antigens are usually foreign, and typically large
molecules, either proteins or polysaccharides
• Other antigens are toxins secreted by bacteria
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• The small, accessible part of an antigen that binds
to an antigen receptor is called an epitope
• Each individual B or T cell is specialized to
recognize a specific type of molecule
• The antigen receptors of B cells and T cells have
similar components, but they encounter antigens in
different ways
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Antigen Recognition by B Cells and Antibodies
• Each B cell antigen receptor is a Y-shaped molecule
with two identical heavy chains and two identical
light chains
• The constant (C) regions of these chains vary little
among B cells, whereas the variable (V) regions
differ greatly
• The variable regions provide antigen specificity
Figure 47.9
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© 2021 Pearson Education Ltd.
• Binding of a B cell antigen receptor to an antigen is
an early step in B cell activation
• This gives rise to cells that secrete a soluble form of
the receptor called an antibody or
immunoglobulin (Ig)
• Antibodies have the same Y shape as B cell antigen
receptors but are secreted, not membrane bound
Figure 47.10
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© 2021 Pearson Education Ltd.
Antigen Recognition by T Cells
• Each T cell receptor consists of two different
polypeptide chains (called α and β)
• The tips of the chain form a variable (V) region
• Here, the α and β chains together form a single
antigen-binding site
• The rest is a constant (C) region
Figure 47.11
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© 2021 Pearson Education Ltd.
• T cells bind only to antigen fragments displayed or
presented on a host cell
• These antigen fragments are bound to cell-surface
proteins called major histocompatibility complex
(MHC) molecules
• MHC molecules are host proteins that display the
antigen fragments on the cell surface
Figure 47.12
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© 2021 Pearson Education Ltd.
• In infected cells, MHC molecules bind and transport
antigen fragments to the cell surface, a process
called antigen presentation
• A T cell can then bind both the antigen fragment and
the MHC molecule
• This interaction is necessary for the T cell to
participate in the adaptive immune response
Figure 47.13
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B Cell and T Cell Development
• The adaptive immune system has four major
characteristics:
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– Immense diversity of lymphocytes and receptors
– Self-tolerance: lack of reactivity against an animal’s
own molecules and cells
– B and T cells proliferate after activation
– Immunological memory
The Basis of B Cell and T Cell Diversity
• By combining variable elements, the immune
system assembles millions of different antigen
receptors from a small number of parts
• An immunoglobulin (Ig) gene encodes the light
chain of the B cell receptor
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• Many different chains can be produced from the
same gene by rearrangement of the V, J, and C
regions
• The capacity to generate diversity is built into the
structure of Ig genes
• The light chain is encoded by three segments:
– A variable (V) segment
– A joining (J) segment
– A constant (C) segment
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• The V and J segments together encode the variable
region of the receptor while the C segment encodes
the constant region
• The light chain gene contains a single C segment
• It has 40 different V segments and 5 different J
segments
• The pieces can be combined in 200 different ways
• The number of heavy chain combinations is greater,
resulting in more diversity
Antigen Receptor Gene Rearrangement
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• Assembling a functional Ig gene requires
rearrangement of the DNA
• And enzyme complex called recombinase acts
randomly to connect different V and J segments in
each B cell
• Light and heavy chain genes both undergo these
rearrangements
• In any given cell there is only one allele of a
lightchain gene and only one allele of a heavy-chain
gene
Figure 47.14
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© 2021 Pearson Education Ltd.
• The Ig gene rearrangements are permanent and
passed on to daughter cells when the lymphocyte
divides
• The rearranged genes are transcribed and
translated to produce unique antigen receptors
• There are millions of different arrangements
possible among humans
• Mutations introduced during VJ recombination
contribute even more diversity
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Origin of Self-Tolerance
• Antigen receptors are generated by random
rearrangement of DNA
• As lymphocytes mature in bone marrow or the
thymus, they are tested for self-reactivity
• Some B and T cells with receptors specific for the
body’s own molecules are destroyed by apoptosis,
or programmed cell death
• The remainder are rendered nonfunctional, leaving
only lymphocytes that react to foreign molecules
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Proliferation of B Cells and T Cells
• In the body there are few lymphocytes with antigen
receptors specific for any particular epitope
• In the lymph nodes, an antigen is exposed to a
steady stream of lymphocytes until a match is made
• This binding of a mature lymphocyte to an antigen
initiates events that activate the lymphocyte bearing
the receptor
• Once activated, a B or T cell undergoes multiple cell
divisions (clonal selection) to produce a clone of
identical cells
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• Some cells from the clone become effector cells
that act immediately against the antigen
• Effector cells are plasma cells that secrete
antibodies
• The remaining cells in the clone become long-lived
memory cells that can give rise to effector cells if
the same antigen is encountered again
Figure 47.15
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© 2021 Pearson Education Ltd.
Figure 47.16
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© 2021 Pearson Education Ltd.
Immunological Memory
• Immunological memory is responsible for long-term
protections against diseases
• The first exposure to a specific antigen represents
the primary immune response
• A clone of lymphocytes is formed that are specific to
the pathogen
• In the secondary immune response, memory cells
facilitate a faster, greater, and more prolonged
response from a reservoir of T and B memory cells
Figure 47.17
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© 2021 Pearson Education Ltd.
CONCEPT 47.3: Adaptive immunity defends
against infection of body fluids and body cells
• The defenses provided by B and T lymphocytes can
be divided into the humoral immune response and
the cell-mediated immune response
• In the humoral immune response, antibodies help
neutralize or eliminate toxins and pathogens in the
blood and lymph
• In the cell-mediated immune response,
specialized T cells destroy infected host cells
Helper T Cells: Activating Adaptive Immunity
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• A type of T cell called a helper T cell activates both
the humoral and cell-mediated immune responses
• This requires the presence of a foreign molecule
that can bind the antigen receptor on the helper T
cell
• And, the antigen must be displayed on the surface
of an antigen-presenting cell
• Antigen-presenting cells have class I and II MHC
molecules on their surfaces
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• Class Ⅱ MHC molecules provide a molecular
signature by which antigen-presenting cells are
recognized
• Antigen receptors on the surface of helper T cells
bind to the antigen and the class Ⅱ MHC molecule;
then cytokine signals are exchanged between the
two cells
• The helper T cell is stimulated to produce its own
set of cytokines
Figure 47.18
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© 2021 Pearson Education Ltd.
B Cells and Antibodies: A Response to
Extracellular Pathogens
• The humoral response is characterized by
secretion of antibodies by clonally selected B cells
• It begins with activation of the B cells
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Activation of B Cells
• Activation of B cells involves helper T cells and
proteins on the surface of pathogens
• When an antigen binds a B cell, the cell takes in a
few foreign molecules by receptor-mediated
endocytosis
• The class Ⅱ MHC protein of the B cell then presents
an antigen fragment to a helper T cell, a process that
is critical to B cell activation
Figure 47.19
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© 2021 Pearson Education Ltd.
•
An activated B cell gives rise to thousands of
identical plasma cells
• These begin producing and secreting antibodies
• Most antigens recognized by B cells contain
multiple epitopes
• A variety of B cells activated by one antigen will
give rise to plasma cells producing antibodies
directed against different epitopes of the common
antigen
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Antibody Function
• Antibodies do not kill pathogens; instead, they mark
pathogens for inactivation or destruction
• In neutralization, antibodies bind to viral surface
proteins, preventing infection of a host cell
• Antibodies may also bind to toxins in body fluids
and prevent them from entering body cells
In opsonization, antibodies bind to antigens on
bacteria, promoting phagocytosis
• When antibodies facilitate phagocytosis, they also
help fine-tune the humoral immune response
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•
• Positive feedback between the innate and adaptive
immunity contributes to a coordinated, effective
response to infection
Figure 47.20
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© 2021 Pearson Education Ltd.
•
Antibodies may work with the proteins of the
complement system
• Binding of a complement protein to an
antigenantibody complex on a foreign cell leads to
formation of a pore in the membrane of the cell
• Water and ions rush into the cell, causing swelling
and lysis
Figure 47.21
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© 2021 Pearson Education Ltd.
• B cells can express five different forms (or classes)
of immunoglobulin (Ig) with similar antigen-binding
specificity but different heavy chain C regions
• IgD is membrane bound, while the other four, IgA,
IgE, IgG, and IgM, are soluble
Cytotoxic T Cells: A Response to Infected Host
Cells
• Cytotoxic T cells use toxic proteins to kill cells
infected by viruses or other intracellular pathogens
• Cytotoxic T cells recognize fragments of foreign
proteins produced by infected cells
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• The activated cytotoxic T cell secretes proteins that
disrupt the membranes of target cells and trigger
apoptosis
Figure 47.22
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© 2021 Pearson Education Ltd.
Summary of the Humoral and Cell-Mediated
Immune Responses
• Both the humoral and cell-mediated responses can
include primary and secondary immune responses
• Memory cells of each type enable the secondary
response
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Figure 47.23
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© 2021 Pearson Education Ltd.
Immunization
• The protection provided by a second immune
response provides the basis for immunization
• Antigens are artificially introduced into the body to
generate adaptive immune response and memory
cell formation
• Vaccines used today for immunization are made
with inactivated bacterial toxins, killed or weakened
pathogens, or even genes encoding microbial
proteins
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• Vaccination programs have been successful against
many infectious diseases
• Not all pathogens are easily managed by
vaccination and some vaccines are not readily
available in impoverished areas
• Misinformation about vaccine safety has led to a
growing public health problem
Figure 47.24
小兒麻痺
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麻疹
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Active and Passive Immunity
• Active immunity develops naturally when a
pathogen invades the body and elicits a primary or
secondary immune response
• Passive immunity provides immediate, short-term
protection
• It is conferred naturally when IgG crosses the
placenta from mother to fetus or when IgA passes
from mother to infant in breast milk
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• In artificial passive immunization, antibodies from an
immune animal are injected into a nonimmune
animal
• For example humans bitten by venomous snakes
are sometimes treated with antivenin
• This is serum from sheep or horses immunized
against snake venom
• Antibodies in antivenin can neutralize toxins in the
snake venom
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Antibodies as Tools
• Antibodies produced by an animal after exposure to
an antigen are the products of many different clones
of plasma cells
• However, monoclonal antibodies can be prepared
from a single clone of B cells grown in culture
• These antibodies are identical and specific for the
same epitope
• Monoclonal antibodies are used in many types of
medical diagnoses and treatments
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• Home pregnancy kits use monoclonal antibodies to
detect human chorionic gonadotropin (hCG)
• This hormone is a reliable indicator of early
pregnancy
• Monoclonal antibodies are used as therapies for
some cancers
• They can also be used to identify every virus a
person has encountered, either through infection or
immunization
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© 2021 Pearson Education Ltd.
Immune Rejection
• Cells transferred from one person to another can be
attacked by immune defenses
• This complicates the transplantation of tissues or
organs
• To minimize rejection of a transplant or graft,
surgeons use donor tissue with MHC molecules as
similar as possible to those of the recipient
• In addition, the recipient takes medicines that
suppress immune responses
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Blood Groups
• Antigens on red blood cells determine whether a
person has blood type A (A antigen), B (B antigen),
AB (both A and B antigens), or O (neither antigen)
• Antibodies to nonself blood types exist in the body
• Transfusion with incompatible blood can lead to
lysis of the introduced cells, and chills, fever, shock,
and perhaps kidney malfunction
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Exaggerated, Self-Directed, and Diminished
Immune Responses
• When allergic, autoimmune, or immunodeficiency
disorders disrupt the delicate balance of immune
responses, the effects can be severe
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Allergies
• Allergies are exaggerated (hypersensitive)
responses to antigens called allergens
• Hay fever occurs when plasma cells secrete IgE
antibodies specific for antigens on the surface of
pollen grains
• The next time pollen grains enter the body, they
bind the IgE antibodies and induce mast cells to
release histamine and other inflammatory chemicals
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• Typical allergy symptoms include: sneezing, runny
nose, teary eyes, and smooth muscle contractions
in the lungs
• An acute allergic response can lead to anaphylactic
shock, a life-threatening reaction, within seconds of
allergen exposure
• An injection of epinephrine can rapidly counteract
the allergic response
Figure 47.26
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© 2021 Pearson Education Ltd.
Autoimmune Diseases
• In individuals with autoimmune diseases, the
immune system loses tolerance for self and turns
against certain molecules of the body
• In systemic lupus, the immune system generates
antibodies against histones and DNA released by
normal breakdown of body cells
• These self-reactive antibodies cause rashes, fever,
arthritis, and kidney dysfunction
• Type 1 diabetes is another autoimmune condition
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• Heredity, gender, and environment all influence
susceptibility to autoimmune disorders
• Many such diseases affect females more often than
males
• Rheumatoid arthritis is a damaging and painful
inflammation of the cartilage and bone in joints
Figure 47.27
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© 2021 Pearson Education Ltd.
Immunodeficiency Diseases
• Inborn immunodeficiency results from a genetic or
developmental defect in the innate or adaptive
defenses, or both
• Acquired immunodeficiency develops later in life
due to exposure to chemical and biological agents
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Attack on the Immune System: HIV
• Human immunodeficiency virus (HIV) infects
helper T cells
• HIV persists in the host—despite an immune
response—because it has a high mutation rate that
promotes antigen variation
• Over time, an untreated HIV infection not only
avoids the adaptive immune response, but also
abolishes it
Figure 47.28
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© 2021 Pearson Education Ltd.
• HIV infection leads to acquired immunodeficiency
syndrome (AIDS)
• People with AIDS are highly susceptible to
opportunistic infections and cancers that a normal
immune system would usually defeat
• The spread of HIV is a worldwide problem
• The best approach for slowing this spread is
education about practices that transmit the virus
Cancer and Immunity
• The frequency of certain cancers increases when
adaptive immunity is inactivated
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• 15–20% of all human cancers involve viruses
• The immune system can act as a defense against
viruses that cause cancer and cancer cells that
harbor viruses
• Scientists have identified six viruses that can cause
cancer in humans
• Kaposi’s sarcoma herpes virus is associated with
cancer
• Hepatitis B virus, can trigger liver cancer; a vaccine
for this virus was introduced in 1986
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• Human papilloma virus (HPV) is associated with
cervical and some oral cancers
• In 2006, a vaccine to protect against HPV was first
released
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