Download The Immune System Chapter 43 PowerPoint Lectures for Biology, Seventh Edition

Chapter 43
The Immune System
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: Reconnaissance, Recognition, and
Response
• An animal must defend itself from the many
dangerous pathogens it may encounter
• Two major kinds of defense have evolved: innate
immunity and acquired immunity
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• Innate immunity is present before any exposure to
pathogens and is effective from the time of birth
• It involves nonspecific responses to pathogens
• Innate immunity consists of external barriers plus
internal cellular and chemical defenses
• Key internal defenses are macrophages and other
phagocytic cells
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LE 43-1
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• Acquired immunity, or adaptive immunity,
develops after exposure to agents such as
microbes, toxins, or other foreign substances
• It involves a very specific response to pathogens
• Recognition is by white blood cells called
lymphocytes
• Some lymphocytes produce antibodies; others
destroy infected cells, cancer cells, or foreign
tissue
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LE 43-2
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Skin
Mucous membranes
Secretions
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Phagocytic cells
Antimicrobial proteins
Humoral response
(antibodies)
Inflammatory response
Natural killer cells
Cell-mediated response
(cytotoxic
lymphocytes)
Concept 43.1: Innate immunity provides broad
defenses against infection
• A pathogen that breaks through external defenses
encounters innate cellular and chemical
mechanisms that impede its attack
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External Defenses
• Skin and mucous membranes are physical
barriers to entry of microorganisms and viruses
• Mucous membrane cells produce mucus, a
viscous fluid that traps microbes and other
particles
• In the trachea, ciliated epithelial cells sweep
mucus and any entrapped microbes upward,
preventing microbes from entering the lungs
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• Secretions of the skin and mucous membranes
provide an environment hostile to microbes
• Secretions give the skin a pH between 3 and 5,
acidic enough to prevent colonization of many
microbes
• Skin secretions include proteins such as
lysozyme, which digests bacterial cell walls
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Internal Cellular and Chemical Defenses
• Internal cellular defenses depend mainly on
phagocytosis
• White blood cells called phagocytes ingest
microorganisms and initiate inflammation
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Phagocytic Cells
• Phagocytes attach to prey via surface receptors
and engulf them, forming a vacuole that fuses with
a lysosome
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LE 43-4
Microbes
Pseudopodia
MACROPHAGE
Vacuole
Lysosome
containing
enzymes
• Macrophages, a type of phagocyte, migrate
through the body and are found in organs of the
lymphatic system
• The lymphatic system defends against pathogens
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LE 43-5
Interstitial
fluid
Lymphatic
capillary
Adenoid
Tonsil
Blood
capillary
Lymph
nodes
Spleen
Peyer’s patches
(small intestine)
Tissue
cells
Lymphatic
vessel
Appendix
Lymphatic
vessels
Lymph
node
Masses of
lymphocytes and
macrophages
Antimicrobial Proteins
• Proteins function in innate defense by attacking
microbes directly or impeding their reproduction
• About 30 proteins make up the complement
system, which causes lysis of invading cells and
helps trigger inflammation
• Interferons provide innate defense against viruses
and help activate macrophages
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Inflammatory Response
• In local inflammation, histamine and other
chemicals released from injured cells promote
changes in blood vessels
• These changes allow more fluid, phagocytes, and
antimicrobial proteins to enter tissues
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LE 43-6
Pin
Pathogen
Blood clot
Macrophage
Chemical signals
Phagocytic cells
Capillary
Red blood cell
Blood
clotting
elements
Phagocytosis
Natural Killer Cells
• Natural killer (NK) cells attack virus-infected body
cells and cancer cells
• They trigger apoptosis in the cells they attack
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Invertebrate Immune Mechanisms
• Many invertebrates defend against infection by
many of the same mechanisms in the vertebrate
innate response
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Concept 43.2: In acquired immunity, lymphocytes
provide specific defenses against infection
• Acquired immunity is the body’s second major
kind of defense
• An antigen is a foreign molecule that is recognized
by lymphocytes and elicits a response from them
• A lymphocyte recognizes and binds to a small
portion of the antigen called an epitope
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LE 43-7
Antigenbinding
sites
Antibody A
Antigen
Antibody B
Antibody C
Epitopes
(antigenic
determinants)
Antigen Recognition by Lymphocytes
• Two main types of lymphocytes circulate in the
blood of vertebrates: B lymphocytes (B cells) and
T lymphocytes (T cells)
• A single B cell or T cell has about 100,000
identical antigen receptors
• All antigen receptors on a single cell recognize the
same epitope
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B Cell Receptors for Antigens
• B cell receptors bind to specific, intact antigens
• Secreted antibodies, or immunoglobulins, are
structurally similar to B cell receptors but lack
transmembrane regions that anchor receptors in
the plasma membrane
Video: T Cell Receptors
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LE 43-8
Antigenbinding
site
Light
chain
Antigenbinding
site
Antigenbinding site
Disulfide
bridge
Variable regions
C C
V
Constant regions
V
C C
Transmembrane
region
Heavy chains
B cell
Plasma
membrane
Cytoplasm of B cell
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
b chain
 chain
Disulfide bridge
Cytoplasm of T cell
T cell
A T cell receptor consists of one 
chain and one b chain linked by a
disulfide bridge.
T Cell Receptors for Antigens and the Role of the
MHC
• Each T cell receptor consists of two different
polypeptide chains
V
V
C
C
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• T cells bind to antigen fragments that are bound to
cell-surface proteins called MHC molecules
• MHC molecules are so named because they are
encoded by a family of genes called the major
histocompatibility complex
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• Infected cells produce MHC molecules, which bind
to antigen fragments and are transported to the
cell surface, a process called antigen presentation
• A nearby T cell can then detect the antigen
fragment displayed on the cell’s surface
• Depending on their source, peptide antigens are
handled by different classes of MHC molecules
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• Class I MHC molecules are found on almost all
nucleated cells of the body
• They display peptide antigens to cytotoxic T cells
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LE 43-9
Infected cell
Antigen
fragment
Microbe
Antigenpresenting
cell
Antigen
fragment
Class II MHC
molecule
Class I MHC
molecule
T cell
receptor
T cell
receptor
Cytotoxic T cell
Helper T cell
• Class II MHC molecules are located mainly on
dendritic cells, macrophages, and B cells
• They display antigens to helper T cells
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Lymphocyte Development
• Lymphocytes arise from stem cells in bone
marrow
• Newly formed lymphocytes are alike but later
develop into B cells or T cells, depending on
where they mature
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LE 43-10
Bone marrow
Thymus
Lymphoid
stem cell
B cell
T cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
Generation of Lymphocyte Diversity by Gene
Rearrangement
• Random, permanent gene rearrangement
forms functional genes encoding the B or T cell
antigen receptor chains
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LE 43-11
V4–V39
DNA of
undifferentiated
B cell
V1
V40
V3
V2
J1 J2 J3 J4 J5 Intron
C
Deletion of DNA between a V segment
and J segment and joining of the segments
DNA of differentiated
B cell
V1
V3 J5
V2
Intron
C
Functional gene
Transcription of resulting permanently
rearranged, functional gene
pre-mRNA
V3 J5 Intron
C
RNA processing (removal of intron;
addition of cap and poly (A) tail)
V3 J5
mRNA Cap
C
Poly (A)
Translation
Light-chain polypeptide
V
B cell receptor
C
Variable Constant
region
region
B cell
Testing and Removal of Self-Reactive Lymphocytes
• As B and T cells mature in the bone and thymus,
their antigen receptors are tested for self-reactivity
• Lymphocytes with receptors for antigens that are
already in the body are destroyed by apoptosis or
rendered nonfunctional
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Clonal Selection of Lymphocytes
• In a primary immune response, binding of antigen
to a mature lymphocyte induces the lymphocyte’s
proliferation and differentiation
• This process is called clonal selection
• Clonal selection of B cells generates a clone of
short-lived activated effector cells and a clone of
long-lived memory cells
Animation: Role of B Cells
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LE 43-12
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
• In the secondary immune response, memory cells
facilitate a faster, more efficient response
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LE 43-13
Antibody concentration
(arbitrary units)
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
14
21
28
35
Time (days)
42
49
56
Concept 43.3: Humoral and cell-mediated
immunity defend against different types of threats
• Humoral immune response involves activation and
clonal selection of B cells, resulting in production
of secreted antibodies
• Cell-mediated immune response involves
activation and clonal selection of cytotoxic T cells
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LE 43-14_3
Cell-mediated immune response
Humoral immune response
First exposure to antigen
Intact antigens
Antigens displayed
Antigens engulfed and
by infected cells
displayed by dendritic cells
Activate
Activate
B cells
Gives rise to
Plasma
cells
Memory
B cells
Secreted
cytokines
activate
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Activate
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Helper T Cells: A Response to Nearly All Antigens
• A surface protein called CD4 binds the class II
MHC molecule
• This binding keeps the helper T cell joined to the
antigen-presenting cell while activation occurs
• Activated helper T cells secrete cytokines that
stimulate other lymphocytes
Animation: Helper T Cells
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LE 43-15
Peptide antigen
Dendritic
cell
Class II MHC
molecule
Cytotoxic T cell
Helper T cell
Bacterium
TCR
CD4
Dendritic
cell
Cytokines B cell
Cell-mediated
immunity
(attack on
infected cells)
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytotoxic T Cells: A Response to Infected Cells
and Cancer Cells
• Cytotoxic T cells make CD8, a surface protein
that greatly enhances interaction between a
target cell and a cytotoxic T cell
• Binding to a class I MHC complex on an
infected cell activates a cytotoxic T cell and
makes it an active killer
• The activated cytotoxic T cell secretes proteins
that destroy the infected target cell
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LE 43-16
Released
cytotoxic
T cell
Cytotoxic T cell
Perforin
Cancer
cell
Granzymes
TCR
CD8
Class I MHC
molecule
Target
cell
Pore
Peptide
antigen
Apoptotic
target cell
Cytotoxic
T cell
Animation: Cytotoxic T Cells
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Antibody Classes
• The five major classes of antibodies, or
immunoglobulins, differ in distribution and function
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B Cells: A Response to Extracellular Pathogens
• Activation of B cells is aided by cytokines and
antigen binding to helper T cells
• Clonal selection of B cells generates antibodysecreting plasma cells, the effector cells of
humoral immunity
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LE 43-17
Macrophage
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
CD4
Endoplasmic
reticulum of
plasma cell
+
Cytokines
Helper T cell
Activated
helper T cell
Secreted antibody
molecules
Clone of memory
B cells
LE 43-18a
IgM
(pentamer)
First lg class produced after initial exposure to antigen; then its
concentration in the blood declines
Promotes neutralization and agglutination of antigens; very
effective in complement activation (see Figure 43.19)
J chain
LE 43-18b
IgG
(monomer)
Most abundant lg class in blood; also present in tissue fluids
Only lg class that crosses placenta, thus conferring passive
immunity on fetus
Promotes opsonization, neutralization, and agglutination of
antigens; less effective in complement activation than lgM (see
Figure 43.19)
LE 43-18c
IgA
(dimer)
J chain
Present in secretions such as tears, saliva, mucus, and breast milk
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see Figure 43.19)
Presence in breast milk confers passive immunity on nursing
infant
Secretory
component
LE 43-18d
IgE
(monomer)
Triggers release from mast cells and basophils of histamine and
other chemicals that cause allergic reactions (see Figure 43.20)
LE 43-18e
IgD
(monomer)
Present primarily on surface of naive B cells that have not been
exposed to antigens
Acts as antigen receptor in antigen-stimulated proliferation and
differentiation of B cells (clonal selection)
Transmembrane
region
Antibody-Mediated Disposal of Antigens
• The binding of antibodies to antigens is also the
basis of antigen-disposal mechanisms
• Microbes are eliminated by phagocytosis and
complement-mediated lysis
Animation: Antibodies
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LE 43-19
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host
and opsonization increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Complement
proteins
Bacteria
Virus
Soluble
antigens
Bacterium
Activation of complement system
and pore formation
MAC
Pore
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Active and Passive Immunization
• Active immunity develops naturally in response to
an infection
• It can also develop following immunization, also
called vaccination
• In immunization, a nonpathogenic form of a
microbe or part of a microbe elicits an immune
response to an immunological memory
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• 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
• It can be conferred artificially by injecting
antibodies into a nonimmune person
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Concept 43.4: The immune system’s ability to
distinguish self from nonself limits tissue transplantation
• The immune system can wage war against cells
from other individuals
• Transplanted tissues are usually destroyed by the
recipient’s immune system
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Blood Groups and Transfusions
• Antigens on red blood cells determine whether a
person has type A, B, AB, or O blood
• Antibodies to nonself blood types exist in the body
• Transfusion with incompatible blood leads to
destruction of the transfused cells
• Recipient-donor combinations can be fatal or safe
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• A red blood cell antigen called the Rh factor
creates difficulties when an Rh-negative mother
carries successive Rh-positive fetuses
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Tissue and Organ Transplants
• MHC molecules stimulate rejection of tissue grafts
and organ transplants
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• Chances of successful transplantation increase if
donor and recipient MHC tissue types are well
matched
• Immunosuppressive drugs facilitate
transplantation
• Lymphocytes in bone marrow transplants may
cause a graft versus host reaction in recipients
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Concept 43.5: Exaggerated, self-directed, or
diminished immune responses can cause disease
• If the delicate balance of the immune system is
disrupted, effects range from minor to often fatal
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Allergies
• Allergies are exaggerated (hypersensitive)
responses to antigens called allergens
• In localized allergies such as hay fever, IgE
antibodies produced after first exposure to an
allergen attach to receptors on mast cells
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• The next time the allergen enters the body, it
binds to mast cell–associated IgE molecules
• Mast cells release histamine and other mediators
that cause vascular changes leading to typical
allergy symptoms
• An acute allergic response can lead to
anaphylactic shock, a life-threatening reaction that
can occur within seconds of allergen exposure
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LE 43-20
IgE
Allergen
Granule
Mast cell
Histamine
Autoimmune Diseases
• In individuals with autoimmune diseases, the
immune system loses tolerance for self and turns
against certain molecules of the body
• Rheumatoid arthritis is an autoimmune disease
leading to damage and inflammation of joints
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• Other examples of autoimmune diseases:
– Systemic lupus erythematosus
– Multiple sclerosis
– Insulin-dependent diabetes
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Immunodeficiency Diseases
• Inborn or primary immunodeficiency results from
hereditary or congenital defects that prevent
proper functioning of innate, humoral, and/or cellmediated defenses
• Acquired or secondary immunodeficiency results
from exposure to chemical and biological agents
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Inborn (Primary) Immunodeficiencies
• In severe combined immunodeficiency (SCID),
both the humoral and cell-mediated branches of
acquired immunity fail to function
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Acquired (Secondary) Immunodeficiencies
• Acquired immunodeficiencies range from
temporary states to chronic diseases
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Stress and the Immune System
• Growing evidence shows that physical and
emotional stress can harm immunity
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Acquired Immunodeficiency Syndrome (AIDS)
• People with AIDS are highly susceptible to
opportunistic infections and cancers that take
advantage of an immune system in collapse
• Because AIDS arises from loss of helper T cells, it
impairs both the humoral and cell-mediated
immune responses
• The loss of helper T cells results from infection by
the human immunodeficiency virus (HIV)
Animation: HIV Reproductive Cycle
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• The spread of HIV is a worldwide problem
• The best approach for slowing this spread is
education about practices that transmit the virus
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