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The Immune System
Chapter 43
1
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
2
• 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
3
3 µm
• 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
5
The BIG PICTURE!!!
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
ACQUIRED IMMUNITY
Slower responses to
specific microbes
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
7
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
8
LE 43-3
10 µm
• 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
10
Internal Cellular and Chemical
Defenses
• Internal cellular defenses depend mainly on
phagocytosis
• White blood cells called phagocytes ingest
microorganisms and initiate inflammation
11
Phagocytic Cells
• Phagocytes attach to
prey via surface
receptors and engulf
them, forming a
vacuole that fuses
with a lysosome
12
• Macrophages, a type of phagocyte, migrate
through the body and are found in organs of
the lymphatic system
• The lymphatic system defends against
pathogens
13
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
15
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
Pin
Pathogen
Blood clot
Macrophage
Chemical signals
Phagocytic cells
Capillary
Red blood cell
Blood
clotting
elements
Phagocytosis
16
Natural Killer Cells
• Natural killer (NK)
cells attack virusinfected body cells
and cancer cells
• They trigger
apoptosis in the cells
they attack
17
Invertebrate Immune
Mechanisms
• Many invertebrates defend against infection by
many of the same mechanisms in the vertebrate
innate response
18
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
19
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
SPECIFICITY IS THE WORD!!!
21
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
22
Antigenbinding
site
Antigenbinding
site
Antigenbinding site
Disulfide
bridge
Light
chain
Variable regions
C C
Constant regions
V
V
C
C
Transmembrane
region
Heavy chains
Plasma
membrane
 chain
b chain
Disulfide bridge
B cell
Cytoplasm of B cell
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
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
24
• 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
25
• 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
26
• Class I MHC
molecules are found on
almost all nucleated
cells of the body
• They display peptide
antigens to cytotoxic
T cells
27
• Class II MHC
molecules are located
mainly on dendritic
cells, macrophages,
and B cells
• They display antigens
to helper T cells
Dendritic cells have lots of
“arms” – they act as antigenpresenting cells
28
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
29
Bone marrow
B
Thymus
Lymphoid
stem cell
B cell
T cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T
Generation of Lymphocyte
Diversity by Gene Rearrangement
• Random, permanent gene rearrangement forms
functional genes encoding the B or T cell
antigen receptor chains
31
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
Let’s not go
pre-mRNA
here…
Transcription of resulting permanently
rearranged, functional gene
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 SelfReactive 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
33
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
34
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
Antibody concentration
(arbitrary units)
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
14
21
28
35
42
49
56
Time (days)
36
Why kids need shots…
37
and teens too!
CDC has all the info about immunizations
38
Concept 43.3: Humoral and cellmediated immunity defend
against different types of
threats
• Humoral immune response involves activation
and clonal selection of B cells, resulting in
production of specific secreted antibodies
• Cell-mediated immune response involves
activation and clonal selection of cytotoxic T
cells
39
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
Another
BIG
PICTURE
to put it
all
together
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
41
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
43
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
Antibody Classes
•The five major classes of antibodies, or immunoglobulins,
differ in distribution and function
•They are called IgA, IgD, IgE,IgG and IgM
45
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
46
LE 43-17
Macrophage
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
CD4
Secreted antibody
molecules
Endoplasmic
reticulum of
plasma cell
+
Cytokines
Helper T cell
Activated
helper T cell
Clone of memory
B cells
Why is there lots of ER in this cell?
The Immunoglobulin Family
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
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)
Opsonization = marking antigen for destruction/phagocytosis
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
IgE
(monomer)
IgD
(monomer)
Triggers release from mast cells and basophils of histamine and
other chemicals that cause allergic reactions (see Figure 43.20)
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
50
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 and an
immunological memory
52
•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
53
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
54
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
55
You already know this from genetics
56
•A red blood cell antigen called the Rh factor
creates difficulties when an Rh-negative mother
carries successive Rh-positive fetuses
Check it out on the web
57
Tissue and Organ Transplants
•MHC molecules stimulate
rejection of tissue grafts
and organ transplants
•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
58
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
59
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
•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
60
that can occur within seconds of allergen exposure
LE 43-20
Why
don’t bees get hay fever? Aren’t pollen grains neat?
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
62
•Other examples of
autoimmune diseases:
– Systemic lupus
erythematosus
– Multiple sclerosis
– Insulin-dependent
diabetes
63
Immunodeficiency Diseases
• Inborn or primary immunodeficiency results
from hereditary or congenital defects that
prevent proper functioning of innate, humoral,
and/or cell-mediated defenses
• Acquired or secondary immunodeficiency
results from exposure to chemical and
biological agents
64
Inborn (Primary)
Immunodeficiencies
•In severe combined immunodeficiency (SCID), both the
humoral and cell-mediated branches of acquired immunity
fail to function
65
Acquired (Secondary)
Immunodeficiencies
•Acquired
immunodeficiencies
range from temporary
states to chronic
diseases
66
Stress and the Immune System
•Growing evidence shows that physical and
emotional stress can harm immunity
67
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 cellmediated immune responses
• The loss of helper T cells results from infection
by the human immunodeficiency virus (HIV)
Animation: HIV Reproductive Cycle
68
HIV
1 µm
•The spread of HIV is a worldwide problem
•The best approach for slowing this spread is education
about practices that transmit the virus
70