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College
CHAPTER
17
Adaptive
Immunity:
Specific
Defenses of
the Host
© 2016 Pearson Education, Ltd.
The Adaptive Immune System
 Innate immunity: Defenses against any pathogen.
 Adaptive immunity: Specific antibody and lymphocyte
response to an antigen.
 Acquired through infection or vaccination
 Primary response: first time the immune system combats
a particular foreign substance
 Secondary response: later interactions with the same
foreign substance; faster and more effective due to
"memory"
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Dual Nature of the Adaptive Immune System
 1887, Louis Pasteur observed immunity in chickens
injected with weakened pathogens.
 Emil Von Behring, working with diphtheria and tetanus
bacteria, received the first Nobel Prize (in 1901) for
development of antitoxin.
 Paul Ehrlich’s, received Nobel Prize in 1908, work led
to the identification of antibodies in serum.
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Terminology
 Antigen (Ag): A substance that causes the body to
produce specific antibodies or sensitized T cells.
 Antibody (Ab): Proteins made in response to an Ag;
can combine with that Ag.
 Complement: Serum proteins that bind to Ab in an AgAb reaction; cause cell lysis.
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Overview of Humoral Immunity 漿液免疫反應
 Humoral immunity involves antibodies produced by B
cells.
 Bursa of Fabricius 法氏囊
 B cells recognize antigens by antibodies on their
surfaces.
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Overview of Cellular Immunity
 Cell-mediated immunity involved T cells.
 Recognize antigenic peptides processed by phagocytic
cells
 Mature in the thymus
 T cell receptors (TCRs) on the T cell surface contact
antigens, causing the T cells to secrete cytokines
instead of antibodies.
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Figure 17.1 Differentiation of T cells and B cells.
Stem cells develop
in bone marrow or
in fetal liver
Stem cell
(diverges into
two cell lines)
Red bone
marrow
of adults
Thymus
Differentiate to
B cells in adult
red bone marrow
Differentiate to
T cells in thymus
T cell
B cell
Migrate to lymphoid
tissue such as spleen,
but especially lymph
nodes
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 Cellular immunity attacks antigens found inside cells
 Viruses; some fungi and parasites
 Humoral immunity fights invaders outside cells
 Bacteria and toxins
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Cytokines: Chemical Messengers of Immune
Cells
 Cytokines are chemical messengers produced in
response to a stimulus.
 Interleukins: cytokines between leukocytes
 Chemokines: induce migration of leukocytes
 Interferons (IFNs): interfere with viral infections of host
cells
 Tumor necrosis factor (TNF): involved in the
inflammation of autoimmune diseases
 Hematopoietic cytokines: control stem cells that
develop into red and white blood cells
 Overproduction of cytokines leads to a cytokine storm.
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第9版 Table 17.3
Antigens and Antibody
The Nature of Antigens
 Antigens (Antibody generators)
 Most antigens are either proteins or large polysaccharides.
 Lipids and nucleic acids are usually antigenic only
when combined with proteins and polysaccharides.
 Antibodies recognize and react with antigenic
determinants or epitopes on an antigen.
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Figure 17.2 Epitopes (antigenic determinants).
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 Antigenic compounds are
 Microbial components: Capsules, cell wall, flagella,
fimbriae, toxins of bacteria, coats of viruses, other types
of microbial surfaces
 Non-microbial: pollens, egg white, blood cell surface
molecules, serum proteins from others, surface
molecules of transplanted tissue or organs
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 Haptens are molecules too small to stimulate antibody
formation by themselves unless they are attached to a
carrier molecules. Carrier proteins are usually serum
proteins.
 Ex: penicillin
Figure 17.3 Haptens.
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Antibodies
Antibody Structure
 An antibody has at least two identical antigen-binding (valence)
sites
 A single bivalent antibody unit is a monomer.
 Typical monomers consist of four polypeptide chains.
 Within each chain is a variable (V) region, where antigen
binding occurs, and a constant (C) region, which serves as a
basis for distinguishing the classes of antibodies.
 An antibody monomer is Y- or T-shaped; the variable regions
form the tips, and the constant regions form the base and Fc
(stem) region.
 The Fc region can attach to a host cell or complement.
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Figure 17.4 The structure of a typical antibody molecule.
Antigenbinding
site
Antigen
Epitope
(antigenic
determinant)
Fc (stem) region
C
Antibody molecule
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C
Hinge region
Antibodies
Antigen-binding
site
Enlarged antigen-binding site
bound to an epitope
Antibody molecules
shown by atomic force microscopy
Immunoglobulin classes
IgG antibodies
 Monomer
 80% of serum antibodies
 Fix complement
 In blood, lymph, and intestine
 Cross placenta
 Enhance phagocytosis; neutralize
toxins and viruses; protects fetus and
newborn
 Half-life = 23 days
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Table 17.1 (1 of 3)
IgM Antibodies
 Pentamer
 5-10% of serum antibodies
 Fix complement
 In blood, lymph, and on B
cells
 Agglutinates microbes; first
Ab produced in response to
infection
 Half-life = 5 days
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Table 17.1 (2 of 3)
IgA Antibodies
 Dimer
 10-15% of serum antibodies
 In secretions
 Mucosal protection
 Half-life = 6 days
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Table 17.1 (3 of 3)
IgD Antibodies
 Monomer
 0.2% of serum antibodies
 In blood, lymph, and on B cells
 On B cells, initiate immune
response
 Half-life = 3 days
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Table 17.1 (1 of 3)
IgE Antibodies
 Monomer
 0.002% of serum antibodies
 On mast cells, basophils, and in
blood
 Allergic reactions; lysis of parasitic
worms
 Half-life = 2 days
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Table 17.1 (1 of 3)
Table 17.1 A Summary of Immunoglobulin Classes
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Humoral Immunity Response Process
Clonal Selection of Antibody-Producing Cells
 Major histocompatibility complex (MHC) genes
encode molecules on the cell surface.
 Class I MHC are on the membrane of nucleated animal
cells
 Identify "self"
 Class II MHC are on the surface of antigen-presenting
cells (APCs), including B cells
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 Inactive B cells contain surface Ig that bind to antigen
 B cell internalizes and processes antigen
 Antigen fragments are displayed on MHC class II
molecules
 T helper cell (TH) contacts the displayed antigen
fragment and releases cytokines that activate B cells
 B cell undergoes proliferation (clonal expansion)
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Figure 17.5 Activation of B cells to produce antibodies.
Major histocompatibility complex 主要組織相容性複合體
Extracellular
antigens
B cell
receptors
Antigen
fragments
MHC class II with
antigen displayed
on surface
Cytokines
Plasma cell
Antibodies
TH cell
B cell
B cell
B cell receptors
recognize and
attach to antigen.
Antigen is
internalized into
the B cell.
Fragments of the
antigen are presented
on MHC proteins on
the surface of the cell.
(APC)
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A T helper cell that recognizes
this antigen fragment is
activated and releases
cytokines, activating the B cell.
The activated B cell begins
clonal expansion, producing an
army of antibody-producing
plasma cells and memory cells.
 Clonal selection differentiates activated B cells into:
 Antibody-producing plasma cells
 Memory cells
 Clonal deletion eliminates harmful B cells
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Figure 17.6 Clonal selection and differentiation of B cells.
Stem cell
Stem cells differentiate into mature B cells,
each bearing surface immunoglobulins
against a specific antigen.
Immunoglobin
B cell
I
II
Antigens
B cell II encounters its specific antigen
and proliferates.
Some B cells proliferate into long-lived
memory cells, which at a later date can be
stimulated to become antibodyproducing plasma cells.
Memory
cell
Plasma
cell
Plasma cells secrete antibodies
into circulation.
Blood vessel of cardiovascular system
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Other B cells proliferate
into antibody-producing
plasma cells.
 An antigen that requires a TH cell for antibody production
is known as a T-dependent antigen.
 Ex: viruses, bacteria, foreign RBC, haptens with their carrier
molecules.
 Antigens that stimulate B cells directly without the help of
T cells are called T-independent antigen.
 Ex: repeating subunits such as polysaccharides,
lipopolysaccharides
 Stimulate the B cell without the help of T cells
 Provoke a weak immune response, usually producing IgM
 No memory cells generated
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Figure 17.7 T-independent antigens.
Polysaccharide
(T-independent antigen)
Epitopes
B cell receptors
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Antigen-Antibody Binding and Its Results
 Affinity (親和性): the strength of the bond between an
Ag and an Ab.
 Specificity (專一性): Ab recognizes a specific epitope.
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 An antigen–antibody complex forms when
antibodies bind to antigens
 Strength of the bond is the affinity
 Protects the host by tagging foreign molecules or cells
for destruction
 Agglutination
 Opsonization
 Antibody-dependent cell-mediated cytotoxicity
 Neutralization
 Activation of the complement system
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Figure 17.8 The results of antigen–antibody binding.
PROTECTIVE MECHANISM
OF BINDING ANTIBODIES
TO ANTIGENS
Agglutination
Activation of complement
Causes inflammation and cell lysis
Reduces number of infectious
units to be dealt with
Complement
Antibody
Bacteria
Lysis
Bacterium
Antibody-dependent cell-mediated cytotoxicity
Opsonization
Coating antigen with antibody
enhances phagocytosis
Antibodies attached to target cell
cause destruction by macrophages,
eosinophils, and NK cells
Eosinophil
Epitopes
Phagocyte
Perforin
and lytic
enzymes
Large target cell (parasite)
Neutralization
Blocks adhesion of bacteria
and viruses to mucosa
Blocks attachment
of toxin
Virus
Toxin
Bacterium
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Cellular Immunity Response Process
 T cells combat intracellular pathogens
 Mature in the thymus
 Thymic selection eliminates immature T cells
 Migrate from the thymus to lymphoid tissues
 Attach to antigens via T-cell receptors (TCRs)
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 Pathogens entering the gastrointestinal tract pass
through microfold cells (M cells) located over
Peyer's patches
 Transfer antigens to lymphocytes and antigenpresenting cells (APCs)
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 M (microfold)
cells and Peyer’s
patches
Figure 16.5 The lymphatic system.
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Figure 17.9 M cells.
M cell on Peyer's patch. Note the tips of the closely
packed microvilli on the surrounding epithelial cells.
Antigen
M cell
Microvilli on
epithelial cell
TH cell
Pocket
B cells
Macrophage
Epithelial cell
M cells facilitate contact between antigens passing through the intestinal
tract and cells of the body's immune system.
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Antigen-Presenting Cells (APCs)
 Dendritic cells (DCs)
 Engulf and degrade microbes and display them to
T cells
 Found in the skin, genital tract, lymph nodes, spleen, thymus,
and blood
 Macrophages
 Activated by cytokines or the ingestion of antigenic material
 Migrate to the lymph tissue, presenting antigen to T cells
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Figure 17.10 A dendritic cell.
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Figure 17.11 Activated macrophages.
Activated
macrophages
Resting (inactive)
macrophage
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Classes of T Cells
 T-Cells are classified according to their functions and cell
surface receptors called CD (Clusters of Differentiation)
 CD4
 T helper cells (TH)
 Cytokine signaling with B cells; interact directly with antigens
 Bind MHC class II molecules on B cells and APCs
 CD8
 Cytoxic T lymphocytes (CTL)
 Bind MHC class I molecules
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T Helper Cells (CD4+ T Cells):
 TCR on the TH cell recognize and bind to the antigen
fragment and MHC class II on APC
 APC or TH secrete a costimulatory molecule,
activating the TH cell
 TH cells produce cytokines and differentiate into:
 TH1 cells
 TH2 cells
 TH17 cells
 Memory cells
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Figure 17.12 Activation of CD4+ T helper cells.
TH cell
receptor
(TCR)
Microorganism
carrying
antigens
Antigen
T helper
cell
Complex of MHC
class II molecule and
Antigen
MHC class II antigen fragment
fragments
molecules
(short peptides)
APC (dendritic cell)
An APC encounters and ingests a
microorganism. The antigen is enzymatically
processed into short peptides, which combine
with MHC class II molecules and are displayed
on the surface of the APC.
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Cytokines
Activated
T cell
Costimulatory molecule,
(required to activate T
cells that have not previously
encountered antigen)
A receptor (TCR) on the surface of the CD4+ T
helper cell (TH cell) binds to the MHC–antigen
complex. This includes a Toll-like receptor. The TH
cell or APC is stimulated to secrete a costimulatory
molecule. These two signals activate the TH cell,
which produces cytokines.
Activated T cells proliferate
The cytokines cause the TH cell
(which recognizes a dendritic cell
that is producing costimulatory
molecules) to become activated.
 TH17 cells produce IL-17 and contribute to
inflammation
 TH1 cells produce IFN-, which activates
macrophages, enhances complement, and stimulates
antibody production that promotes phagocytosis
 TH2 cells activate B cells to produce IgE; activate
eosinophils
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Figure 17.13 Lineage of effector T helper cell classes and pathogens targeted.
Antigen-presenting
cell
TH cells of various
classes
TH17 cells secrete cytokines that
promote inflammatory responses;
recruit neutrophils for protection
against extracellular bacteria
and fungi.
IL-17
IL-4
F-γ
TH1 cells are an important element of cellular
immunity. Their cytokines (such as IFN-γ and IL-2)
activate CD8+ T cells and NK cells, which control
intracellular pathogens by killing infected host
cells. They also enhance phagocytosis by
antigen-presenting cells such as macrophages.
TH2 cells
Fungi
Extracellular bacteria
Neutrophil
Macrophage
Mast cell
Basophil
Eosinophil
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Helminth
Important in allergic responses,
especially by production of IgE.
Activate eosinophils to control
extracellular parasites such as
helminths (see ADCC discussion).
Intracellular
bacteria and
protozoa
T Regulatory Cells (Treg)
 subset of CD4+ cells; carry an additional CD25
molecule
 suppress T cells against self; protect intestinal
bacteria required for digestion
 in pregnancy, they may play a role in protecting the fetus
from rejection as nonself
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T Cytotoxic Cells (CD8+ T Cells)
 Activated into cytotoxic T lymphocyte (CTL) with the
help of TH cell and costimulatory signals
 CTLs recognize and kill self-cells altered by infection
 Self-cells carry endogenous antigens on a surface
presented with MHC class I molecules
 CTL releases perforin and granzymes that induce
apoptosis in the infected cell
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Figure 17.14 Killing of virus-infected target cell by cytotoxic T lymphocyte.
Processed
antigen
MHC
class I
Processed antigen
presented with
MHC class I
Infected target
cell is lysed
T cell
receptors
Cytokines
CTL
CTLp
Virus-infected cell (example
of endogenous antigen)
Virus-infected cell
內源性抗原
A normal cell will not trigger a response
by a cytotoxic T lymphocyte (CTL), but a
virus-infected cell (shown here) or a cancer
cell produces abnormal endogenous antigens.
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TH1 cell
The abnormal antigen is presented on
the cell surface in association with MHC
class I molecules. Binding of a TH1 cell
promotes secretion of cytokines.
The cytokines
activate a precursor
CTL, which produces
a clone of CTLs.
The CTL induces
destruction of the
virus-infected cell by
apoptosis.
 Apoptosis
 Programmed cell death
 Prevents the spread of infectious viruses into other
cells
 Cells cut their genome into fragments, causing the
membranes to bulge outward via blebbing
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Figure 17.15 Apoptosis.
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Extracellular Killing by the Immune System
 Natural killer (NK) cells
 Granular leukocytes destroy cells that don't express
MHC class I self-antigens
 Kill virus-infected and tumor cells and attack parasites
 Not always stimulated by an antigen
 Form pores in the target cell, leading to lysis or
apoptosis
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Table 17.2 Principal Cells That Function in Cell-Mediated Immunity
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 Protozoans and helminths are too large to be
phagocytized
 Protozoan or helminth target cell is coated with antibodies
 Immune system cells attach to the Fc regions of
antibodies
 Target cell is lysed by chemicals secreted by the immune
system cell
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Figure 17.16 Antibody-dependent cell-mediated cytotoxicity (ADCC ).
KEY
Macrophage
Cytotoxic cytokines
Lytic enzymes
Perforin enzymes
Eosinophil
Extracellular
damage
Fc region
Large
parasite
Epitope
Antibody
Organisms, such as many parasites, that are too large for ingestion
by phagocytic cells must be attacked externally.
Fluke
Eosinophils
Eosinophils adhering to the larval stage of a
parasitic fluke
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Immunological Memory
 Secondary (memory or anamnestic) response
occurs after the second exposure to an antigen
 More rapid, lasts many days, greater in magnitude
 Memory cells produced in response to the initial
exposure are activated by the secondary exposure
 Antibody titer is the relative amount of antibody in the
serum
 Reflects intensity of the humoral response
 IgM is produced first, followed later by IgG
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Figure 17.17 The primary and secondary immune responses to an antigen.
IgG
Initial
exposure
to antigen
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IgM
Second
exposure
to antigen
Types of Adaptive Immunity
 Naturally acquired active immunity: resulting from
infection
 Naturally acquired passive immunity: transplacental
or via colostrum
 Artificially acquired active immunity: injection of Ag
(vaccination)
 Artificially acquired passive immunity: injection of Ab
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Figure 17.18 Types of adaptive immunity.
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Terminology
 Antiserum: blood-derived fluids containing antibodies
 Serology 血清學: the study of reactions between
antibodies and antigens
 Globulins: serum proteins
 Immunoglobulins: antibodies
 Gamma () globulin: serum fraction containing Ab
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Figure 17.19 The separation of serum proteins by gel electrophoresis.
Protein migration
Cathode
Trough
Anode
γ
β
Globulins
Globulins
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α
Albumin
Figure 17.20 The Dual Nature of the Adaptive Immune System.
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