Transcript Chapter 17

PowerPoint® Lecture
Presentations prepared by
Bradley W. Christian,
McLennan Community
College
CHAPTER
17
Adaptive
Immunity:
Specific
Defenses of
the Host
© 2016 Pearson Education, Inc.
© 2016 Pearson Education, Inc.
The Adaptive Immune System
Learning Objective
17-1 Compare and contrast adaptive and innate
immunity.
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The Adaptive Immune System
• Adaptive immunity: defenses that target a
specific pathogen
• 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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Host Defenses: The Big Picture
PLAY
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Animation: Host Defenses: The Big
Picture
Check Your Understanding
 Is vaccination an example of innate or adaptive
immunity?
17-1
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Dual Nature of the Adaptive Immune System
Learning Objective
17-2 Differentiate humoral from cellular immunity.
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Dual Nature of the Adaptive Immune System
• Humoral immunity
• Produces antibodies that combat foreign molecules
known as antigens
• B cells are lymphocytes that are created and mature in
red bone marrow
• Recognize antigens and make antibodies
• Named for bursa of Fabricius in birds
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Humoral Immunity: Overview
PLAY
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Animation: Humoral Immunity: Overview
Dual Nature of the Adaptive Immune System
• Cellular immunity (cell-mediated immunity)
• Produces T lymphocytes
• 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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Dual Nature of the Adaptive Immune System
• 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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Check Your Understanding
 What type of cell is most associated with humoral
immunity, and what type of cell is the basis of
cellular immunity?
17-2
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Cytokines: Chemical Messengers of Immune
Cells
Learning Objective
17-3 Identify at least one function of each of the
following: cytokines, interleukins, chemokines,
interferons, TNF, and hematopoietic cytokines.
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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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Check Your Understanding
 What is the function of cytokines?
17-3
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Antigens and Antibodies
Learning Objectives
17-4 Define antigen, epitope, and hapten.
17-5 Explain antibody function, and describe the
structural and chemical characteristics of
antibodies.
17-6 Name one function for each of the five classes
of antibodies.
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Antigens
• Antigens: substances that cause the production
of antibodies
• Usually components of invading microbes or foreign
substances
• Antibodies interact with epitopes, or antigenic
determinants, on the antigen
• Haptens: antigens too small to provoke immune
responses; attach to carrier molecules
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Figure 17.2 Epitopes (antigenic determinants).
Antibody A
Epitopes (antigenic determinants)
on antigen
Binding sites
Antigens:
components
of cell wall
Bacterial cell
Antibody B
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Figure 17.3 Haptens.
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Antibodies
• Globular proteins called immunoglobulins (Ig)
• Valence is the number of antigen-binding sites
on an antibody
• Bivalent antibodies have two binding sites
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Antibodies
• Four protein chains form a Y-shape
• Two identical light chains and two identical heavy
chains joined by disulfide links
• Variable (v) regions are at the ends of the arms;
bind epitopes
• Constant (Fc) region is the stem, which is identical
for a particular Ig class
• Five classes of Ig (IgG, IgM, IgA, IgD, IgE)
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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
IgG
•
•
•
•
Monomer
80% of serum antibodies
In the blood, lymph, and intestine
Cross the placenta; trigger complement; enhance
phagocytosis; neutralize toxins and viruses;
protect fetus
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IgM
• Pentamer made of five monomers held with a J
chain
• 6% of serum antibodies
• Remain in blood vessels
• Cause clumping of cells and viruses
• First response to an infection; short-lived
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IgA
• Monomer in serum; dimer in secretions
• 13% of serum antibodies
• Common in mucous membranes, saliva, tears,
and breast milk
• Prevent microbial attachment to mucous
membranes
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IgD
•
•
•
•
•
Monomer
0.02% of serum antibodies
Structure similar to IgG
In blood, in lymph, and on B cells
No well-defined function; assists in the immune
response on B cells
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IgE
•
•
•
•
Monomer
0.002% of serum antibodies
On mast cells, on basophils, and in blood
Cause the release of histamines when bound to
antigen; lysis of parasitic worms
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Table 17.1 A Summary of Immunoglobulin Classes
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Check Your Understanding
 Does an antibody react with a bacterium as an
antigen or as an epitope?
17-4
 The original theoretical concepts of an antibody
called for a rod with antigenic determinants at
each end. What is the primary advantage of the
Y-shaped structure that eventually emerged?
17-5
 Which class of antibody is most likely to protect
you from a common cold?
17-6
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Humoral Immunity Response Process
Learning Objectives
17-7 Compare and contrast T-dependent and
T-independent antigens.
17-8 Differentiate plasma cell from memory cell.
17-9 Describe clonal selection.
17-10 Describe how a human can produce different
antibodies.
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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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Clonal Selection of Antibody-Producing Cells
• 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.
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.
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Antigen is
internalized into
the B cell.
Fragments of the
antigen are presented
on MHC proteins on
the surface of the cell.
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 of Antibody-Producing 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.
Clonal Selection of Antibody-Producing Cells
• T-dependent antigen
• Antigen that requires a TH cell to produce antibodies
• T-independent antigens
• 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 Processing and Presentation: Overview
PLAY
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Animation: Antigen Processing and
Presentation: Overview
Humoral Immunity: Clonal Selection and
Expansion
PLAY
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Animation: Humoral Immunity: Clonal
Selection and Expansion
Check Your Understanding
 Would pneumococcal pneumonia (see
Figure 24.12, page 689) require a TH cell to
stimulate a B cell to form antibodies?
17-7
 Plasma cells produce antibodies; do they also
produce memory cells?
17-8
 In what way does a B cell that encounters an
antigen function as an antigen-presenting cell?
17-9
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Check Your Understanding
 On what part of the antibody molecule do we find
the amino acid sequence that makes the huge
genetic diversity of antibody production possible?
17-10
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Antigen–Antibody Binding and Its Results
Learning Objective
17-11 Describe four outcomes of an
antigen–antibody reaction.
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Antigen–Antibody Binding and Its Results
• 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
Reduces number of infectious
units to be dealt with
Activation of complement
Causes inflammation and cell lysis
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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Humoral Immunity: Antibody Function
PLAY
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Animation: Humoral Immunity: Antibody
Function
Check Your Understanding
 Which antibodies may activate the complement
system, and which antibodies are usually
associated with agglutination?
17-11
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Cellular Immunity Response Process
Learning Objectives
17-12 Describe at least one function of each of the
following: M cells, TH cells, TC cells, CTLs,
Treg cells, NK cells.
17-13 Differentiate T helper, T cytotoxic, and
T regulatory cells.
17-14 Differentiate TH1, TH2, and TH17 cells.
17-15 Define apoptosis.
17-16 Define antigen-presenting cell.
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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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Cellular Immunity Response Process
• 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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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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Antigen Processing and Presentation: MHC
PLAY
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Animation: Antigen Processing and
Presentation: MHC
Classes of T Cells
• Clusters of differentiation (CD)
• 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:
•
•
•
•
TH1cells
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.
T Helper Cells (CD4+ T Cells)
• TH17 cells produce IL-17 and contribute to
inflammation
• TH1 cells produce IFN-g, 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
IFN-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
Antigen Processing and Presentation: Steps
PLAY
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Animation: Antigen Processing and
Presentation: Steps
T Regulatory Cells
• T regulatory cells (Treg)
• Subset of CD4+ cells; carry an additional CD25
molecule
• Suppress T cells against self; protect intestinal
bacteria required for digestion; protect fetus
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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
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.
T Cytotoxic Cells (CD8+ T Cells)
• 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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Cell-Mediated Immunity: Cytotoxic T Cells
PLAY
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Animation: Cell-Mediated Immunity:
Cytotoxic T Cells
Check Your Understanding
 Which antibody is the primary one produced when
an antigen is taken up by an M cell?
17-12
 Which T cell type is generally involved when a
B cell reacts with an antigen and produces
antibodies against the antigen?
17-13
 Which T cell type is generally involved in allergic
reactions?
17-14
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Check Your Understanding
 What is another name for apoptosis, one that
describes its function?
17-15
 Are dendritic cells considered primarily part of the
humoral or the cellular immune system?
17-16
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Extracellular Killing by the Immune System
Learning Objective
17-17 Describe the function of natural killer cells.
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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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Check Your Understanding
 How does the natural killer cell respond if the
target cell does not have MHC class I molecules
on its surface?
17-17
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Antibody-Dependent Cell-Mediated Cytotoxicity
Learning Objective
17-18 Describe the role of antibodies and natural
killer cells in antibody-dependent cellmediated cytotoxicity.
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Antibody-Dependent Cell-Mediated Cytotoxicity
• 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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Check Your Understanding
 What makes a natural killer cell, which is not
immunologically specific, attack a particular target
cell?
17-18
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Immunological Memory
Learning Objective
17-19 Distinguish a primary from a secondary
immune response.
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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
Humoral Immunity: Primary Immune Response
PLAY
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Animation: Humoral Immunity: Primary
Immune Response
Humoral Immunity: Secondary Immune
Response
PLAY
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Animation: Humoral Immunity: Secondary
Immune Response
Check Your Understanding
 Is the anamnestic response primary or
secondary?
17-19
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Types of Adaptive Immunity
Learning Objective
17-20 Contrast the four types of adaptive immunity.
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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 vaccination (immunization)
• Artificially acquired passive immunity
• Injection of antibodies
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Figure 17.18 Types of adaptive immunity.
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Types of Adaptive Immunity
• Antiserum: blood-derived fluids containing
antibodies
• Serology: the study of reactions between
antibodies and antigens
• Globulins: serum proteins
• Gamma (g) globulin: serum fraction containing
antibodies
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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
Check Your Understanding
 What type of adaptive immunity is involved when
gamma globulin is injected into a person?
17-20
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Figure 17.20 The Dual Nature of the Adaptive Immune System.
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