Download Activation of B Cells

Chapter 17
Functional
Anatomy of
Prokaryotic and
Eukaryotic Cells
© 2013 Pearson Education, Inc.
Lectures prepared by Christine L. Case
The Adaptive Immune System
Learning Objectives
17-1 Differentiate innate from adaptive immunity.
17-2 Differentiate humoral from cellular immunity.
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Immunity
ƒ Innate immunity: defenses against any pathogen
ƒ Adaptive immunity: induced resistance to a
specific pathogen
ANIMATION Host Defenses: The Big Picture
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Historical Development
ƒ Pasteur observed immunity in chickens injected
with weakened pathogens
ƒ Von Behring received the Nobel prize for
development of antitoxin
ƒ Ehrlich’s work led to the identification of antibodies
in serum
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Dual Nature of Adaptive Immunity
ƒ T and B cells develop from stem cells in red bone
marrow
Figure 17.8 Differentiation of T cells and B cells.
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Dual Nature of Adaptive Immunity
ƒ Humoral immunity
ƒ Due to antibodies
ƒ B cells mature in the bone marrow
− Chickens: bursa of Fabricius
ƒ Cellular immunity
ƒ Due to T cells
ƒ T cells mature in the thymus
ANIMATION Humoral Immunity: Overview
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Antigens and Antibodies
Learning Objectives
17-3 Define antigen, epitope, and hapten.
17-4 Explain the function of antibodies, and describe
their structural and chemical characteristics.
17-5 Name one function for each of the five classes
of antibodies.
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The Nature of Antigens
ƒ Antigen (Ag): a substance that causes the body to
produce specific antibodies or sensitized T cells
ƒ Antibodies (Ab) interact with epitopes, or antigenic
determinants
ƒ Hapten: antigen is combined with carrier
molecules
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Antigens
Figure 17.1 Epitopes (antigenic determinants).
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Haptens
Figure 17.2 Haptens.
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The Nature of Antibodies
ƒ Globular proteins called immunoglobulins
ƒ The number of antigen-binding sites determines
valence
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Antibodies
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tc
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Antigenbinding
site
Fc (stem) region
Hinge
region
Antibody molecule
Epitope
(antigenic
determinant)
Antigen
Antigenbinding site
Enlarged antigen-binding site bound to an epitope
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Figure 17.3ab The structure of a typical antibody molecule.
Antibodies
Antibodies
Antibody molecules shown by atomic
force microscopy (see page 64)
Figure 17.3c The structure of a typical antibody molecule.
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IgG Antibodies
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
Monomer
80% of serum antibodies
Fix complement
In blood, lymph, and intestine
Cross placenta
Enhance phagocytosis; neutralize toxins and
viruses; protect fetus and newborn
ƒ Half-life = 23 days
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IgM Antibodies
ƒ
ƒ
ƒ
ƒ
ƒ
Pentamer
5–10% of serum antibodies
Fix complement
In blood, in lymph, and on B cells
Agglutinate microbes; first Ab produced in
response to infection
ƒ Half-life = 5 days
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IgA Antibodies
ƒ
ƒ
ƒ
ƒ
ƒ
Dimer
10–15% of serum antibodies
In secretions
Mucosal protection
Half-life = 6 days
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IgD Antibodies
ƒ
ƒ
ƒ
ƒ
ƒ
Monomer
0.2% of serum antibodies
In blood, in lymph, and on B cells
On B cells, initiate immune response
Half-life = 3 days
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IgE Antibodies
ƒ
ƒ
ƒ
ƒ
ƒ
Monomer
0.002% of serum antibodies
On mast cells, on basophils, and in blood
Allergic reactions; lysis of parasitic worms
Half-life = 2 days
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B Cells and Humoral Immunity
Learning Objectives
17-6 Compare and contrast T-dependent and
T-independent antigens.
17-7 Differentiate plasma cell from memory cell.
17-8 Describe clonal selection.
17-9 Describe how a human can produce different
antibodies.
17-10 Describe four outcomes of an antigen–antibody
reaction.
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Activation of B Cells
ƒ Major histocompatibility complex (MHC)
expressed on mammalian cells
ƒ T-dependent antigens
ƒ Ag presented with (self) MHC to TH cell
ƒ TH cell produces cytokines that activate the B cell
ƒ T-independent antigens
ƒ Stimulate the B cell to make Abs
ANIMATION Antigen Processing and Presentation: Overview
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Activation of B Cells
Figure 17.6 T-independent antigens.
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Activation of B Cells
Extracellular
antigens
Ag fragment
MHC class II with
Ag fragment
MHC class II
with Ag
fragment
displayed on
surface
Antibodies
B cell
B cell
B cell
Immunoglobulin
receptors
coating
B cell surface
Immunoglobulin receptors
on B cell surface recognize
and attach to antigen,
which is then internalized
and processed. Within the
B cell a fragment of the
antigen combines with
MHC class II.
Plasma cell
TH cell
Cytokines
MHC class II–antigenfragment complex is
displayed on B cell
surface.
Receptor on the T helper cell
(TH) recognizes complex of
MHC class II and antigen
fragment and is activated—
producing cytokines, which
activate the B cell. The TH cell
has been previously activated by
an antigen displayed on a
dendritic cell (see Figure 17.10).
B cell is activated by
cytokines and begins
clonal expansion. Some
of the progeny become
antibody-producing
plasma cells.
Figure 17.4 Activation of B cells to produce antibodies.
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Clonal Selection
ANIMATION Humoral Immunity: Clonal Selection and Expansion
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Activation of B Cells
ƒ B cells differentiate into:
ƒ Antibody-producing plasma cells
ƒ Memory cells
ƒ Clonal deletion eliminates harmful B cells
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Antigen–Antibody Binding
ƒ Agglutination
ƒ Opsonization
ƒ Activation of complement
ƒ Antibody-dependent cell-mediated cytotoxicity
ƒ Neutralization
ANIMATION Humoral Immunity: Antibody Function
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The Results of Ag-Ab Binding
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Figure 17.7 The results of antigen–antibody binding.
T Cells and Cellular Immunity
Learning Objectives
17-11 Describe at least one function of each of the
following: M cells, TH cells, TC cells, Treg cells,
CTLs, NK cells.
17-12 Differentiate T helper, T cytotoxic, and
T regulatory cells.
17-13 Differentiate TH1, TH2, and TH17 cells.
17-14 Define apoptosis.
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T Cells and Cellular Immunity
ƒ T cells mature in the thymus
ƒ Thymic selection eliminates many immature T cells
ƒ T cells respond to Ag by T-cell receptors (TCRs)
ƒ T cells require antigen-presenting cells (APCs)
ƒ Pathogens entering the gastrointestinal or
respiratory tracts pass through
ƒ M (microfold) cells over
ƒ Peyer’s patches, which contain APCs
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M Cells on Peyer’s Patch
Figure 17.9 M cells.
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M Cells
ANIMATION Cell-Mediated Immunity: Overview
Figure 17.9 M cells.
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T Helper Cells
ƒ CD4+ or TH cells
ƒ TCRs recognize Ags and MHC II on APC
ƒ TLRs are a costimulatory signal on APC and TH
ƒ TH cells produce cytokines and differentiate into:
− TH1cells
− TH2 cells
− TH17 cells
− Memory cells
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T Helper Cells
ƒ TH1 produce IFN-γ, which activates cells related to
cell-mediated immunity, macrophages, and Abs
ƒ TH2 activate eosinophils and B cells to produce IgE
ƒ TH17 stimulate the innate immune system
ƒ TF stimulate B cells to produce plasma cells and
are involved in class switching
ANIMATION Antigen Processing and Presentation: Steps
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Antibodies
B cell
TH1 cells
TH2 cells
Recruits neutrophils; provides
protection against extracellular
bacteria and fungi
TH17 cells
TH cell
IL-17
IL-4
TH17 cells
Cell-mediated immunity; control
of intracellular pathogens, delayed
hypersensitivity reactions (page 535);
stimulates macrophages.
IFN-γ
TH1 cells
TH2 cells
Fungi
Extracellular
bacteria
Neutrophil
Macrophage
Mast cell
Basophil
Eosinophil
Intracellular bacteria
and protozoa
Important in allergic
responses, especially by
production of IgE
Stimulates activity of
eosinophils to control
extracellular parasites
such as helminths (see
ADCC, page 495).
Helminth
Figure 17.11 Lineage of effector T helper cell classes and pathogens targeted.
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Activation of CD4+ T Helper Cells
Figure 17.10 Activation of CD4+T helper cells.
ANIMATION Cell-Mediated Immunity: Helper T Cells
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T Cytotoxic Cells
ƒ CD8+ or TC cells
ƒ Target cells are self-cells carrying endogenous
antigens
ƒ Activated into cytotoxic T lymphocytes (CTLs)
ƒ CTLs recognize Ag + MHC I
ƒ Induce apoptosis in target cell
ƒ CTL releases perforin and granzymes
ANIMATION Cell-Mediated Immunity: Cytotoxic T Cells
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T Cytotoxic Cells
Figure 17.12 Killing of virus-infected target cell by cytotoxic T lymphocyte.
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Apoptosis
Figure 17.13 Apoptosis.
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T Regulatory Cells
ƒ Treg cells
ƒ CD4 and CD25 on surface
ƒ Suppress T cells against self
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T Cells and Cellular Immunity
Learning Objectives
17-15 Define antigen-presenting cell.
17-16 Describe the function of natural killer cells.
17-17 Describe the role of antibodies and natural
killer cells in antibody-dependent cell-mediated
cytotoxicity.
17-18 Identify at least one function of each of the
following: cytokines, interleukins, chemokines,
interferons, TNF, and hematopoietic cytokines.
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Antigen-Presenting Cells
ƒ Digest antigen
ƒ Ag fragments on APC surface with MHC
ƒ B cells
ƒ Dendritic cells
ƒ Activated macrophages
ANIMATION Antigen Processing and Presentation: MHC
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Figure 17.14 A dendritic cell.
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Activated
macrophages
Resting (inactive)
macrophage
Figure 17.15 Activated macrophages.
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Natural Killer (NK) Cells
ƒ Granular leukocytes destroy cells that don’t
express MHC I
ƒ Kill virus-infected and tumor cells
ƒ Attack parasites
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ADCC
ƒ Antibody-dependent cell-mediated cytotoxicity
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ADCC
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Figure 17.16 Antibody-dependent cell-mediated cytotoxicity (ADCC).
Cytokines
ƒ Chemical messengers
ƒ Overproduction leads to cytokine storm
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Cells Communicate via Cytokines
Cytokine
Representative Activity
Interleukin-1 (IL-1)
Stimulates TH cells in presence of
antigens; attracts phagocytes
Interleukin-2 (IL-2)
Proliferation of antigen-stimulated
CD4+ T helper cells, proliferation
and differentiation of B cells;
activation of CD8+ T cells and NK
cells
Interleukin-12 (IL-12)
Inhibits humoral immunity;
activates TH1 cellular immunity
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Cells Communicate via Cytokines
Cytokine
Representative Activity
Chemokines
Induce the migration of leukocytes
TNF-α
Promotes inflammation
Hematopoietic
cytokines
Influence differentiation of blood
stem cells
IFN-α and IFN-β
Response to viral infection;
interfere with protein synthesis
IFN-γ
Stimulates macrophage activity
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T Cells and Cellular Immunity
Learning Objectives
17-19 Distinguish a primary from a secondary
immune response.
17-20 Contrast the four types of adaptive
immunity.
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Immunological Memory
ƒ Antibody titer is the amount of Ab in serum
ƒ Primary response occurs after initial contact
with Ag
ƒ Secondary (memory or anamnestic)
response occurs after second exposure
ANIMATION Humoral Immunity: Primary Immune Response
ANIMATION Humoral Immunity: Secondary Immune Response
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Immune Responses to an Antigen
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Figure 17.17 The primary and secondary immune responses to an antigen.
Types of Adaptive Immunity
ƒ Naturally acquired active immunity
ƒ Resulting from infection
ƒ Naturally acquired passive immunity
ƒ Transplacental or via colostrum
ƒ Artificially acquired active immunity
ƒ Injection of Ag (vaccination)
ƒ Artificially acquired passive immunity
ƒ Injection of Ab
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Figure 17.18
Terminology of Adaptive Immunity
ƒ Serology: the study of reactions between
antibodies and antigens
ƒ Antiserum: the generic term for serum because it
contains Ab
ƒ Globulins: serum proteins
ƒ Immunoglobulins: antibodies
ƒ Gamma (γ) globulin: serum fraction containing Ab
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Serum Proteins
Figure 17.19 The separation of serum proteins by gel electrophoresis.
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Figure 17.20 The dual nature of the adaptive immune system.
Humoral (antibody-mediated) immune system
Cellular (cell-mediated) immune system
Control of freely circulating pathogens
Control of intracellular pathogens
Check Your Understanding
Intracellular antigens are
expressed on the surface of an
APC, a cell infected by a virus, a
bacterium, or a parasite.
Extracellular antigens
A B cell binds to the
antigen for which it is
specific. A T-dependent B
cell requires cooperation
with a T helper (TH) cell.
T cell
Cytokines activate T
helper (TH) cell.
Cytokines activate
macrophage.
Cytokines
Cytokines
B cell
The B cell, often with
stimulation by cytokines
from a TH cell, differentiates
into a plasma cell. Some B
cells become memory cells.
Cytokines from the TH
cell transform B cells
into antibody-producing
plasma cells.
Plasma cells
proliferate and
produce antibodies
against the antigen.
Activation of
macrophage
(enhanced
phagocytic activity).
TH cell
Cytotoxic T
lymphocyte
Plasma cell
Memory cell
Some T and B cells differentiate
into memory cells that respond
rapidly to any secondary
encounter with an antigen.
Lysed target cell
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A T cell binds to
MHC–antigen
complexes on the
surface of the
infected cell,
activating the T cell
(with its cytokine
receptors).
The CD8+T cell
becomes a cytotoxic
T lymphocyte (CTL)
able to induce
apoptosis of the
target cell.