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Janice Meeking,
Mount Royal College
CHAPTER
21
The Immune
System:
Innate and
Adaptive Body
Defenses:
Part B
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Antibodies
• Immunoglobulins—gamma globulin portion of
blood
• Proteins secreted by plasma cells
• Capable of binding specifically with antigen
detected by B cells
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Basic Antibody Structure
• T-or Y-shaped monomer of four looping linked
polypeptide chains
• Two identical heavy (H) chains and two
identical light (L) chains
• Variable (V) regions of each arm combine to
form two identical antigen-binding sites
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Basic Antibody Structure
• Constant (C) region of stem determines
• The antibody class (IgM, IgA, IgD, IgG, or IgE)
• The cells and chemicals that the antibody can
bind to
• How the antibody class functions in antigen
elimination
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Antigen-binding
site
Heavy chain
variable region
Heavy chain
constant region
Light chain
variable region
Light chain
constant region
Disulfide bond
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Hinge
region
Stem
region
(a)
Figure 21.14a
Classes of Antibodies
• IgM
• A pentamer; first antibody released
• Potent agglutinating agent
• Readily fixes and activates complement
• IgA (secretory IgA)
• Monomer or dimer; in mucus and other
secretions
• Helps prevent entry of pathogens
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Table 21.3
Classes of Antibodies
• IgD
• Monomer attached to the surface of B cells
• Functions as a B cell receptor
• IgG
• Monomer; 75–85% of antibodies in plasma
• From secondary and late primary responses
• Crosses the placental barrier
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Classes of Antibodies
• IgE
• Monomer active in some allergies and
parasitic infections
• Causes mast cells and basophils to release
histamine
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Table 21.3
Generating Antibody Diversity
• Billions of antibodies result from somatic
recombination of gene segments
• Hypervariable regions of some genes
increase antibody variation through somatic
mutations
• Each plasma cell can switch the type of H
chain produced, making an antibody of a
different class
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Antibody Targets
• Antibodies inactivate and tag antigens
• Form antigen-antibody (immune) complexes
• Defensive mechanisms used by antibodies
• Neutralization and agglutination (the two most
important)
• Precipitation and complement fixation
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Neutralization
• Simplest mechanism
• Antibodies block specific sites on viruses or
bacterial exotoxins
• Prevent these antigens from binding to
receptors on tissue cells
• Antigen-antibody complexes undergo
phagocytosis
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Agglutination
• Antibodies bind the same determinant on
more than one cell-bound antigen
• Cross-linked antigen-antibody complexes
agglutinate
• Example: clumping of mismatched blood cells
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Precipitation
• Soluble molecules are cross-linked
• Complexes precipitate and are subject to
phagocytosis
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Complement Fixation and Activation
• Main antibody defense against cellular
antigens
• Several antibodies bind close together on a
cellular antigen
• Their complement-binding sites trigger
complement fixation into the cell’s surface
• Complement triggers cell lysis
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Complement Fixation and Activation
• Activated complement functions
• Amplifies the inflammatory response
• Opsonization
• Enlists more and more defensive elements
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Adaptive defenses
Humoral immunity
Antigen
Antigen-antibody
complex
Antibody
Inactivates by
Neutralization
(masks dangerous
parts of bacterial
exotoxins; viruses)
Agglutination
(cell-bound antigens)
Enhances
Phagocytosis
Fixes and activates
Precipitation
(soluble antigens)
Enhances
Complement
Leads to
Inflammation
Cell lysis
Chemotaxis
Histamine
release
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Figure 21.15
Cell-Mediated Immune Response
• T cells provide defense against intracellular
antigens
• Two types of surface receptors of T cells
• T cell antigen receptors
• Cell differentiation glycoproteins
• CD4 or CD8
• Play a role in T cell interactions with other
cells
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Cell-Mediated Immune Response
• Major types of T cells
• CD4 cells become helper T cells (TH) when
activated
• CD8 cells become cytotoxic T cells (TC) that
destroy cells harboring foreign antigens
• Other types of T cells
• Regulatory T cells (TREG)
• Memory T cells
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Adaptive defenses
Cellular immunity
Immature
lymphocyte
Red bone marrow
T cell
receptor
Class II MHC
protein
T cell
receptor
Maturation
CD4
cell
Thymus
Activation
APC
(dendritic cell)
Activation
Memory
cells
CD4
Class I MHC
protein
CD8
cell
APC
(dendritic cell)
CD8
Lymphoid
tissues and
organs
Helper T cells
(or regulatory T cells)
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Effector
cells
Blood plasma
Cytotoxic T cells
Figure 21.16
Comparison of Humoral and Cell-Mediated
Response
• Antibodies of the humoral response
• The simplest ammunition of the immune
response
• Targets
• Bacteria and molecules in extracellular
environments (body secretions, tissue fluid,
blood, and lymph)
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Comparison of Humoral and Cell-Mediated
Response
• T cells of the cell-mediated response
• Recognize and respond only to processed
fragments of antigen displayed on the surface
of body cells
• Targets
• Body cells infected by viruses or bacteria
• Abnormal or cancerous cells
• Cells of infused or transplanted foreign tissue
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Antigen Recognition
• Immunocompetent T cells are activated when
their surface receptors bind to a recognized
antigen (nonself)
• T cells must simultaneously recognize
• Nonself (the antigen)
• Self (an MHC protein of a body cell)
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MHC Proteins
• Two types of MHC proteins are important to T
cell activation
• Class I MHC proteins - displayed by all cells
except RBCs
• Class II MHC proteins – displayed by APCs
(dendritic cells, macrophages and B cells)
• Both types are synthesized at the ER and
bind to peptide fragments
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Class I MHC Proteins
• Bind with fragment of a protein synthesized in
the cell (endogenous antigen)
• Endogenous antigen is a self-antigen in a
normal cell; a nonself antigen in an infected or
abnormal cell
• Informs cytotoxic T cells of the presence of
microorganisms hiding in cells (cytotoxic T
cells ignore displayed self-antigens)
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Cytoplasm of any tissue cell
2 Endogenous antigen
1 Endogenous
peptides enter ER via
antigen is degraded
transport protein.
by protease.
Endogenous antigen—
self-protein or foreign
(viral or cancer) protein
Cisternae of
endoplasmic
reticulum (ER)
3 Endogenous
antigen peptide is
loaded onto class
I MHC protein.
4 Loaded MHC protein
migrates in vesicle to
the plasma membrane,
where it displays the
antigenic peptide.
Transport
protein
(ATPase)
Plasma membrane of a tissue cell
Antigenic peptide
Extracellular fluid
(a) Endogenous antigens are processed and displayed on class I MHC of all cells.
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Figure 21.17a
Class II MHC Proteins
• Bind with fragments of exogenous antigens
that have been engulfed and broken down in
a phagolysosome
• Recognized by helper T cells
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Cytoplasm of APC
1a
Class II MHC is
synthesized in ER.
Invariant chain
prevents class II
MHC from binding
to peptides in the ER.
3
Vesicle fuses with
phagolysosome. Invariant
chain is removed, and
antigen is loaded.
2a
Cisternae of
endoplasmic
Phagosome
reticulum (ER)
1b Extracellular
antigen (bacterium)
is phagocytized.
Class II MHC
is exported
from ER in a
vesicle.
4
Vesicle with
loaded MHC
migrates to the
plasma
membrane.
2b
Phagosome merges
with lysosome, forming
a phagolysosome;
antigen is degraded.
Extracellular
antigen
Extracellular fluid
Lysosome
Plasma membrane of APC
Antigenic peptide
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
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Figure 21.17b
T Cell Activation
•
APCs (most often a dendritic cell) migrate to
lymph nodes and other lymphoid tissues to
present their antigens to T cells
•
T cell activation is a two-step process
1. Antigen binding
2. Co-stimulation
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T Cell Activation: Antigen Binding
• CD4 and CD8 cells bind to different classes of
MHC proteins (MHC restriction)
• CD4 cells bind to antigen linked to class II
MHC proteins of APCs
• CD8 cells are activated by antigen fragments
linked to class I MHC of APCs
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T Cell Activation: Antigen Binding
• Dendritic cells are able to obtain other cells’
endogenous antigens by
• Engulfing dying virus-infected or tumor cells
• Importing antigens through temporary gap
junctions with infected cells
• Dendritic cells then display the endogenous
antigens on both class I and class II MHCs
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T Cell Activation: Antigen Binding
• TCR that recognizes the nonself-self complex
is linked to multiple intracellular signaling
pathways
• Other T cell surface proteins are involved in
antigen binding (e.g., CD4 and CD8 help
maintain coupling during antigen recognition)
• Antigen binding stimulates the T cell, but costimulation is required before proliferation can
occur
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Adaptive defenses
Cellular immunity
1 Dendritic cell
Viral antigen
Dendritic
cell
T cell receptor
(TCR)
Clone
formation
Class lI MHC
protein
displaying
processed
viral antigen
CD4 protein
engulfs an
exogenous antigen,
processes it, and
displays its
fragments on class
II MHC protein.
2 Immunocompetent
CD4 cell recognizes
antigen-MHC
complex. Both TCR
and CD4 protein bind
Immunocom- to antigen-MHC
complex.
petent CD4
T cell
3 CD4 cells are
activated,
proliferate (clone),
and become memory
and effector cells.
Helper T
memory cell
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Activated
helper
T cells
Figure 21.18
T Cell Activation: Co-Stimulation
• Requires T cell binding to other surface receptors on
an APC
• Cytokines (interleukin 1 and 2 from APCs or T cells)
trigger proliferation and differentiation of activated T
cell
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T Cell Activation: Co-Stimulation
• Without co-stimulation, anergy occurs
• T cells
• Become tolerant to that antigen
• Are unable to divide
• Do not secrete cytokines
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T Cell Activation: Co-Stimulation
• T cells that are activated
• Enlarge, proliferate, and form clones
• Differentiate and perform functions according
to their T cell class
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Cytokines
• Mediate cell development, differentiation, and
responses in the immune system
• Include interleukins and interferons
• Interleukin 1 (IL-1) released by macrophages
co-stimulates bound T cells to
• Release interleukin 2 (IL-2)
• Synthesize more IL-2 receptors
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Cytokines
• IL-2 is a key growth factor, acting on cells that
release it and other T cells
• Encourages activated T cells to divide rapidly
• Used therapeutically to treat melanoma and
kidney cancers
• Other cytokines amplify and regulate innate
and adaptive responses
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Roles of Helper T(TH) Cells
• Play a central role in the adaptive immune response
• Once primed by APC presentation of antigen, they
• Help activate T and B cells
• Induce T and B cell proliferation
• Activate macrophages and recruit other immune cells
• Without TH, there is no immune response
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Helper T Cells
• Interact directly with B cells displaying antigen
fragments bound to MHC II receptors
• Stimulate B cells to divide more rapidly and
begin antibody formation
• B cells may be activated without TH cells by
binding to T cell–independent antigens
• Most antigens require TH co-stimulation to
activate B cells
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TH cell help in humoral immunity
Activated helper
T cell
1 TH cell binds with the
Helper T cell
CD4 protein
self-nonself complexes of a
B cell that has encountered
its antigen and is displaying
it on MHC II on its surface.
MHC II protein
of B cell displaying
processed antigen
2 TH cell releases
T cell receptor (TCR)
IL- 4 and other
cytokines
interleukins as
co-stimulatory signals to
complete B cell activation.
B cell (being activated)
(a)
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Figure 21.19a
Roles of Cytotoxic T(TC) Cells
• Directly attack and kill other cells
• Activated TC cells circulate in blood and lymph
and lymphoid organs in search of body cells
displaying antigen they recognize
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Roles of Cytotoxic T(TC) Cells
• Targets
• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells (transfusions or transplants)
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Cytotoxic T Cells
• Bind to a self-nonself complex
• Can destroy all infected or abnormal cells
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