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prepared by
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
• Two identical heavy (H) chains and two
identical light (L) chains
• Variable (V) regions: two identical antigenbinding sites
• Constant (C) region of stem determines
• The antibody class (IgM, IgA, IgD, IgG, or IgE)
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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
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Table 21.3
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Table 21.3
Classical pathway
Antigen-antibody complex
+
complex
Opsonization:
coats pathogen
surfaces, which
enhances phagocytosis
Insertion of MAC and cell lysis
(holes in target cell’s membrane)
Alternative pathway
Spontaneous activation
+
Stabilizing factors (B, D, and P)
+
No inhibitors on pathogen
surface
Enhances inflammation:
stimulates histamine release,
increases blood vessel
permeability, attracts
phagocytes by chemotaxis,
etc.
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
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Figure 21.6
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
1. Neutralization
2. Agglutination (1 and 2 most important)
3. Precipitation
4. Complement fixation
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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 by MHC II
• CD8 cells become cytotoxic T cells (TC) when
activated by MHC I destroy cells harboring
foreign antigens
• Other types of T cells
• Regulatory T cells (TREG)
• Memory T cells
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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
• MHC I (CD8) and MHC II (APC + CD4)
• Targets
1. Body cells infected by viruses or bacteria
2. Abnormal or cancerous cells
3. Cells of infused or transplanted foreign tissue
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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)
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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 non-self 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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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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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
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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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
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 or 4) 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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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
Figure 21.19b The central role of helper T cells in mobilizing both humoral and cellular immunity.
TH cell help in cell-mediated immunity
CD4 protein
Helper T cell
Class II MHC
protein
APC (dendritic cell)
1 Previously
activated TH cell
binds dendritic cell.
2 TH cell stimulates
IL-2
dendritic cell to express
co-stimulatory
molecules (not shown)
needed to activate CD8
cell.
3 Dendritic cell can
Class I
MHC protein
(b)
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CD8
protein
CD8 T cell
now activate CD8 cell
with the help of
interleukin 2 secreted
by TH cell.
Roles of Cytotoxic T (TC or 8) 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)
• Bind to a self-nonself complex
• Can destroy all infected or abnormal cells
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Figure 21.19 The central role of helper T cells in mobilizing both humoral and cellular immunity.
Humoral immunity
Cellular immunity
Adaptive defenses
Activated helper
T cell
1 T cell binds with the
H
self-nonself complexes of a
B cell that has encountered
its antigen and is displaying
it on MHC II on its surface.
T cell receptor (TCR)
Helper T cell
CD4 protein
MHC II protein
of B cell displaying
processed antigen
2 TH cell releases
interleukins as
co-stimulatory signals to
complete B cell activation.
IL- 4 and other
cytokines
B cell (being activated)
(a)
TH cell help in cell-mediated immunity
CD4 protein
Helper T cell
1 Previously activated T
H
cell binds dendritic cell.
Class II MHC
protein
APC (dendritic cell)
IL-2
2 TH cell stimulates dendritic
cell to express co-stimulatory
molecules (not shown) needed
to activate CD8 cell.
3 Dendritic cell can now
Class I
MHC protein
(b)
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CD8
protein
CD8 T cell
activate CD8 cell with the
help of interleukin 2 secreted
by TH cell.
Figure 21.20a Cytotoxic T cells attack infected and cancerous cells.
Adaptive defenses
Cytotoxic
T cell (TC)
Cellular immunity
1 TC binds tightly to
the target cell when it
identifies foreign antigen
on MHC I proteins.
granzyme molecules from its
granules by exocytosis.
Granule
Perforin
3 Perforin molecules
insert into the target
cell membrane,
polymerize, and form
transmembrane pores
(cylindrical holes)
similar to those
produced by
complement
activation.
TC cell
membrane
Target
cell
membrane
Target
cell
2 TC releases perforin and
4 Granzymes enter the
Perforin
pore
Granzymes
5 The TC detaches and
target cell via the pores.
Once inside, these
proteases degrade
cellular contents,
stimulating apoptosis.
searches for another prey.
(a) A mechanism of target cell killing by TC cells.
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Table 21.1 Inflammatory Chemicals
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Table 21.2 Summary of Innate Body Defenses (1 of 2)
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Table 21.2 Summary of Innate Body Defenses (2 of 2)
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Table 21.3 Immunoglobulin Classes (1 of 2)
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Table 21.3 Immunoglobulin Classes (2 of 2)
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Table 21.4 Selected Cytokines
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Table 21.5 Cells and Molecules of the Adaptive Immune Response (1 of 2)
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Table 21.5 Cells and Molecules of the Adaptive Immune Response (2 of 2)
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