Download Chapter 21 PowerPoint

PowerPoint® Lecture Slides
prepared by
Janice Meeking,
Mount Royal College
CHAPTER
21
The Immune
System:
Innate and
Adaptive Body
Defenses:
Part B
Copyright © 2010 Pearson Education, Inc.
Antibodies
• Immunoglobulins—gamma globulin portion of
blood
• Proteins secreted by plasma cells
• Capable of binding specifically with antigen
detected by B cells
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Antigen-binding
site
Heavy chain
variable region
Heavy chain
constant region
Light chain
variable region
Light chain
constant region
Disulfide bond
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Classes of Antibodies
• IgE
• Monomer active in some allergies and
parasitic infections
• Causes mast cells and basophils to release
histamine
Copyright © 2010 Pearson Education, Inc.
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Precipitation
• Soluble molecules are cross-linked
• Complexes precipitate and are subject to
phagocytosis
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Complement Fixation and Activation
• Activated complement functions
• Amplifies the inflammatory response
• Opsonization
• Enlists more and more defensive elements
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Figure 21.15
Monoclonal Antibodies
• Commercially prepared pure antibody
• Produced by hybridomas
• Cell hybrids: fusion of a tumor cell and a B cell
• Proliferate indefinitely and have the ability to
produce a single type of antibody
• Used in research, clinical testing, and cancer
treatment
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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)
Copyright © 2010 Pearson Education, Inc.
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)
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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)
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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)
Copyright © 2010 Pearson Education, Inc.
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.
Copyright © 2010 Pearson Education, Inc.
Figure 21.17a
Cytoplasm of any tissue cell
1 Endogenous
antigen is degraded
by protease.
Endogenous antigen—
self-protein or foreign
(viral or cancer) protein
Plasma membrane of a tissue cell
Extracellular fluid
(a) Endogenous antigens are processed and displayed on class I MHC of all cells.
Copyright © 2010 Pearson Education, Inc.
Figure 21.17a, step 1
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)
Transport
protein
(ATPase)
Plasma membrane of a tissue cell
Extracellular fluid
(a) Endogenous antigens are processed and displayed on class I MHC of all cells.
Copyright © 2010 Pearson Education, Inc.
Figure 21.17a, step 2
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.
Transport
protein
(ATPase)
Plasma membrane of a tissue cell
Extracellular fluid
(a) Endogenous antigens are processed and displayed on class I MHC of all cells.
Copyright © 2010 Pearson Education, Inc.
Figure 21.17a, step 3
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.
Copyright © 2010 Pearson Education, Inc.
Figure 21.17a, step 4
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
Copyright © 2010 Pearson Education, Inc.
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).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b
1a
Invariant chain
prevents class II
MHC from binding
to peptides in the ER.
Class II MHC is
synthesized in ER.
Cytoplasm of APC
Cisternae of
endoplasmic
reticulum (ER)
Plasma membrane of APC
Extracellular fluid
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 1a
1a
Invariant chain
prevents class II
MHC from binding
to peptides in the ER.
Class II MHC is
synthesized in ER.
Cytoplasm of APC
Cisternae of
endoplasmic
reticulum (ER)
1b Extracellular
antigen (bacterium)
is phagocytized.
Extracellular
antigen
Extracellular fluid
Plasma membrane of APC
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 1b
1a
Invariant chain
prevents class II
MHC from binding
to peptides in the ER.
Class II MHC is
synthesized in ER.
Cytoplasm of APC
2a
Cisternae of
endoplasmic
reticulum (ER)
1b Extracellular
antigen (bacterium)
is phagocytized.
Extracellular
antigen
Extracellular fluid
Class II MHC
is exported
from ER in a
vesicle.
Plasma membrane of APC
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 2a
Cytoplasm of APC
1a
Class II MHC is
synthesized in ER.
Invariant chain
prevents class II
MHC from binding
to peptides in the ER.
2a
Cisternae of
endoplasmic
Phagosome
reticulum (ER)
1b Extracellular
antigen (bacterium)
is phagocytized.
Class II MHC
is exported
from ER in a
vesicle.
2b
Phagosome merges
with lysosome, forming
a phagolysosome;
antigen is degraded.
Extracellular
antigen
Extracellular fluid
Lysosome
Plasma membrane of APC
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 2b
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.
2b
Phagosome merges
with lysosome, forming
a phagolysosome;
antigen is degraded.
Extracellular
antigen
Extracellular fluid
Lysosome
Plasma membrane of APC
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 3
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
2b
Phagosome merges
with lysosome, forming
a phagolysosome;
antigen is degraded.
Extracellular
antigen
Extracellular fluid
Lysosome
Plasma membrane of APC
Vesicle with
loaded MHC
migrates to the
plasma
membrane.
Antigenic peptide
(b) Exogenous antigens are processed and displayed on class II MHC of
antigen-presenting cells (APCs).
Copyright © 2010 Pearson Education, Inc.
Figure 21.17b, step 4
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
Activated
helper
T cells
Figure 21.18
T Cell Activation: Co-Stimulation
• Requires T cell binding to other surface receptors on
an APC
• Dendritic cells and macrophages produce surface B7
proteins when innate defenses are mobilized
• B7 binding with a CD28 receptor on a T cell is a crucial
co-stimulatory signal
• Cytokines (interleukin 1 and 2 from APCs or T cells)
trigger proliferation and differentiation of activated T
cell
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
T Cell Activation: Co-Stimulation
• Primary T cell response peaks within a week
• T cell apoptosis occurs between days 7 and
30
• Effector activity wanes as the amount of
antigen declines
• Benefit of apoptosis: activated T cells are a
hazard
• Memory T cells remain and mediate
secondary responses
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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
Copyright © 2010 Pearson Education, Inc.
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)
Copyright © 2010 Pearson Education, Inc.
Figure 21.19a
Helper T Cells
• Cause dendritic cells to express costimulatory molecules required for CD8 cell
activation
Copyright © 2010 Pearson Education, Inc.
TH cell help in cell-mediated immunity
CD4 protein
Helper T cell
1 Previously
activated TH cell
binds dendritic cell.
Class II MHC
protein
APC (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)
Copyright © 2010 Pearson Education, Inc.
CD8
protein
CD8 T cell
now activate CD8 cell
with the help of
interleukin 2 secreted
by TH cell.
Figure 21.19b
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
Copyright © 2010 Pearson Education, Inc.
Roles of Cytotoxic T(TC) Cells
• Targets
• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells (transfusions or transplants)
Copyright © 2010 Pearson Education, Inc.
Cytotoxic T Cells
• Bind to a self-nonself complex
• Can destroy all infected or abnormal cells
Copyright © 2010 Pearson Education, Inc.
Cytotoxic T Cells
• Lethal hit
• Tc cell releases perforins and granzymes by
exocytosis
• Perforins create pores through which
granzymes enter the target cell
• Granzymes stimulate apoptosis
• In some cases, TC cell binds with a Fas
receptor on the target cell, and stimulates
apoptosis
Copyright © 2010 Pearson Education, Inc.
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
TC cell
membrane
Target
cell
membrane
Target
cell
2 TC releases perforin and
Perforin
pore
Granzymes
5 The TC detaches and
3 Perforin molecules
insert into the target
cell membrane,
polymerize, and form
transmembrane pores
(cylindrical holes)
similar to those
produced by
complement
activation.
4 Granzymes enter the
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.
Copyright © 2010 Pearson Education, Inc.
Figure 21.20a
Natural Killer Cells
• Recognize other signs of abnormality
• Lack of class I MHC
• Antibody coating a target cell
• Different surface marker on stressed cells
• Use the same key mechanisms as Tc cells for
killing their target cells
Copyright © 2010 Pearson Education, Inc.
Regulatory T (TReg) Cells
• Dampen the immune response by direct
contact or by inhibitory cytokines
• Important in preventing autoimmune reactions
Copyright © 2010 Pearson Education, Inc.
Cell-mediated
immunity
Antigen (Ag) intruder
Humoral
immunity
Inhibits
Inhibits
Triggers
Adaptive defenses
Innate defenses
Surface Internal
barriers defenses
Ag-infected
body cell engulfed
by dendritic cell
Becomes
Ag-presenting cell
(APC) presents
self-Ag complex
Activates
Free Ags
may directly
activate B cell
Antigenactivated
B cells
Clone and
give rise to
Activates
Naïve
Naïve
CD8
CD4
T cells
T cells
Activated to clone
Activated to clone
and give rise to Induce and give rise to
co-stimulation
Memory
cytotoxic T cells
Activated
cytotoxic
T cells
Memory
helper T cells
Activated
helper
T cells
Memory
B cells
Plasma cells
(effector B cells)
Secrete
Cytokines stimulate
Together the nonspecific killers
and cytotoxic T cells mount a
physical attack on the Ag
Copyright © 2010 Pearson Education, Inc.
Nonspecific killers
(macrophages and
NK cells of innate
immunity)
Antibodies (Igs)
Circulating lgs along with
complement mount a chemical
attack on the Ag
Figure 21.21
Organ Transplants
• Four varieties
• Autografts: from one body site to another in
the same person
• Isografts: between identical twins
• Allografts: between individuals who are not
identical twins
• Xenografts: from another animal species
Copyright © 2010 Pearson Education, Inc.
Prevention of Rejection
• Depends on the similarity of the tissues
• Patient is treated with immunosuppressive
therapy
• Corticosteroid drugs to suppress inflammation
• Antiproliferative drugs
• Immunosuppressant drugs
• Many of these have severe side effects
Copyright © 2010 Pearson Education, Inc.
Immunodeficiencies
• Congenital and acquired conditions that cause
immune cells, phagocytes, or complement to
behave abnormally
Copyright © 2010 Pearson Education, Inc.
Severe Combined Immunodeficiency (SCID)
Syndrome
• Genetic defect
• Marked deficit in B and T cells
• Abnormalities in interleukin receptors
• Defective adenosine deaminase (ADA)
enzyme
• Metabolites lethal to T cells accumulate
• SCID is fatal if untreated; treatment is with
bone marrow transplants
Copyright © 2010 Pearson Education, Inc.
Hodgkin’s Disease
• An acquired immunodeficiency
• Cancer of the B cells
• Leads to immunodeficiency by depressing
lymph node cells
Copyright © 2010 Pearson Education, Inc.
Acquired Immune Deficiency Syndrome
(AIDS)
• Cripples the immune system by interfering
with the activity of helper T cells
• Characterized by severe weight loss, night
sweats, and swollen lymph nodes
• Opportunistic infections occur, including
pneumocystis pneumonia and Kaposi’s
sarcoma
Copyright © 2010 Pearson Education, Inc.
Acquired Immune Deficiency Syndrome
(AIDS)
• Caused by human immunodeficiency virus (HIV)
transmitted via body fluids—blood, semen, and
vaginal secretions
• HIV enters the body via
• Blood transfusions
• Blood-contaminated needles
• Sexual intercourse and oral sex
• HIV
• Destroys TH cells
• Depresses cell-mediated immunity
Copyright © 2010 Pearson Education, Inc.
Acquired Immune Deficiency Syndrome
(AIDS)
• HIV multiplies in lymph nodes throughout the
asymptomatic period
• Symptoms appear in a few months to 10 years
• HIV-coated glycoprotein complex attaches to the
CD4 receptor
• HIV enters the cell and uses reverse transcriptase to
produce DNA from viral RNA
• The DNA copy (a provirus) directs the host cell to
make viral RNA and proteins, enabling the virus to
reproduce
Copyright © 2010 Pearson Education, Inc.
Acquired Immune Deficiency Syndrome
(AIDS)
• HIV reverse transcriptase produces frequent
transcription errors; high mutation rate and
resistance to drugs
• Treatment with antiviral drugs
• Reverse transcriptase inhibitors (AZT)
• Protease inhibitors (saquinavir and ritonavir)
• New Fusion inhibitors that block HIV’s entry to
helper T cells
Copyright © 2010 Pearson Education, Inc.
Autoimmune Diseases
• Immune system loses the ability to distinguish
self from foreign
• Production of autoantibodies and sensitized
TC cells that destroy body tissues
• Examples include multiple sclerosis,
myasthenia gravis, Graves’ disease, type I
diabetes mellitus, systemic lupus
erythematosus (SLE), glomerulonephritis, and
rheumatoid arthritis
Copyright © 2010 Pearson Education, Inc.
Mechanisms of Autoimmune Diseases
1. Foreign antigens may resemble self-antigens
•
Antibodies against the foreign antigen may crossreact with self-antigen
2. New self-antigens may appear, generated by
•
Gene mutations
•
Changes in self-antigens by hapten attachment or as
a result of infectious damage
Copyright © 2010 Pearson Education, Inc.
Mechanisms of Autoimmune Diseases
3. Release of novel self-antigens by trauma of
a barrier (e.g., the blood-brain barrier)
Copyright © 2010 Pearson Education, Inc.
Hypersensitivities
• Immune responses to a perceived (otherwise
harmless) threat
• Causes tissue damage
• Different types are distinguished by
• Their time course
• Whether antibodies or T cells are involved
• Antibodies cause immediate and subacute
hypersensitivities
• T cells cause delayed hypersensitivity
Copyright © 2010 Pearson Education, Inc.
Immediate Hypersensitivity
• Acute (type I) hypersensitivities (allergies)
begin in seconds after contact with allergen
• Initial contact is asymptomatic but sensitizes
the person
• Reaction may be local or systemic
Copyright © 2010 Pearson Education, Inc.
Immediate Hypersensitivity
• The mechanism involves IL-4 secreted by T
cells
• IL-4 stimulates B cells to produce IgE
• IgE binds to mast cells and basophils,
resulting in a flood of histamine release and
inducing the inflammatory response
Copyright © 2010 Pearson Education, Inc.
Anaphylactic Shock
• Systemic response to allergen that directly enters the
blood
• Basophils and mast cells are enlisted throughout the
body
• Systemic histamine releases may cause
• Constriction of bronchioles
• Sudden vasodilation and fluid loss from the
bloodstream
• Hypotensive shock and death
• Treatment: epinephrine
Copyright © 2010 Pearson Education, Inc.
Subacute Hypersensitivities
• Caused by IgM and IgG transferred via blood plasma
or serum
• Slow onset (1–3 hours) and long duration (10–15
hours)
• Cytotoxic (type II) reactions
• Antibodies bind to antigens on specific body cells,
stimulating phagocytosis and complement-mediated
lysis of the cellular antigens
• Example: mismatched blood transfusion reaction
Copyright © 2010 Pearson Education, Inc.
Subacute Hypersensitivities
• Immune complex (type III) hypersensitivity
• Antigens are widely distributed through the
body or blood
• Insoluble antigen-antibody complexes form
• Complexes cannot be cleared from a particular
area of the body
• Intense inflammation, local cell lysis, and
death may result
• Example: systemic lupus erythematosus (SLE)
Copyright © 2010 Pearson Education, Inc.
Delayed Hypersensitivities (Type IV)
• Slow onset (one to three days)
• Mechanism depends on helper T cells
• Cytokine-activated macrophages and
cytotoxic T cells cause damage
• Example: allergic contact dermatitis (e.g.,
poison ivy)
Copyright © 2010 Pearson Education, Inc.
Developmental Aspects
• Immune system stem cells develop in the liver
and spleen by the ninth week
• Bone marrow becomes the primary source of
stem cells
• Lymphocyte development continues in the
bone marrow and thymus
Copyright © 2010 Pearson Education, Inc.
Developmental Aspects
• TH2 lymphocytes predominate in the newborn,
and the TH1 system is educated as the person
encounters antigens
• The immune system is impaired by stress and
depression
• With age, the immune system begins to wane,
and incidence of cancer increases
Copyright © 2010 Pearson Education, Inc.