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Chapter 19
Disorders
Associated
with the Immune
System
© 2013 Pearson Education, Inc.
Lectures prepared by Christine L. Case
Insert Fig CO 19
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Hypersensitivity Reactions
 Response to antigens (allergens) leading to
damage
 Types of reactions
 Anaphylactic
 Cytotoxic
 Immune complex
 Delayed cell-mediated
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Types of Hypersensitivity
Type of Reaction
Type I (anaphylactic)
Type II (cytotoxic)
Type III (immune complex)
Type IV (delayed cellmediated)
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Time After Exposure for
Clinical Symptoms
<30 min
5–12 hours
3–8 hours
≥1 day
Type I (Anaphylactic) Reactions
 IgE attached to mast cells and basophils
 Antigen binds to two adjacent IgE
 Mast cells and basophils undergo degranulation,
which releases mediators:
 Histamine
 Leukotrienes
 Prostaglandins
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Figure 19.1a The mechanism of anaphylaxis.
Mast cell or
basophil
Granule
IgE
Antigen
Histamine and
other mediators
IgE antibodies, produced in response to an antigen,
coat mast cells and basophils. When an antigen bridges
the gap between two adjacent antibody molecules of the
same specificity, the cell undergoes degranulation and
releases histamine and other mediators.
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Figure 19.1b The mechanism of anaphylaxis.
Mast cells
A degranulated mast cell that has reacted
with an antigen and released granules of
histamine and other reactive mediators
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Type I (Anaphylactic) Reactions
 Systemic anaphylaxis
 May result in circulatory collapse and death
 Localized anaphylaxis
 Hives, hay fever, and asthma
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Figure 19.2 Localized anaphylaxis.
A micrograph of pollen grains
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A micrograph of a house mite on
fabric
Figure 19.3 A skin test to identify allergens.
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Preventing Anaphylactic Reactions
 Desensitizing injections of antigen
 Cause production of IgG, so that IgG antibodies will
act as blocking antibodies
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Type II (Cytotoxic) Reactions
 Involve IgG or IgM antibodies and complement
 Complement activation causes cell lysis or
damage by macrophages
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Table 19.2 The ABO Blood Group System
Insert Table 19.2
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Figure 19.4 Hemolytic disease of the newborn.
Placenta
Rh+ father.
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Rh– mother carrying
her first Rh+ fetus.
Rh antigens from
the developing fetus
can enter the
mother's blood
during delivery.
In response to the
fetal Rh antigens,
the mother will
produce anti-Rh
antibodies.
If the woman becomes
pregnant with another
Rh+ fetus, her anti-Rh
antibodies will cross
the placenta and
damage fetal red blood
cells.
Figure 19.5 Drug-induced thrombocytopenic purpura.
Platelet
Drug (hapten)
Drug binds to platelet,
forming hapten–platelet
complex.
Complex induces formation
of antibodies against
hapten.
Hapten–platelet
complex
Anti-hapten
antibody
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Complement
Action of antibodies
and complement causes
platelet destruction.
Type III (Immune Complex) Reactions
 IgG antibodies and antigens form immune
complexes that lodge in basement membranes
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Figure 19.6 Immune complex–mediated hypersensitivity.
Basement
membrane of
blood vessel
Ag
Endothelial
cell
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Immune complexes
are deposited in wall
of blood vessel.
Presence of immune
complexes activates
complement and
attracts inflammatory
cells such as
neutrophils.
Neutrophils
Enzymes released
from neutrophils
cause damage to
endothelial cells
of basement
membrane.
Type IV (Cell-Mediated) Reactions
 Delayed-type hypersensitivities due to
T cells
 Cytokines attract macrophages and TC cells
 Initiate tissue damage
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Figure 19.7 The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy
plant.
Pentadecacatechol
molecules
Skin
protein
Dermatitis on arm
Pentadecacatechol
molecules combined
with skin proteins
Poison ivy
7–10 days
1–2 days
T cells:
T memory
Sensitization
cells: Immune
step
response
(No dermatitis)
PRIMARY CONTACT
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Many active
T cells: Disease
Dermatitis
SECONDARY CONTACT
Figure 19.8 Allergic contact dermatitis.
Insert Fig 19.8
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What Is the Delayed Rash?
Clinical Focus: A Delayed Rash, unnumbered figure, page 537.
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What Is the Delayed Rash?
 A patient developed a rash 7 days after taking
penicillin.
 Was this the patient’s first exposure to penicillin?
 What is the delayed reaction?
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Autoimmune Diseases
 Clonal deletion during fetal development ensures
self-tolerance
 Autoimmunity is loss of self-tolerance
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Autoimmune Diseases
 Cytotoxic: antibodies react with cell-surface
antigens
 Graves’ disease
 Immune complex: immune complexes of IgM, IgG,
and complement deposit in tissues
 Systemic lupus erythematosus
 Cell-mediated: mediated by T cells
 Psoriasis
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HLA Reactions
 Histocompatibility antigens: self antigens on cell
surfaces
 Major histocompatibility complex (MHC): genes
encoding histocompatibility antigens
 Human leukocyte antigen (HLA) complex: MHC
genes in humans
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Figure 19.9 Tissue typing, a serological method.
Lymphocyte
being tested
Anti-HLA antibodies
attach to HLAs on
lymphocyte.
HLA
Complement
and trypan
blue dye are
added.
Cell damaged
by complement
takes up dye.
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Diseases Related to Specific HLAs
Disease
Increased Risk of Occurrence
with Specific HLA
Multiple sclerosis
5 times
Rheumatic fever
4–5 times
Addison’s disease
4–10 times
Graves’ disease
10–12 times
Hodgkin’s disease
1.4–1.8 times
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Reactions to Transplantation
 Transplants may be attacked by T cells,
macrophages, and complement-fixing antibodies
 Transplants to privileged sites do not cause an
immune response
 Stem cells may allow therapeutic cloning to avoid
rejection
 Embryonic stem cells are pluripotent
 Adult stem cells have differentiated to form specific cells
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Figure 19.10 Derivation of embryonic stem cells.
(1 day) Embryo, usually a fertilized egg discarded from attempt at
in vitro fertilization.
Embryoblast (inner cell
mass of embryonic cells)
Outer cell mass
(1–5 days) Blastocyst stage; the embryo divides repeatedly and
forms a hollow ball of cells about the size of the period at the end
of a sentence.
Stem cell lines
Blood and
lymphatic cells
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Pancreatic Nerve cells
islet cells
Embryonic stem cells from embryoblast are grown on feeder cells in culture
medium. Stem cell lines and groups of stem cells form colonies in culture
medium. Different conditions, as well as growth factors added to culture medium,
direct stem cells to become stem cell lines for various tissues of the body (e.g.,
blood and lymphatic cells, pancreatic islet cells, nerve cells).
Grafts




Autograft: use of one’s own tissue
Isograft: use of identical twin’s tissue
Allograft: use of tissue from another person
Xenotransplantation product: use of nonhuman
tissue
 Hyperacute rejection: response to nonhuman Ag
 Graft-versus-host disease can result from
transplanted bone marrow that contains
immunocompetent cells
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Immunosuppression
 Prevents an immune response to transplanted
tissues
 Cyclosporine and tacrolimus suppress IL-2
 Mycophenolate mofetil inhibits T cell and B cell
reproduction
 Sirolimus blocks IL-2
 Basiliximab and daclizumab block IL-2
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The Immune System and Cancer
 Cancer cells have tumor-associated antigens
 Cancer cells are removed by immune surveillance
 CTL (activated TC) cells lyse cancer cells
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Figure 19.11 The interaction between a cytotoxic T lymphocyte (CTL) and a cancer cell.
Cancer cell
Remains of cancer cell
CTL
CTL
The small CTL has
already made a
perforation in the
cancer cell.
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The cancer cell has
disintegrated.
Immunotherapy for Cancer
 Coley’s toxin (gram-negative bacteria) stimulates
TNF
 Vaccines used against:





Marek’s disease
Feline leukemia
Human cervical cancer
Liver cancer (hepatitis B virus)
Cervical cancer (HPV vaccine)
 Monoclonal antibodies
 Herceptin
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Immunotherapy for Cancer
 Treatment of cancer using immunologic
methods
 Tumor necrosis factor, IL-2, and interferons may
kill cancer cells
 Immunotoxins link poisons with a monoclonal
antibody directed at a tumor antigen
 Vaccines contain tumor-specific antigens
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Immunodeficiencies
 Congenital: due to defective or missing genes
 Acquired: develop during an individual’s life
 Due to drugs, cancers, and infections
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Immunodeficiencies
Disease
Cells Affected
AIDS
Selective IgA immunodeficiency
TH (CD4+) cells
B, T cells
Common variable
hypogammaglobulinemia
Reticular dysgenesis
Severe combined
immunodeficiency
Thymic aplasia (DiGeorge
syndrome)
Wiskott-Aldrich syndrome
X-linked infantile (Bruton’s)
agammaglobulinemia
B, T cells (decreased
immunoglobulins)
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B, T, and stem cells
B, T, and stem cells
T cells (defective
thymus)
B, T cells
B cells (decreased
immunoglobulins)
Figure 19.12 A nude (hairless) mouse infected with Mycobacterium leprae in the hind foot.
Site of
M. leprae bacteria
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