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Chapter 15
Alterations in the
Immune Response
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Hypersensitivity
• Excessive or inappropriate activation of the immune response
• The body is damaged by the immune response, rather than by
the antigen (often called allergen)
Discussion:
• How many different allergies do the members of this class
have?
• What are their common signs and symptoms?
• Can the general process of inflammation explain these signs
and symptoms?
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Type I Hypersensitivity
• Commonly called “allergic reactions”
• Systemic or anaphylactic reactions
• Local or atopic reactions (genetic)
– Rhinitis (hay fever)
– Food allergies
– Bronchial asthma
– Hives
– Atopic dermatitis
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Mast cell
Mechanism of
Type I
Hypersensitivity
Sensitized
Mast cell
IgE attaches
to mast cell
Allergen
attaches
to IgE
Mast cell
degranulates
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Type I Allergies Are Mediated by IgE
• What cells must be involved in this process:
– On the first exposure to the allergen?
– On repeated exposure?
– When the allergen binds to IgE?
– What inflammatory mediators are involved?
How?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Tell whether the following statement is true or false.
When mast cells degranulate, histamine is released.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
True
Rationale: Histamine is one of the first chemical
mediators released during the inflammatory response as
a result of mast cell degranulation. Mast-cell stabilizers
(used to treat asthma) prevent the histamine from being
released; antihistamines (used to treat allergies)
compete with histamine for receptor sites, lessening the
inflammatory response.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Anaphylaxis
• Systemic response to the inflammatory mediators
released in type I hypersensitivity
– Histamine, acetylcholine, kinins, leukotrienes, and
prostaglandins all cause vasodilation
º What will happen when arterioles vasodilate
throughout the body?
– Acetylcholine, kinins, leukotrienes, and
prostaglandins all can cause bronchoconstriction
º What will happen when the bronchioles constrict?
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Scenario
A woman had an anaphylactic reaction and you are trying
to explain the mechanism to her husband; he says he
can see what you mean, but it does not make sense
because what his wife experienced was different.
• She said her heart was pounding and she was terrified.
• Her eyes were dilated.
• She was shaking.
Question:
• How could anaphylaxis cause these signs and symptoms?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Type II Hypersensitivity
• Cytotoxic
• IgG or IgM attack antigens on cell surfaces
– Usually involves antigens on red or
white blood cells
– Transfusion reactions
– Rh disease
– Drug reactions
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Mechanism of
Type II
Hypersensitivity
Immunoglobulins
Antigens
attached to cell
membrane
Directly
causes
cell lysis
Immunoglobulins
attach to
antigens
Complement
activated
Cell WBCs attracted
lysis to eat cell
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Scenario
A woman is Rh negative and her husband is Rh
positive.
• She is pregnant with their first child and the doctor
has prescribed RhoGAM, but the woman is confused
about this.
• She says she does not want to take any drugs while
she is pregnant—and besides, the doctor told her
that her first child was not at much risk for Rh
disease.
Question:
• Why can’t she wait to take RhoGAM until she gets
pregnant again and really needs it?
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Question
Why is type O blood considered the universal donor?
a. It has both A and B antigens on the RBC.
b. It has neither A nor B antigens on the RBC.
c. It has no antibodies in the plasma.
d. It has A and B antibodies in the plasma.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
b. It has neither A nor B antigens on the RBC.
Rationale: Antigens are the components that elicit an
immune response (type II hypersensitivity reaction).
Type O blood has no antigens on the RBC, so anyone
can receive it because there is nothing to stimulate
production of antibodies against it. The fact that type O
blood has both A and B antibodies has nothing to do
with creating the antigen-antibody response.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Type III Hypersensitivity
• Free-floating antigen + antibody 
circulating immune complex
– Autoimmune vasculitis
– Glomerulonephritis
– Serum sickness
– Arthus reaction
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Mechanism of
Type III
Hypersensitivity
Immunoglobulins
Antigens
• Immune complexes
deposit on walls of
blood vessels and
activate complement
• Blood vessels are
damaged
Immune complexes
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Question
Tell whether the following statement is true or false.
Administration of certain antibiotics may result in type III
hypersensitivity reaction.
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Answer
True
Rationale: A side effect associated with antibiotic
administration (especially penicillin) is serum sickness,
which may cause a type III hypersensitivity reaction.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Type IV Hypersensitivity
• Cell-mediated: sensitized T cells attack antigen
• Direct cell-mediated cytotoxicity
– Viral reactions
• Delayed-type hypersensitivity
– Tuberculin test
– Allergic contact dermatitis
– Hypersensitivity pneumonitis
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Mechanisms of Type IV Hypersensitivity
TH1 cell
Antigen
Sensitized
TH1 cell
Activated
Cytotoxic T
cell
Delayed-type
hypersensitivity:
TH1 cell secretes
inflammatory mediators
Direct cell-mediated cytotoxicity:
Cytotoxic T cells kill tissue cells
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Autoimmune Diseases
• Immune system attacks self-antigens
• Normally, self-reactive immune cells are killed in
the lymphoid organs or suppressed by regulatory
T cells
• In autoimmunity, this self-tolerance breaks down
• Immune system destroys body tissues
• Anti-tissue antibodies appear in blood (e.g., antithyroid antibodies)
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Transplant Rejection
• Host-versus-graft disease (HVGD)
• Hyperacute
– Circulating antibodies react with graft
• Acute
– Exposure to transplant causes activation of
immune system, especially T cells
• Chronic
– Blood vessels in transplant gradually damaged
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Graft-versus-host Disease
• Transplanted immune cells attack host
• A recent study suggested that men who get bone
marrow transplants from women might be more
prone to GVHD than men who get bone marrow
transplants from other men
• It also suggested that the more children a woman has
had, the more likely her bone marrow was to cause
GVHD
Discussion:
• Why might this be the case?
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Question
Tell whether the following statement is true or false.
Patients who suffer from autoimmune disease have
hypoactive immune systems.
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Answer
False
Rationale: In autoimmune diseases, the immune system
is hyperactive—it attacks self-antigens and destroys its
own body tissues.
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Immunodeficiency
• Primary
– B-cell deficiencies
– Ig deficiencies
– T-cell deficiencies
– Combined immunodeficiencies
• Acquired
– AIDS
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Human Immunodeficiency Virus
• Transmitted by body fluids
– Sexual contact
– Breast milk
– Blood-to-blood contact
º Contaminated needles
º Transfusions
º During pregnancy or birth
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HIV Infects a Cell
Binds to CD4
protein
receptor
• Which of your body
cells have CD4
proteins and CD4
receptors?
• What does reverse
transcriptase do?
Reverse
transcriptase
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The Infected Cell Produces New HIV
HIV may lie dormant in
the genome for many
years before it is
activated to produce
viral proteins
Polyprotein
broken into
subunits by
protease
Protein subunits are
assembled into new
virus particles
Viral proteins are
produced in a long
string called a
polyprotein
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Question
One AIDS drug is a fusion inhibitor (Fuzeon)—the drug
prevents fusion of HIV to the CD4 receptor. In the
previous slides’ illustrations, which step in the infection
process is targeted by a fusion inhibitor?
a. 1
b. 3
c. 6
d. 8
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Answer
a. 1
Rationale: In the illustration, step #1 marks the point of
attachment between HIV and the CD4 receptor site on
the T lymphocyte.
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Course of HIV Infection
• Primary infection phase
– Signs of systemic infection
– Seroconversion: immune system responds and
antibodies against HIV appear (1–6 months)
• Latent period
– Virus is replicating, TH cell count gradually falls
– May last 10–11 years or longer
• Overt AIDS
– TH cell count <200 cells/mL or AIDS-defining illness
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AIDS-associated Illnesses
• Opportunistic infections
– Respiratory
– Gastrointestinal
– Nervous system
• AIDS dementia complex
• Malignancies
• Wasting syndrome
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Scenario
A man was diagnosed as HIV-positive.
• He says this is nonsense because the test does
not measure whether he is sick or not
• In fact, it means “his immune system is
working”
Question:
• Is he right?
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