Essentials of Pathophysiology
CHAPTER 16
DISORDERS OF THE IMMUNE
RESPONSE
PRE LECTURE QUIZ (TRUE/FALSE)
F

T

T

F

F

Allergic rhinitis is a systemic, life-threatening
hypersensitivity reaction characterized by widespread
vasodilation that leads to severe hypotension, airway
constriction that causes difficulty breathing, and vascular
permeability that causes swelling and obstruction of the
upper airway.
Virtually any food can produce an allergic reaction.
In host-versus-graft disease, the immune cells of the
transplant recipient attack the donor cells of the
transplanted organ
Severe combined immunodeficiency is a disorder that
results from the loss of B-cell function, while all other
immune function remains normal.
The HIV-infected person can transmit the virus only when
symptoms are present and the antibody test is positive.
PRE LECTURE QUIZ
Autoimmune

Type __________ hypersensitivity responses result from
immune responses to exogenous and endogenous
antigens that produce inflammation and cause tissue
damage.

The _______________ test, a test in which purified
protein derivative is injected under the skin, is an
example of delayed-type hypersensitivity.

Rheumatoid arthritis, insulin-dependent diabetes
mellitus, ulcerative colitis, and myasthenia gravis are all
examples of probable ___________________ disease.

The HIV-infected person is at risk for many ___________
infections, potentially affecting the respiratory tract, the
gastrointestinal tract, and the nervous system.

_____________ tolerance refers to the inability to mount
an immune response against a person’s own antigens.
I
Opportunistic
Self
tuberculin
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?

TYPE I HYPERSENSITIVITY

Commonly called “allergic reactions”

Systemic or anaphylactic reactions

Local or atopic reactions (genetic)
 Rhinitis
 Food
(hay fever)
allergies
 Bronchial
asthma
 Hives
 Atopic
dermatitis (inherited)
MECHANISM OF
TYPE I
HYPERSENSITIVITY
Mast cell
Allergen
Allergen
attaches
to IgE
IgE attaches
to mast cell
Sensitized
Mast cell
Mast cell
degranulates
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
 What
the allergen binds to IgE?
inflammatory mediators are
involved? How?
QUESTION
True or False.
When mast cells degranulate, histamine is
released.
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.
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?
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?
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
MECHANISM OF TYPE II HYPERSENSITIVITY
Example incompatable
blood transfusion
Immunoglobulins
Antigens
introduced
Immunoglobulins
attach to
antigens
Complement
activated
Directly
causes
cell lysis
Cell WBCs attracted
lysis to eat cell
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?
RHOGAM
a solution of IgG anti-Rh+ antibodies
 bind to, and lead to the destruction of, Rh+
red blood cells that have passed from the fetal
circulation to the maternal circulation.
 prevents sensitization in a Rh negative mother
to Rh+ antigens,
 Sensitization can cause hemolytic disease in
the current or in subsequent pregnancies.

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.
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 antigenantibody response.
TYPE III HYPERSENSITIVITY

Free-floating antigen + antibody 
circulating immune complex in the circulatory system
 Autoimmune vasculitis
 Glomerulonephritis
 Serum sickness
 Arthus reaction
MECHANISM OF TYPE III HYPERSENSITIVITY
• Immune complexes
deposit on walls of blood
vessels and activate
complement
Immunoglobulins
Antigens
• Blood vessels are
damaged
Immune complexes
QUESTION
True or False.
Administration of certain antibiotics may result in
type III hypersensitivity reaction.
ANSWER
True
Rationale: A side effect associated with antibiotic
administration (especially penicillin) is serum
sickness, which may cause a type III
hypersensitivity reaction.
TYPE IV HYPERSENSITIVITY (CELLULAR IMMUNITY)



Cell-mediated: sensitized T cells attack antigen
Direct cell-mediated cytotoxicity
 Viral reactions
Delayed-type hypersensitivity
 Tuberculin test
 Allergic contact dermatitis
 Hypersensitivity pneumonitis
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
MECHANISMS OF TYPE IV HYPERSENSITIVITY
An antigen enters the system
The antigen is taken up,
processed, and presented on
the surface of APC and local
cells
APC cells present epitope to T4
helper cells
T4 cells stimulate T8 cytotoxic
cells to destroy local cells that
have taken up the antigen.
T4 cells release cytokines that
initiated an inflamatory response
Example: TB tine test
T4
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
Antitissue antibodies appear in blood (e.g., antithyroid
antibodies)
TRANSPLANT REJECTION

Host-versus-graft disease (HVGD)

Hyperacute


Acute


Circulating antibodies react with graft
Exposure to transplant causes activation of immune
system, especially T cells
Chronic

Blood vessels in transplant gradually damaged
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 will cause GVHD
Discussion:
 Why might this be the case?

QUESTION
True or False.
Patients who suffer from autoimmune disease
have hypoactive immune systems.
ANSWER
False
Rationale: In autoimmune diseases, the immune
system is hyperactive—it attacks self-antigens
and destroys its own body tissues.
IMMUNODEFICIENCY


Primary
 B-cell deficiencies
 Ig deficiencies
 T-cell deficiencies
 Combined immunodeficiencies
Acquired
 AIDS
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
HIV INFECTS A CELL
Bind
Binds to CD4 protein
receptor
Uncoat
Integrate
• Which of your body
cells have CD4
proteins and CD4
receptors?
• What does reverse
transcriptase do?
THE INFECTED CELL PRODUCES NEW HIV
Polyprotein
broken into
subunits by
protease
Protein subunits are
assembled into new
virus particles
Transcription
Exit
HIV may lie dormant in
the genome for many
years before it is
activated to produce
viral proteins
Viral proteins are
produced in a long
string called a
polyprotein
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
ANSWER
1
Rationale: In the illustration, step #1 marks the
point of ATTACHMENT between HIV and the
CD4 receptor site on the T lymphocyte.
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
AIDS-ASSOCIATED ILLNESSES




Opportunistic infections
 Respiratory
 Gastrointestinal
 Nervous system
AIDS dementia complex
Malignancies
Wasting syndrome
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?