2012 Pearson Education Inc.

Lecture prepared by Mindy Miller-Kittrell

North Carolina State University
Chapter 18
AIDS and
Other Immune
Disorders
Hypersensitivities
Hypersensitivity
Any immune response against a foreign
antigen exaggerated beyond the norm
Four types
Type I (immediate)
Type II (cytotoxic)
Type III (immune complexmediated)
Type IV (delayed or cell-mediated)
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Hypersensitivities
Type I (Immediate) Hypersensitivity
Results from the release of inflammatory
molecules in response to an antigen
Localized or systemic reaction
Develops soon after exposure to an antigen
Commonly called allergy
The antigens that stimulate it are called
allergens
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Figure 18.1a The mechanisms of a type I hypersensitivity reaction: sensitization
Allergen (antigen)
Antigen-presenting cell (APC)
phagocytizes and processes
antigen.
APC presents
epitope to Th2 cell.
Th2 cell
B cell
Plasma
cell
IL-4 IL-4 from Th2
cell stimulates selected
B cell clone.
B cells become plasma cells
that secrete IgE.
IgE against allergen
IgE stem binds to
mast cells, basophils,
and eosinophils.
Eosinophil Basophil
IgE
Mast cell
Sensitization
Figure 18.1b The mechanisms of a type I hypersensitivity reaction: degranulation
Subsequent exposure
to allergen
Degranulation
Sensitized mast cell,
basophil, or eosinophil
Histamines, kinins,
proteases, leukotrienes,
prostaglandins, and other
inflammatory molecules
Hypersensitivities
Type I (Immediate) Hypersensitivity
Roles of degranulating cells in an allergic
reaction
Degranulation occurs after cells are sensitized
Mast cells
Basophils
Eosinophils
Degranulation releases histamine, kinins,
proteases, leukotrienes, and prostaglandins
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Hypersensitivities
Type I (Immediate) Hypersensitivity
Clinical signs of localized allergic reactions
Usually mild
Site of reaction depends on portal of entry
Small inhaled allergens may reach lungs and
cause asthma
Some foods contain allergens
May cause diarrhea and other gastrointestinal
signs and symptoms
Local skin inflammation may produce hives or
urticaria
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Figure 18.2 Some common allergens-overview
Figure 18.3 Urticaria
Hypersensitivities
Type I (Immediate) Hypersensitivity
Clinical signs of systemic allergic reactions
Many mast cells may degranulate at once,
releasing large amounts of histamine and
inflammatory mediators
Acute anaphylaxis or anaphylactic shock can
result
Clinical signs are those of suffocation
Must be treated promptly with epinephrine
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Hypersensitivities
Type I (Immediate) Hypersensitivity
Diagnosis of type I hypersensitivity
Diagnosis based on detection of high levels of
IgE against specific allergen
ImmunoCAP specific IgG blood test, CAP
RAST, pharmacia CAP
Alternatively, can diagnose using skin tests
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Figure 18.4 Skin tests for diagnosing type I hypersensitivity
Hypersensitivities
Type I (Immediate) Hypersensitivity
Prevention of type I hypersensitivity
Identify and avoid allergens
Identify food allergens by eliminating suspected
foods from diet
Immunotherapy can help prevent allergic
reactions
Administer a series of injections of dilute allergen
Must be repeated every two to three years
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Hypersensitivities
Type I (Immediate) Hypersensitivity
Treatment of type I hypersensitivity
Administer drugs that counteract inflammatory
mediators
Antihistamines neutralize histamine
Treat asthma with a corticosteroid and a
bronchodilator
Epinephrine neutralizes many mechanisms of
anaphylaxis
Relaxes smooth muscle
Reduces vascular permeability
Severe asthma and anaphylactic shock require
emergency treatment
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Hypersensitivities
Type II (Cytotoxic) Hypersensitivity
Results when cells are destroyed by an immune
response
Often the combined activities of complement and
antibodies
A component of many autoimmune diseases
Two significant examples
Destruction of blood cells following an
incompatible blood transfusion
Destruction of fetal red blood cells in hemolytic
disease of the newborn
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Hypersensitivities
Type II (Cytotoxic) Hypersensitivity
The ABO system and transfusion reactions
Blood group antigens are surface molecules of red
blood cells
Each persons red blood cells have A antigen, B
antigen, both antigens, or neither antigen
Transfusion reaction can result if individual receives
different blood type
Donors blood group antigens may stimulate the
production of antibodies in the recipient
Causes destruction of the transfused cells
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Hypersensitivities
Type II (Cytotoxic) Hypersensitivity
The ABO system and transfusion reactions
Recipient has preexisting antibodies to foreign
blood group antigens
Immediate destruction of donated blood cells can
occur
Recipient has no preexisting antibodies to foreign
blood group antigens
Transfused cells initially circulate and function
normally
Eventually recipients immune system destroys
foreign antigens
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Figure 18.5 Events leading to hemolysis
Type A antigens on red
blood cells of patient
Anti-B
antibody
Donated red blood cells
with B antigen
Complement
Hemoglobin
Transfusion
Hemolysis
Agglutination and
complement binding
Hypersensitivities
Type II (Cytotoxic) Hypersensitivity
The Rh system and hemolytic disease of the
newborn
Rh antigen
Common to red blood cells of humans and
rhesus monkeys
About 85% of humans are Rh positive (Rh+)
Rh woman carrying an Rh+ fetus may be at
risk for hemolytic disease
RhoGAM administered to prevent hemolytic
disease of the newborn
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Figure 18.6 Events in the development of hemolytic disease of the newborn-overview
Hypersensitivities
Type II (Cytotoxic) Hypersensitivity
Drug-induced cytotoxic reactions
Some drug molecules bind larger molecules
Stimulate the production of antibodies
Can produce various diseases
Immune thrombocytopenic purpura
Agranulocytosis
Hemolytic anemia
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Figure 18.7 Events in the development of immune thrombocytopenic purpura
Platelet
Drug
Drug-platelet
complex
Drug molecules bind to platelets,
forming drug-platelet complex.
Complexes are antigenic,
triggering a humoral
immune response.
Antibodies bind to drug
molecules; complement
binds to antibodies.
Complement
Membrane attack
complexes of complement
lyse platelet, which leaks
cytoplasm.
Hypersensitivities
Type III (Immune ComplexMediated)
Hypersensitivity
Caused by formation of immune complexes
Can cause localized reactions
Hypersensitivity pneumonitis
Glomerulonephritis
Can cause systemic reactions
Systemic lupus erythematosus
Rheumatoid arthritis
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Figure 18.8 The mechanism of type III (immune-complex mediated) hypersensitivity-overview
Antigens combine with
antibodies to form
antigen-antibody complexes.
Antigen
Antibody (IgG)
Antigen-antibody complex
Phagocytes remove most
of the complexes, but
some lodge in the walls
of blood vessels.
There the complexes
activate complement.
Inactive complement
Active complement
Antigen-antibody complexes
and activated complement
attract and activate
neutrophils, which release
inflammatory chemicals.
Neutrophil
Inflammatory chemicals
Inflammatory chemicals
damage underlying
blood vessel wall.
Hypersensitivities
Type III (Immune ComplexMediated)
Hypersensitivity
Hypersensitivity pneumonitis
Inhalation of antigens into lungs stimulates
antibody production
Subsequent inhalation of the same antigen
results in formation of immune complexes
Activates complement
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Hypersensitivities
Type III (Immune ComplexMediated)
Hypersensitivity
Glomerulonephritis
Immune complexes in the blood are deposited in
glomeruli
Damage to the glomerular cells impedes blood
filtration
Kidney failure and, ultimately, death result
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Hypersensitivities
Type III (Immune ComplexMediated)
Hypersensitivity
Rheumatoid arthritis
Immune complexes deposited in the joint
Results in release of inflammatory chemicals
The joints begin to break down and become
distorted
Trigger not well understood
Treated with anti-inflammatory drugs
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Figure 18.9 The crippling distortion of joints characteristic of rheumatoid arthritis
Autoimmune Diseases
Type III (Immune ComplexMediated)
Hypersensitivity
Systemic lupus erythematosus
Autoantibodies against DNA result in immune
complex formation
Many other autoantibodies can also occur
Against red blood cells, platelets, lymphocytes,
muscle cells
Trigger unknown
Immunosuppressive drugs reduce autoantibody
formation
Glucocorticoids reduce inflammation
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Figure 18.10 The characteristic facial rash of systemic lupus erythematosus
Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
Inflammation 12 to 24 hr after contact with
certain antigens
Is due to actions of antigen, antigen-presenting
cells, and T cells
Delay reflects the time it takes for macrophages
and T cells to migrate to and proliferate at the
site of the antigen
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Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
The tuberculin response
An injection of tuberculin beneath the skin causes
reaction in individual exposed to tuberculosis or
tuberculosis vaccine
Used to diagnose contact with antigens of
M. tuberculosis
No response when individual not infected or
vaccinated
Red, hard swelling develops in individuals
previously infected or immunized
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Figure 18.11 A positive tuberculin test
Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
Allergic contact dermatitis
Cell-mediated immune response
Results in an intensely irritating skin rash
Triggered by chemically modified skin proteins that
the body regards as foreign
Acellular, fluid-filled blisters develop in severe cases
Can be treated with glucocorticoids
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Figure 18.12 Allergic contact dermatitis
Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
Graft rejection
Rejection of tissues or organs that have been
transplanted
Grafts perceived as foreign by a recipient undergo
rejection
Immune response against foreign MHC on graft cells
Rejection depends on degree to which the graft is
foreign to the recipient
Based on the type of graft
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Figure 18.13 Types of grafts
Autograft
Isograft Allograft Xenograft
Genetically identical
sibling or clone
Genetically different
member of same species
Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
Graft-versus-host disease
Donated bone marrow cells regard patients cells as
foreign
Donor and recipient differ in MHC class I molecules
Grafted T cells attack the recipients tissues
Donor and recipient differ in MHC class II molecules
Grafted T cells attack the hosts antigen-presenting
cells
Immunosuppressive drugs can stop graft-versus-
host disease
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Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
Donor-recipient matching and tissue typing
MHC compatibility between donor and recipient
difficult because of a high degree of variability
The more closely the donor and recipient are related,
the smaller the difference in their MHC
Preferable that grafts are donated by a parent or
sibling
Tissue typing used to match donor and recipient
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Hypersensitivities
Type IV (Delayed or Cell-Mediated)
Hypersensitivity
The actions of immunosuppressive drugs
Immunosuppressive drugs important to
transplantation success
Classes of immunosuppressive drugs
Glucocorticoids
Cytotoxic drugs
Cyclosporine
Lymphocyte-depleting therapies
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Autoimmune Diseases
Occur more often in the elderly
Are more common in women than in men
May result when an individual begins to
make autoantibodies or cytotoxic T cells
against normal body components
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Autoimmune Diseases
Causes of Autoimmune Diseases
Estrogen may stimulate destruction of tissue by
cytotoxic T cells
Some maternal cells may cross the placenta and
trigger autoimmune disease later in life
Environmental factors include viral infections
Genetic factors include certain MHC genes
T cells may encounter self-antigens that are
normally hidden
Microorganisms may trigger autoimmunity because
of molecular mimicry
Failure of the normal control mechanisms of the
immune system
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Autoimmune Diseases
Examples of Autoimmune Diseases
Two major categories
Systemic autoimmune diseases
Single-organ autoimmune diseases
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Autoimmune Diseases
Examples of Autoimmune Diseases
Single-organ autoimmune diseases
Autoimmunity affecting blood cells
Autoimmune hemolytic anemia
Autoimmunity affecting endocrine organs
Type I diabetes mellitus
Graves disease
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Autoimmune Diseases
Examples of Autoimmune Diseases
Single-organ autoimmune diseases
Autoimmunity affecting nervous tissue
Multiple sclerosis
Autoimmunity affecting connective tissue
Rheumatoid arthritis
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Immunodeficiency Diseases
Conditions resulting from defective immune
mechanisms
Two general types
Primary
Result from some genetic or developmental defect
Develop in infants and young children
Acquired
Develop as direct consequence of some other
recognized cause
Develop in later life
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Immunodeficiency Diseases
Primary Immunodeficiency Diseases
Many inherited defects in all the bodys lines
of defenses
Chronic granulomatous disease
Severe combined immunodeficiency disease
(SCID)
DiGeorge syndrome
Bruton-type agammaglobulinemia
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Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Result from a number of causes
Severe stress
Excess production of corticosteroids suppresses
cell-mediated immunity
Malnutrition and environmental factors
Inhibit production of B cells and T cells
Acquired immunodeficiency syndrome (AIDS)
Opportunistic infections, low CD4 cells, presence
of HIV
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Figure 18.14 Diseases associated with AIDS-overview
Table 18.6 Opportunistic Infections Associated with AIDS
Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
AIDS pathogenesis and its virulence factors
Human immunodeficiency virus (HIV)
Retrovirus
Two major types
HIV-1 is prevalent in the United States and Europe
HIV-2 is prevalent in West Africa
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Figure 18.15 Artists conception of HIV
Reverse
transcriptase
Capsid
Integrase
Envelope
Protease
tRNA
gp41
gp120
ssRNA
genome
Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
AIDS pathogenesis and its virulence factors
Origin of HIV
Likely arose from mutation of the simian
immunodeficiency virus (SIV)
Estimated to have emerged in the human
population around 1930
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Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Replication of HIV
Attachment
Entry and uncoating
Synthesis of DNA
Integration
Synthesis of RNA and polypeptides
Release
Assembly and maturation
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Figure 18.16 The replication cycle of HIV-overview
Figure 18.17 The process by which HIV attaches to and enters a host cell-overview
Figure 18.18 Action of reverse transcriptase-overview
Figure 18.19 The course of AIDS
HIV in blood
CD4 (helper) T cell count
Antibody against HIV
Weeks Years
H
I
V

R
N
A

c
o
p
i
e
s
/
m
l

p
l
a
s
m
a

C
D
4

T

c
e
l
l
s
/
m
m
3

b
l
o
o
d

Primary infection
Clinical latency
Opportunistic
diseases
Death
Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Epidemiology of AIDS
First recognized in young male homosexuals in
the U.S.
Now found worldwide
HIV in blood, semen, saliva, vaginal secretions,
and breast milk concentrated enough to cause
infection
Must be injected into the body or contact a tear or
lesion in the skin or mucous membranes
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Figure 18.20 The global distribution of HIV/AIDS
North America
1.4 million
Caribbean
240,000
Latin America
2 million
Western
and Central
Europe
850,000
North Africa
& Middle East
310,000
Sub-Saharan
Africa
24.4 milion
Eastern Europe
& Central Asia
1.5 million
East Asia & Pacific
850,000
South &
Southeast Asia
3.8 million
Australia &
New Zealand
59,000
Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Epidemiology of AIDS
HIV is transmitted primarily via sexual contact and
intravenous drug use
HIV is also transmitted across the placenta and in
breast milk
Certain behaviors increase the risk of infection
Anal intercourse
Sexual promiscuity
Intravenous drug use
Sexual intercourse with anyone engaging in the
previous three behaviors
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Figure 18.21 Modes of HIV transmission in males over 12 years of age in the U.S. during 2007
Male homosexual contact
plus use of injected
drugs
Heterosexual
contact
Use of injected
drugs
Male homosexual
contact
Other 0.5%
32%
3%
12%
53%
Adult Males
Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Diagnosis, treatment, and prevention
Diagnosis involves detecting antibodies against HIV
Can indicate infection with HIV but not presence
of AIDS
Small percentage of infected individuals are
long-term nonprogressors
Appear not to develop AIDS
Possibly because of defective virions, mutated
coreceptors for the virus, or well-developed immune
systems
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Immunodeficiency Diseases
Acquired Immunodeficiency Diseases
Diagnosis, treatment, and prevention
Antiretroviral therapy (ART)
A cocktail of several antiviral drugs
Reduces viral replication, but infection remains
Vaccine development has been problematic
Diseases associated with AIDS are treated
individually
Individuals can slow the AIDS epidemic with
numerous personal decisions
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