Chapter
19:
Disorders
of
the
Immune
Response
 1




I.
 Alterations
of
the
Immune
System

A. Immunodeficiency
states

B. Allergic
or
hypersensitivity
reactions

C. Transplantation
rejection

D. Autoimmune
disorders

II.
 Immunodeficiency
Disorders

A. Abnormality
in
the
immune
system
that
renders
a
person
susceptible
to

diseases
normally
prevented
by
an
intact
immune
system

B. Classifications

1. Primary

congenital
or
inherited

2. Secondary

acquired
later
in
life

a. Malnutrition

b. Infection

HIV,
AIDS

c. Disseminated
cancers

neoplastic
diseases

lymphoma

d. Immunosuppressive
therapy

corticosteroids
or
transplant

rejection
medications

C. Warning
Signs
of
Immunodeficiency
by
Jeffrey
Modell
Foundation/Immune

Deficiency
Foundation

1. Eight
or
more
new
ear
infections
within
1
year

2. Two
or
more
serious
sinus
infections
within
1
year

3. Two
or
more
months
on
antibiotics
with
little
effect

4. Two
or
more
pneumonias
within
1
year

5. Failure
of
an
infant
to
gain
weight
or
grow
normally

6. Recurrent,
deep
skin
or
organ
abscesses

7. Persistent
thrush
in
mouth
or
elsewhere
on
skin,
after
1
year
of
age

8. Need
for
intravenous
antibiotics
to
clear
infections

9. Two
or
more
deep‐seated
infections

10. A
family
history
of
primary
immunodeficiency

III.
 Four
Major
Categories
of
Immune
Mechanisms

A. Humoral
or
antibody‐mediated
immunity

B
lymphocytes

B. Cell‐mediated
immunity

T
lymphocytes

C. Complement
system

D. Phagocytosis

neutrophils
and
macrophages

IV.
 Humoral
Immunodeficiencies

A. Humoral
immunodeficiencies
involve
B‐cell
function
and
immunoglobulin

production

B. Increase
the
risk
of
recurrent
pyogenic
infections

C. Humoral
immunity
usually
is
not
as
important
in
defending
against

intracellular
bacteria
(mycobacteria),
fungi,
and
protozoa

D. Viruses
usually
are
handled
normally,
except
for
the
enteroviruses
that
cause

gastrointestinal
infections

V.
 Primary
Humoral
Immunodeficiency
Disorders

A. Genetic
disorder
of
B
lymphocytes

B. Approximately
70%
of
primary
immunodeficiencies



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 2



C. Maturation
cycle
initially
involves
the
production
of
surface
IgM,
migration

from
the
bone
marrow
to
the
peripheral
lymphoid
tissue,
and
switching
to

the
production
of
specialized
IgM‐,
IgA‐,
IgD‐,
IgE‐,
or
IgG‐secreting
plasma

cells
after
antigenic
stimulation

D. Immunoglobulin
production
depends
on

1. Differentiation
of
stem
cells
into
mature
B
lymphocytes

2. Antigen‐dependent
generation
of
immunoglobulin‐producing
plasma

cells

E. Can
interrupt
the
production
of
one
or
all
of
the
immunoglobulins

VI.
 Combine
T‐Cell
and
B‐Cell
Immunodeficiencies

A. Affect
all
aspects
of
immune
function

B. Severe
combined
immunodeficiency
represents
a
life‐threatening
absence
of

immune
function

1. Absence
of
all
T‐
and
B‐cell
function
and,
in
some
cases,
a
lack
of
NK
cells

2. Affected
infants
have
a
disease
course
that
resembles
AIDS,
with
failure
to

thrive,
chronic
diarrhea,
and
opportunistic
infections

3. X‐linked
SCID

a. Boys
>
girls

b. Caused
by
a
genetic
defect
in
the
common
gamma‐chain
subunit
(γc)

of
cytokine
receptors

C. Combined
immunodeficiency
(CID)
is
distinguished
from
SCID
by
the

presence
of
low,
but
not
absent,
T‐cell
function

1. Although
antibody‐forming
capacity
is
impaired
in
most
cases,
it
is
not

absent

2. Autosomal
pattern
of
inheritance
is
common


a. Ataxia‐telangiectasia

i. Complex
syndrome
of
neurologic,
immunologic,
endocrinologic,

hepatic,
and
cutaneous
abnormalities

ii. Autosomal
recessive
disorder

iii. Characterizations

o Cerebellar
ataxia

poor
muscle
coordination

o Appearance
of
telangiectases

lesions
consisting
of
dilated

capillaries
and
arterioles
on
the
skin
and
conjunctival
surfaces

of
the
eye

b. Wiskott‐Aldrich
syndrome

i. X‐linked
recessive
disorder
that
becomes
symptomatic
during
the

first
year
of
life

ii. Plagued
by
eczema,
low
platelet
counts,
and
susceptibility
to

bacterial
infections

iii. Bleeding
episodes
or
symptoms
due
to
infection
usually
begin

within
the
first
6
months
of
life

iv. Prone
to
septicemia
and
meningitis,
lethal
varicella

v. Management:
treatment
of
eczema,
control
of
infections,
and

management
of
bleeding
episodes,
antimicrobial
therapy,
bone

marrow
transplantation,
splenectomy



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 3



D. Requires
bone
marrow
or
stem
cell
transplantation
for
survival

VII.
 Disorders
of
Complement
System

A. Primary

1. Mostly
transmitted
as
autosomal
recessive
traits

2. Can
involve
one
or
more
complement
components


3. Only
supportive
measures
are
available
for
treatment
of
primary

disorders
of
the
complement
system

a. Prevent
bacterial
infection

b. Immunized
with
vaccines
for
S.
pneumoniae,
H.
influenzae,
and
N.

meningitides

B. Secondary

1. Occur
in
persons
with
functionally
normal
complement
systems
because

of
rapid
activation
and
turnover
of
complement
components

as
is
seen

in
immune
complex
disease

2. Reduced
synthesis
of
components

chronic
cirrhosis
of
the
liver
or

malnutrition

3. Hereditary
angioneurotic
edema
and
loss
of
regulation

VIII.
 Phagocytic
Systems

A. Composed
primarily
of
polymorphonuclear
leukocytes
(neutrophils
and

eosinophils)
and
mononuclear
phagocytes
(circulating
monocytes
and
tissue

and
fixed
[spleen]
macrophages)

B. Action
of
these
cells

1. Migrate
to
the
site
of
infection

chemo‐taxis

2. Aggregate
around
the
affected
tissue

adherence

3. Envelope
invading
microorganism

phagocytosis

4. Generate
microbicidal
substances
to
kill
the
ingested
pathogens

C. Dysfunction
of
Phagocytic
System

1. Defect
in
any
of
these
functions
or
a
reduction
in
the
absolute
number
of

available
cells
can
disrupt
the
phagocytic
system

2. Prone
to
infections

a. Bacteria

Candida
species

b. Filamentous
fungi

3. Chronic
granulomatous
disease
(CGD)

a. Primary
disorders
of
phagocytosis

b. Represents
a
group
of
inherited
disorders
that
greatly
reduce
or

inactivate
the
ability
of
phagocytic
cells
to
produce
the
so‐called

respiratory
burst
that
results
in
the
generation
of
toxic
derivatives
of

oxygen
(superoxide
anion
and
hydrogen
peroxide)

creates
an

intracellular
environment
that
kills
ingested
microorganisms

c. Diagnosed
by
examining
the
ability
of
a
person's
phagocytes
to
reduce

a
yellow
dye
to
a
blue
compound
during
active
respiration

d. Treatment

i. Bone
marrow
transplantation

only
cure

ii. Supportive
care

recombinant
interferon‐gamma
and

prophylactic
antibiotic
therapy



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 4



D. Stem
Cell
Transplantation

1. Many
of
the
primary
immunodeficiency
disorders
in
which
the
defect
has

been
traced
to
the
stem
cell
can
be
cured
with
allogeneic
stem
cell

transplantation
from
an
unaffected
donor

a. 
SCID

b. Wiskott‐Aldrich
syndrome

c. Chronic
granulmatous
disease


2. Stem
cells
can
repopulate
the
bone
marrow
and
reestablish

hematopoiesis

a. To
be
effective,
bone
marrow
cells
of
the
host
are
destroyed
by

myeloablative
doses
of
chemotherapy

b. Chronic
immunoglobulin
therapy
may
be
necessary
for
transplant

recipients
who
primarily
retain
B
cells
of
host
origin

3. Stem
cells
can
be
collected
from
the
bone
marrow
or
peripheral
blood

a. HLA‐matched
siblings
usually
produce
the
best
results

b. Stem
cell
aspiration
from
the
bone
marrow
is
the
most
common
form

of
allograft
collection

c. Umbilical
cord

collected
at
the
time
of
delivery
without
producing

detrimental
effects
to
the
mother
and
newborn

IX.
 Adaptive
Immunity

A. Development
of
response
to
antigen

B. Specific
humoral
and
cellular
recognition

C. Memory
cells

X.
 Hypersensitivy
Disorders

A. Excessive
or
inappropriate
activation
of
the
immune
system

B. Types

1. Type
I,
IgE‐mediated
disorders

2. Type
II,
antibody‐mediated
disorders

3. Type
III,
complement‐mediated
immune
disorders

4. Type
IV,
T‐cell‐mediated
disorders

XI.
 Type
I
Hypersensitivity
Reactions

A. IgE‐mediated
reactions

begin
rapidly
5‐30min

B. Allergic
reactions
to
allergens


1. Protein
in
pollen,
house
dust
mites,
animal
dander,
foods,
and
chemicals

like
the
antibiotic
penicillin

2. Exposure
through
inhalation,
ingestion,
injection,
or
skin
contact

3. Reactions
can
be
local
(atopic)
or
systemic

C. Two
types
of
cells
are
central
to
a
type
I
hypersensitivity
reaction

1. Type
2
helper
T
(TH2)
cells
with
two
subsets
of
helper
T
cells

TH1
and

TH2

a. Develop
from
precursor
CD4+
T
lymphocyte

b. TH1
cells


i. Differentiate
in
response
to
microbes

ii. Stimulate
differentiation
of
B
cells
into
IgM‐
and
IgG‐producing

plasma
cells



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 5



c. TH2
cell


i. Differentiation
in
response
to
allergens
and
helminths
(intestinal

parasites)

ii. Stimulate
differentiation
of
B
cells
into
IgE‐producing
plasma

cells,
act
as
growth
factors
for
mast
cells,
and
recruit
and
activate

eosinophils

2. Mast
cells
or
basophils

a. Derived
from
hematopoietic
precursor
cells

b. Contain
granules
that
release
mediators
during
reactions

c. Mast
cells

distributed
throughout
connective
tissue

i. Beneath
the
skin
and
mucous
membranes
of
the
respiratory,

gastrointestinal,
and
genitourinary
tracts,
and
adjacent
to
blood

and
lymph
vessels

surfaces
that
are
exposed
to
environmental

antigens
and
parasites

d. Type
I
hypersensitivity
reactions
begin
with
mast
cell
or
basophil

sensitization

i. Allergen‐specific
IgE
antibodies
attach
to
receptors
on
the
surface

of
mast
cells
and
basophils

ii. With
subsequent
exposure,
the
sensitizing
allergen
binds
to
the

cell‐associated
IgE
and
triggers
a
series
of
events
that
ultimately

lead
to
degranulation
of
the
sensitized
mast
cells
or
basophils,

causing
release
of
their
preformed
mediators

iii. Mast
cells
are
also
the
source
of
lipid‐derived
membrane
products

(e.g.,
prostaglandins
and
leukotrienes)
and
cytokines
that

participate
in
the
continued
response
to
the
allergen

D. Type
I,
IgE‐mediated
hypersensitivity
reaction
process

1. The
stimulation
of
B‐cell

differentiation
by
an
antigen

stimulated
type
2
helper
(TH2)

T
cell
leads
to
plasma
cell

production
of
IgE
and
mast
cell

sensitization

2. Subsequent
binding
of
the

antigen
produces
degranulation

of
the
sensitized
mast
cell
with

release
of
preformed
mediators

that
leads
to
a
primary,
or

early‐phase
response

3. TH2
T‐cell
recruitment
of

eosinophils,
along
with
the

release
of
cytokines
and

membrane
phospholipids
from

the
mast
cell,
leads
to
a

secondary,
or
late‐phase

response



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 6



E. Many
Type
I
hypersensitivity
reactions
have
2
phases

1. Primary
or
initial‐phase
response

occurs
within
5‐30minutes
of

exposure,
subsides
within
60min

a. Vasodilation

b. Vascular
leakage

c. Smooth
muscle
contraction

d. Mediated
by
mast
cell
degranulation

i. Release
of
histamine,
acetylcholine,
adenosine,
chemotactic

mediators,
enzymes
such
as
chymase
and
trypsin
that
lead
to

generation
of
kinins

ii. Histamine

potent
vasodilator

increases
permeability


smooth
muscle
contraction,
bronchial
constriction

systemic

shock

iii. Acetylcholine

bronchial
smooth
muscle
contraction,
dilation
of

small
blood
vessels

iv. Kinins

potent
inflammatory
peptides

activated
by
enzymes


vasodilation
and
smooth
muscle
contraction

2. Secondary
or
late‐phase
response

a. Occurs
about
2
to
8
hours
later
and
lasts
for
several
days

b. More
intense
infiltration
of
tissues
with
eosinophils
and
other
acute

and
chronic
inflammatory
cells

c. Tissue
destruction
in
the
form
of
epithelial
damage

d. Results
from
the
action
of
lipid
mediators
and
cytokines
involved
in

the
inflammatory
response

i. Derived
from
mast
cell
membrane
phospholipids
that
are
broken

down
into
arachidonic
acid

synthesize
into
leukotrienes
and

prostaglandins
that
act
similar
to
histamine
and
acetylcholine
but

with
delayed
and
prolonged
effects

ii. Mast
cells

cytokines,
chemotactic
factors

influx
eosinophils

and
leukocytes

inflammatory
response

e. Plays
a
protective
role
in
the
control
of
parasitic
infections

i. IgE
antibodies
directly
damage
the
larvae
of
these
parasites
by

recruiting
inflammatory
cells
and
causing
antibody‐dependent

cell‐mediated
cytotoxicity

ii. Important
in
developing
countries
where
much
of
the
population

is
infected
with
intestinal
parasites

F. Examples
of
Type
I


1. Anaphylactic
(Systemic)
Reactions

a. Systemic
life‐threatening
hypersensitivity
reaction

b. Characterized
by
widespread
edema,
vascular
shock
secondary
to

vasodilation,
and
difficulty
breathing

systemic
shock

c. Exposure
of
antigen
from
injection,
insect
sting,
skin,
GI
mucosa


level
of
severity
depends
on
the
level
of
sensitization

d. Initial
management:
establishment
of
a
stable
airway
and
intravenous

access,
and
administration
of
epinephrine



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 7



2. Atopic
(local)
Reactions

a. Genetically
determined
hypersensitivity

i. Positive
family
history
of
allergy
is
found
in
about
50%
of
atopic

individuals

ii. Have
high
serum
levels
of
IgE
and
increased
numbers
of
basophils

and
mast
cells.

b. Environmental
allergens
mediated
by
an
IgE‐mast
cell
reaction

c. Most
common
atopic
disorders

urticaria
(hives),
allergic
rhinitis

(hay
fever),
atopic
dermatitis,
food
allergies,
and
some
forms
of

asthma

d. Treatment
for
seasonal
allergy/allergic
rhinitis

desensitization

i. Frequent
(usually
weekly)
injections
of
the
offending
antigens

ii. Antigens,
which
are
given
in
increasing
doses,
stimulate

production
of
high
levels
of
IgG,
which
acts
as
a
blocking
antibody

by
combining
with
the
antigen
before
it
can
combine
with
the
cell‐
bound
IgE
antibodies

XII.
 Type
II
(Cytotoxic)
Hypersensitivity
Reactions

A. Type
II
(antibody‐mediated)
hypersensitivity
reactions
are
mediated
by
IgG

or
IgM
antibodies
directed
against
target
antigens
on
cell
surfaces
or
in

connective
tissues

1. Endogenous
antigens
that
are
present
on
the
membranes
of
body
cells

2. Exogenous
antigens
that
are
adsorbed
on
the
membrane
surface

B. Three
different
types
of
antibody‐mediated
mechanisms

1. Opsonization
and
complement‐
and
antibody
receptor‐mediated

phagocytosis

a. Deletion
of
cells
targeted
by
antibody
can
occur
by
way
of
either
the

complement
system
or
by
antibody‐dependent
cell‐mediated

cytotoxicity
(ADCC),
which
does
not
require
complement

b. Occur
because
the
cells
are
coated
(opsonized)
with
molecules
that

make
them
attractive
to
phagocytes
or
because
of
the
formation
of

membrane
attack
proteins
that
disrupt
the
integrity
of
the
cell

membrane
and
cause
cell
lysis

c. With
ADCC
destruction,
cells
that
are
coated
with
low
levels
of
IgG

antibody
are
killed
by
a
variety
of
effector
cells
that
bind
to
their

target
by
their
receptors
for
IgG,
and
cell
lysis
occurs
without

phagocytosis

d. Examples

i. Mismatched
blood
transfusion
reactions,
hemolytic
disease
of
the

newborn
due
to
ABO
or
Rh
incompatibility

ii. Certain
drug
reactions


o Binding
of
certain
drugs
or
drug
metabolites
to
the
surface
of

red
or
white
blood
cells
elicits
an
antibody
response
that
lyses

the
drug‐coated
cell


o Causes
transient
anemia,
leukopenia,
or
thrombocytopenia,

o Corrected
by
the
removal
of
the
offending
drug



 

Eina
Jane
&
Co.
2009.


 

 Chapter
19:
Disorders
of
the
Immune
Response
 8



2. Complement‐
and
antibody
receptor‐mediated
inflammation

a. When
antibodies
are
deposited
in
the
extracellular
tissues,
such
as

basement
membranes
and
matrix,
the
injury
is
the
result
of

inflammation
rather
than
phagocytosis
or
cell
lysis

b. Deposited
antibodies
activate
complement,
generating
chemotactic

byproducts
that
recruit
and
activate
neutrophils
and
monocytes


released
enzymes
cause
inflammation
and
damage
tissues


glomerulonephritis,
vascular
rejection
in
organ
grafts,
and
other

diseases

c. Goodpasture
syndrome

antibody
binds
to
a
major
structural

component
of
pulmonary
and
glomerular
basement
membranes,

causing
pulmonary
hemorrhage
and
glomerulonephritis

3. Antibody‐mediated
cellular
dysfunction

a. Antibody
binding
to
specific
target
cell
receptors
does
not
lead
to
cell

death,
but
to
a
change
in
cell
function

b. Graves
disease

autoantibody
directed
against
thyroid‐stimulating

hormone
(TSH)
receptors
on
thyroid
cells
stimulates
thyroxine

production,
leading
to
hyperthyroidism

c. Mmyasthenia
gravis,
autoantibodies
to
acetylcholine
receptors
on

the
neuromuscular
endplates
either
block
the
action
of
acetylcholine

or
mediate
internalization
or
destruction
of
receptors,
leading
to

decreased
neuromuscular
function

C. Type
II,
hypersensitivity
reactions

result
from
binding
of
antibodies
to

normal
or
altered
surface
antigens

1. Opsonization
and
complement‐

or
antibody
receptor‐mediated

phagocytosis
or
cell
lysis
through

membrane
attack
complex
(MAC)

2. Complement‐
and
antibody

receptor‐mediated
inflammation

resulting
from
recruitment
and

activation
of
inflammation‐
producing
leukocytes

(neutrophils
and
monocytes)

3. Antibody‐mediated
cellular

dysfunction,
in
which
antibody

against
the
thyroid‐stimulating

hormone
(TSH)
receptor

increases
thyroid
hormone

production

4. Antibody
to
acetylcholine

receptor
inhibits
receptor

binding
of
the
neurotransmitter

in
myasthenia
gravis



 

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Jane
&
Co.
2009.


 

 Chapter
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Response
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XIII.
 Type
III
Immune
Complex
Allergic
Disorders

A. Mediated
by
the
formation
of
insoluble
antigen‐antibody
complexes,

complement
fixation,
and
localized
inflammation

B. Activation
of
complement
by
immune
complex
generates
chemotactic
and

vasoactive
mediators
that
cause
tissue
damage
by
alteration
in
blood
flow,

increased
vascular
permeability,
destructive
action
of
inflammatory
cells

C. Immune
complexes
formed
in
the
circulation
produce
damage
when
they

come
in
contact
with
the
vessel
lining
or
are
deposited
in
tissues,
including

the
renal
glomerulus,
skin
venules,
lung,
and
joint
synovium

1. Vasculitis
seen
in
certain
autoimmune
diseases

2. Systemic
immune
complex
disorders

serum
sickness

a. Triggered
by
the
deposition
of
insoluble
antigen‐antibody
(IgM,
IgG,

and
occasionally
IgA)
complexes
in
blood
vessels,
joints,
and
heart
and

kidney
tissue

b. Most
common
causes:
antibiotics
(especially
penicillin)
and
other

drugs,
various
foods,
and
insect
venom

c. S/S:
urticaria,
patchy
or
generalized
rash,
extensive
edema
(usually
of

the
face,
neck,
and
joints),
and
fever

d. Treatment

removal
of
the
sensitizing
antigen
and
providing

symptom
relief

i. Aspirin
for
joint
pain
and
antihistamines
for
pruritus

ii. Epinephrine
or
systemic
corticosteroids
may
be
used
for
severe

reactions

3. Localized
immune
complex
reactions

Arthus
reaction

a. Localized
tissue
necrosis
(usually
in
the
skin)
caused
by
immune

complexes

b. Produced
by
injecting
an
antigen
preparation
into
the
skin
of
an

immune
animal
with
high
levels
of
circulating
antibody

c. Within
4
to
10
hours,
a
red,
raised
lesion
appears
on
the
skin
at
the

site
of
the
injection

i. Ulcer
often
forms
in
the
center
of
the
lesion

ii. Injected
antigen
diffuses
into
local
blood
vessels,
where
it
comes

in
contact
with
specific
antibody
(IgG)
to
incite
a
localized

vasculitis

D. Type
III,
immune
complex
reactions

involving
complement‐activating
IgG
or

IgM
immunoglobulins
with

1. Formation
of
blood‐borne
immune

complexes
that
are

2. deposited
in
tissues.
Complement

activation
at
the
site
of
immune

complex
deposition

3. leads
to
attraction
of
leukocytes
that

are
responsible
for
vessel
and
tissue

injury




 

Eina
Jane
&
Co.
2009.


 

 Chapter
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of
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Immune
Response
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XIV.
 Type
IV
Hypersensitivity
Reactions

A. Cell‐mediated
rather
than
antibody‐mediated
immune
response

1. Principal
mechanism
of
response
to
a
variety
of
microorganisms,

including
intracellular
and
extracellular
pathogens

2. Can
lead
to
cell
death
and
tissue
injury
in
response
to
chemical
antigens

(contact
dermatitis)
or
self‐antigens
(autoimmunity)

B. Mediated
by
specifically
sensitized
T
lymphocytes

divided
into
two
basic

types

1. Direct
cell‐mediated
cytotoxicity


a. CD8+
cytotoxic
T
lymphocytes
(CTLs)
directly
kill
target
cells
that

express
peptides
derived
from
cystosolic
antigens
that
are
presented

in
association
with
class
I
MHC
molecules

b. Viral
infections

CTL
responses
can
lead
to
tissue
injury
by
killing

infected
target
cells
even
if
the
virus
itself
has
no
cytotoxic
effects

c. CTLs
cannot
distinguish
between
cytopathic
and
noncytopathic

viruses

kill
virtually
all
infected
cells
regardless
of
whether
the

infection
is
harmful

d. Hepatitis

the
destruction
of
liver
cells
is
due
to
the
host
CTL

response
and
not
the
virus

2. Delayed‐type
hypersensitivity

a. Occur
in
response
to
soluble
protein
antigens
and
primarily
involve

antigen‐presenting
cells
such
as
macrophages
and
CD4+
helper
T
cells

of
the
TH1
type

b. During
the
reaction
TH1
cells
are
activated
and
secrete
an
array
of

cytokines
that
recruit
and
activate
monocytes,
lymphocytes,

fibroblasts,
and
other
inflammatory
cells

c. Require
the
synthesis
of
effector
molecules
and
take
24
to
72
hours
to

develop,
which
is
why
they
are
called
“delayed‐type”
hypersensitivity

disorders

i. Best‐known
DTH
response
is
the
reaction
to
the
tuberculin
test,
in

which
inactivated
tuberculin
or
purified
protein
derivative
is

injected
under
the
skin
 
area
of
redness
and
induration

develops
within
8
to
12
hours,
reaching
a
peak
in
24
to
72
hours

ii. Allergic
contact
dermatitis


o Inflammatory
response
confined
to
the
skin
that
is
initiated
by

reexposure
to
an
allergen
to
which
a
person
had
previously

become
sensitized

o Erythematous,
papular,
and
vesicular
lesions
associated
with

intense
pruritus
and
weeping

o Affected
area
often
becomes
swollen
and
warm,
with

exudation,
crusting,
and
development
of
a
secondary
infection

o Severity
of
the
reaction
associated
with
contact
dermatitis

ranges
from
mild
to
intense



 

Eina
Jane
&
Co.
2009.


 

 Chapter
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Immune
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o Because
this
condition
follows
the
mechanism
of
a
DTH

response,
the
reaction
does
not
become
apparent
for
at
least

12
hours
and
usually
more
than
24
hours
after
exposure

o Diagnosis:
patch
test

o Treatment

 Remove
irritant

 Topical
preparations

ointments,
corticosteroid
creams

to
relieve
symptomatic
skin
lesions
and
prevent
secondary

bacterial
infections


 Severe
reactions

systemic
corticosteroids

iii. Hypersensitivity
pneumonitis

o Exposure
to
inhaled
organic
dusts
or
related
occupational

antigens

o Involve
a
susceptible
host
and
activation
of
pulmonary
T
cells,

followed
by
the
release
of
cytokine
mediators
of
inflammation

o Produces
labored
breathing,
dry
cough,
chills
and
fever,

headache,
and
malaise

o “Farmer's
lung,”
a
condition
resulting
from
exposure
to
moldy

hay

o Diagnosis:
obtain
a
good
history
(occupational
and
otherwise)

of
exposure
to
possible
antigens

o Treatment
consists
of
identifying
and
avoiding
the
offending

antigens
or
systemic
corticosteroids


C. 



 

Eina
Jane
&
Co.
2009.


 

 Chapter
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Disorders
of
the
Immune
Response
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XV.
 Hypersensitivity
Reactions

A. Exposure
to
latex
may
occur
by
cutaneous,
mucous
membrane,
inhalation,

internal
tissue,
or
intravascular
routes

1. Most
severe
reactions
have
resulted
from
latex
proteins
coming
in

contact
with
the
mucous
membranes
of
the
mouth,
vagina,
urethra,
or

rectum

condoms

2. Allergic
reactions
to
latex
products
can
be
triggered
by
the
latex
proteins

or
by
the
additives
used
in
the
manufacturing
process

a. Cornstarch
glove
powder
has
an
important
role
in
the
allergic

response

latex
proteins
readily
absorbed
by
glove
powder
and

become
airborne
during
removal
of
the
glove

b. High‐exposure
areas
such
as
operating
rooms
where
powdered
gloves

are
used
contain
sufficiently
high
levels
of
aerosolized
latex
to

produce
symptoms
in
sensitized
persons

B. Type
of
Latex
Allergies

1. Type
I,
IgE‐mediated
hypersensitivity
reaction

a. Occur
in
response
to
the
latex
proteins

b. Urticaria,
rhinoconjunctivitis,
asthma,
or
anaphylaxis

c. Diagnosis:
serum
IgG
levels

2. Type
IV,
T
cell
mediated
response

a. Most
common
type
of
reaction

b. Contact
dermatitis
usually
develops
48
to
96
hours
after
direct

contact
with
latex
additives

affects
the
dorsum
of
the
hands
and
is

characterized
by
a
vesicular
rash

glove
contact
is
continued,
the

area
becomes
crusted
and
thickened

c. Diagnosis:
serum
TH1


C. Treatment

1. Avoiding
latex
exposure,
medical
bracelet,
skin
moisturizer

2. Use
of
powder‐free
gloves
can
reduce
the
amount
of
airborne
latex

particles

3. Health
care
workers
with
severe
and
life‐threatening
allergy
may
be

forced
to
change
employment

4. All
surgical
or
other
procedures
on
persons
with
latex
allergy
should
be

done
in
a
latex‐free
environment
in
which
no
latex
gloves
are
used
in
the

room
or
surgical
suite
and
no
latex
accessories
(e.g.,
catheters,
adhesives,

tourniquets,
and
anesthesia
equipment)
come
in
contact
with
the
patient



 

Eina
Jane
&
Co.
2009.


 

 Chapter
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of
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Immune
Response
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D. 

XVI.
 Transplantation
Immunopathologies

A. Process
of
taking
cells,
tissues,
or
organs,
called
a
graft,
from
one
individual,

and
placing
them
into
another
individual

B. The
individual
who
provided
the
tissue
is
called
the
donor,
and
the
individual

who
receives
the
graft
is
called
either
the
recipient
or
the
host

C. Rejection:
process
in
which
the
recipient's
immune
system
recognizes
the

graft
as
foreign
and
attacks
it

D. Types
of
transplants

1. Allogenic

donor
and
recipient
are
related
or
unrelated
bu
share
similar

HLA
types

2. Sygeneic

donor
and
recipient
are
identical
twins

3. Autologous

donor
and
recipient
are
the
same
person

E. Cell
surface
antigens
that
determine
whether
the
tissue
of
transplanted

organs
is
recognized
as
foreign
are
the
MHC
or
human
leukocyte
antigens


Major
Histocompatibility
Complex

1. Lymphocyte
recognition

2. Antigen
presentation

3. Control
the
immune
response
through
recognition
of
self
and
nonself

4. The
more
different
they
are,
the
higher
chance
the
body
will
reject
the

donor



 

Eina
Jane
&
Co.
2009.


 

 Chapter
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Immune
Response
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F. Rejection
is
a
complex
process
that
involves
cell‐mediated
immunity
and

circulating
antibodies

G. Basic
Patterns
of
Transplant
Rejection

1. Hyperacute
reaction

a. Occurs
almost
immediately
after
transplantation

b. Produced
by
existing
recipient
antibodies
to
graft
antigens
that

initiate
a
type
III,
Arthus‐type
hypersensitivity
reaction
in
the
blood

vessels
of
the
graft

c. Antibodies
usually
have
developed
in
response
to
previous
blood

transfusions,
pregnancies
in
which
the
mother
makes
antibodies
to

fetal
antigens,
or
infections
with
bacteria
or
viruses
possessing

antigens
that
mimic
MHC
antigen

d. Very
very
rare

mismatch,
serious
complication
problem
with

sample
handling
(human
error)

2. Acute
rejection

a. Occurs
within
the
first
few
months
after
transplantation
and
is

evidenced
by
signs
of
organ
failure

b. May
occur
suddenly
months
or
even
years
later,
after

immunosuppression
has
been
used
and
terminated

c. T
lymphocytes
play
a
central
role
in
acute
rejection,
responding
to

antigens
in
the
graft
tissue

activated
T
cells
cause
direct
lysis
of

graft
cells
and
recruit
and
activate
inflammatory
cells
that
injure
the

graft

d. Can
be
controlled
by
immunosuppressant
therapy

e. Type
IV
reaction

3. Chronic
rejection

a. Occurs
over
a
prolonged
period

b. Manifests
with
dense
intimal
fibrosis
of
blood
vessels
of
the

transplanted
organ

c. Renal
transplant

characterized
by
a
gradual
rise
in
serum

creatinine
over
a
period
of
4
to
6
months

d. Common

XVII.
 Graft‐Versus‐Host
Disease

A. Occurs
when
immunologically
competent
cells
or
precursors
are

transplanted
into
recipients
who
are
immunologically
compromised

B. Involves
activated
CD4+
and
CD8+
T
cells
with
ultimate
generation
of
a
type

IV,
cell‐mediated
DTH
and
CTL
reactions

C. Three
basic
requirements
are
necessary
for
GVHD
to
develop

1. Transplant
must
have
a
functional
cellular
immune
component

2. Recipient
tissue
must
bear
antigens
foreign
to
the
donor
tissue

3. Recipient
immunity
must
be
compromised
to
the
point
that
it
cannot

destroy
the
transplanted
cells

D. Acute
GVHD

1. Develops
within
days
to
weeks
after
transplantation

2. Involves
the
epithelial
cells
of
the
skin,
liver,
and
gastrointestinal
tract



 

Eina
Jane
&
Co.
2009.


 

 Chapter
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Immune
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a. Skin

development
of
a
pruritic,
maculopapular
rash,
which
begins

on
the
palms
and
soles
and
frequently
extends
over
the
entire
body,

with
subsequent
desquamation

b. Gastrointestinal
symptoms
include
nausea,
bloody
diarrhea,
and

abdominal
pain

c. Liver

painless
jaundice,
hyperbilirubinemia,
and
abnormal
liver

function
test
results

i. Progress
to
development
of
veno‐occlusive
disease,
drug
toxicity,

viral
infection,
iron
overload,
extrahepatic
biliary
obstruction,

sepsis,
and
coma

ii. Veno‐occlusive
disease

obliteration
of
the
small
hepatic
veins

and
venules

centrilobular
congestion
and
hepatocellular

necrosis

E. Chronic
GVHD

1. When
symptoms
persist
or
begin
100
days
or
more
after
transplantation

2. May
follow
acute
GVHD
or
it
may
develop
insidiously

3. Develop
skin
lesions
resembling
systemic
sclerosis
and
manifestations

mimicking
other
autoimmune
diseases

F. Treatment

block
any
of
the
3
steps
of
pathogenesis

T
cell
activation
and

action
of
cytokines

1. Immunosuppressive
drugs

cyclosporine,
tacrolimus


2. Anti‐inflammatory
drugs

or
glucocorticoids

XVIII.
 Autoimmune
Disease

A. Self‐tolerance

ability
of
the
immune
system
to
differentiate
self
from

nonself


1. HLA
antigens
encoded
by
MHC
genes
that
serve
as
recognition
markers
of

self
and
nonself
for
the
immune
system

2. Autoimmunity
results
from
loss
of
self‐tolerance

B. Systemic

1. Mixed
connective
tissue
disease

2. Polymyositis‐dermatomyositis

3. Rhematoid
arthritis

4. Scleroderma

5. Sjögren
syndrome

6. Systemic
lupus
erythematosus

C. Blood

1. Autoimmune
hemolytic
anemia

2. Autoimmune
neutropenia
and
lymphopenia

3. Idiopathic
thrombocytopenic
purpura

D. Other
organs

1. Acute
idiopathic
polyneuritis

2. Atrophic
gastritis
and
pernicious
anemia

3. Autoimmune
adrenalitis

4. Goodpasture
syndrome

5. Hashimoto
thyroiditis



 

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Jane
&
Co.
2009.


 

 Chapter
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Immune
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6. Type
1
DM

7. Myasthenia
gravis

8. Premature
gonadal
(ovarian)

9. Primary
biliary
cirrhosis

10. Sympathetic
opthalmia

11. Temporal
arteritis

12. Thyrotoxicosis
(Graves
disease)

13. Crohn
disease,
ulcerative
colitis

E. Mechanisms
of
autoimmune
disease

1. Inheritance
of
susceptibility
genes
that
contribute
to
the
maintenance
of

self‐tolerance


2. Gender


a. SLE
occur
more
commonly
in
women
than
men,
suggesting
that

estrogens
may
play
a
role
in
the
development
of
autoimmune
disease

b. Estrogens
stimulate
and
androgens
suppress
the
immune
response

3. Environmental
factors
that
promote
the
activation
of
self‐reactive

lymphocytes

a. Infectious
agents

b. Breakdown
of
T‐cell
anergy
(state
of
unresponsiveness
to
antigen)


prolonged
or
irreversible
inactivation
of
lymphocytes,
such
as
that

induced
by
an
encounter
with
self‐antigens

4. Failures
of
Self
tolerance

a. Disorders
in
MHC‐antigen
complex‐receptor
interactions

b. Molecular
mimicry

microbe
shares
an
immunologic
epitope
with

the
host

c. Super
antigens

family
of
substances
able
to
short‐circuit
the

normal
sequence
of
events
in
an
immune
response,
leading
to

inappropriate
activation
of
CD4+
helper
T
cells

F. Summary

Autoimmune diseases represent a disruption in self-tolerance that results in damage to
body tissues by the immune system. Autoimmune diseases can affect almost any cell or
tissue of the body. The ability of the immune system to differentiate self from nonself is
called self-tolerance. Normally, self-tolerance is maintained through central and
peripheral mechanisms that delete autoreactive B or T cells or otherwise suppress or
inactivate immune responses that would be destructive to host tissues. Defects in any of
these mechanisms could impair self-tolerance and predispose to development of
autoimmune disease.

The ability of the immune system to differentiate foreign from self-antigens is the
responsibility of HLA encoded by MHC genes. Antigen is presented to receptors of T
cells in combination with MHC molecules. Among the possible mechanisms responsible
for development of autoimmune disease are failure of T-cell-mediated immune
suppression; aberrations in MHC-antigen-TCR interactions; molecular mimicry; and
superantigens. The suggested criteria for determining that a disorder results from an
autoimmune disorder are evidence of an autoimmune reaction, determination that the
immunologic findings are not secondary to another condition, and the lack of other
identifiable causes for the disorder.


 

Eina
Jane
&
Co.
2009.