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7-23-1992
Rheumatoid arthritis and myasthenia gravis as
examples of autoimmune diseases
Michael Collins
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ROCHESTER INSTITUTE OF TECHNOLOGY
A Thesis Submitted to the
Fine
and
Applied Arts in
Faculty of The College of
Candidacy for the Degree of
MASTER OF FINE ARTS
Rheumatoid Arthritis
Examples
of
and
Myasthenia Gravis
Autoimmune Diseases
By
Michael Collins
7/23/92
as
Approvals
Advisor: G. Hintz
Associate Advisor: B. Cole
Date:
Associate Advisor: Dr. D. Merrill
Date:
7- 3/- 92..
Associate Advisor: R. Wabnitz
Date:
g-)7· <J;Z
~n ~
R. Roger Remington
Special Assistant to the Dean for Graduate Affairs: Po BerReRA
Date:
1"//' I"
"'2.,-
Dean, College of Imaging Arts and Sciences: M. Lucas
Date:
7-8'--(6
I, Michael Collins
, hereby grant permission to the Wallace
Memorial Library of RIT, to reproduce my thesis in whole or in part. Any
reproduction will not be for commercial use or profit.
Date:
7/ z '6/ 'f z.
Introduction
is
Autoimmunity
individual's
own
an
inappropriate immune
healthy body
diseases have been identified,
Some
ways.
are
broad ranging in
One
disease
and
very specific to
they
blocked
weakening
muscle
is inhibited.
disorder is
of
and
degraded
the patient's
by
limbs,
feature
of
this
Accompanying
articular cartilage and
the bone beneath it.
focus
examples of autoimmune
undergraduate
the
In
order
to properly
result
is
a
The
rheumatoid arthritis.
the
of
synovial
joints
the inflammation is the destruction
diseases.
It
consists of
use would
be
textbook on immunology.
cellular and chemical
skeletal
of
upon rheumatoid arthritis and myasthenia gravis as
Their intended
illustrations.
the
as nervous stimulation of the
throughout the body.
will
of
The
antibodies.
is inflammation
condition
This
myasthenia gravis.
disease is
example of an autoimmune
This thesis
different tissues in different
scope.
gradual
predominant
affect
of autoimmune
variety
the neuromuscular junction. The receptors
muscle cells are
Another
wide
particular organs, while others are more
example of an autoimmune
affects
A
tissues.
response against an
interactions
understand
of
twelve full
as reproductions
I have
chosen
color
in
an
to concentrate
upon
these pathologies.
the pathophysiology of an autoimmune
condition, a full discussion of the normal immune response is necessary to
provide
background.
provokes an
immune
This discussion begins
response.
The immune
task of monitoring all internal regions of the
When a foreign
substance
is detected, it is
1
with a
definition
system
body
is
charged with
for foreign
attacked
by
of what
an
the
substances.
immune
response.
The
normal
immune
supposed to
system
be in the
from
body
substance; in other words, it
molecule which
order
for
can
a molecule
a
a
foreign
an
Dictionary
of
healthy
and
distinguish
inducing
capable of
(The New Penguin
antigen
In
is
distinguishes
structure that
is
potentially threatening
"self"
from
immune
"non-self."
response
Any
is termed
Biology, 1990).
to provoke an immune response, a
"read"
by
The
either
determinant (Barrett 1988, 38; Tizard 1988,
interact
which will
The
antigenic
directly
determinants
an
such as a
is
with
the immune
determinants
instructions. The group
When
of genes which
is
of self antigens
immune
response
bacterium, it is
single
called
is
bacterium,
each
and pollen grains are
insulting
substance
originate
from
is the
part of
in
antigen
accordance with genetic
defines the distinctive
the
the
system.
major
antigenic
histocompatibility
invading
mounted against an
determinants
complex.
organism,
Rather, it
the molecules
on
the
immune
which
response
body
cells of
in
an
the
(Tizard 1988, 30).
two other common sources of antigens.
foreign
antigen
it is
not
necessary for the
Cancer
cells
and, if significantly different from normal cells,
as foreign and attacked
germinal event
body by
as a
an
to originate from outside the body.
within
be interpreted
foreign
and
or antigenic
not mounted against the entire organism.
provoking
However, to be identified
The
the epitope
the bacterium. There may be a variety of different antigens upon a
Viruses
will
18)
are structured
mounted against various antigenic
compose
code
the immune system and interpreted as foreign. This precise
the antigenic molecule is called
portion of
it
portion of
must consist of a series of chemical elements which act as a code.
is
an
immune
(Fig. 1).
response
is
phagocytosis of
mononuclear phagocytic system
the
(MPS). The
mononuclear phagocytic system
and
is
composed
Macrophages
entirely
may be known
lining
of mature macrophages
by
of spleen sinusoids and
another name when
example, a macrophage
4).
a component part of
found throughout the body, but
are
in the lung, liver,
is
Macrophages
within
A
they
migrate
macrophage
blood vessel,
attracted
against
the
Once
antigen
to
into tissues
may
and wait
an antigen
chemicals
for
keep it
in the
are antibodies,
linkage
lymph
node.
particular
prevalent
Macrophages
For
tissues.
as macrophages
itself to
an antigen.
a
the bone
monocytes.
,
marrow and
When they
are
(Barrett 1988, 86).
free surface,
such as
the
lining
of a
Alternatively, it may be chemically
from some distance away, in
is detected, the
which case
macrophage will endeavor
it
will move
to bind the
from getting away (Barrett 1988, 100). Opsonins
body
which coat antigens
fibronectin,
antigens and then
Some
examples of opsonins
and the complement protein
lock into
makes attachment of
C3b. Opsonins
receptors upon macrophages.
the macrophage to the
are
by
to make attachment
macrophages or other phagocytic cells easier.
bind to
particularly
antigen.
an antigen
to
adhere
are
promonocytes within
then drift through the circulatory system as
mature
(Roitt 1991, 4).
the liver is termed a Kuppfer Cell (Roitt 1991
from
originate
found in
the immune system,
This
antigen much more
efficient.
There is
a
tendency for
on a negative charge
cell
in
have
negative
attachment
1988,45).
by
particles or cells suspended
(Tizard 1988, 43).
charges,
they
neutralizing any
If both the
in
body
fluids to take
antigen and phagocytic
will repel each other slightly.
negative charge on
the
Opsonins
antigen
(Tizard
aid
After the
is accomplished, the
attachment
it
antigenic substance and seals
the
macrophage surrounds
The
within a vacuole.
towards the macrophage's center while lysosomes
antigen
is
moved
to kill it
provide enzymes
(Barrett 1988, 101).
Another
Humoral
part of
immunity
the immune system is
involves
antibodies
what
is
circulating in
Medical Desk Dictionary, 1986). An antibody is
molecule, produced in response to an
globulin
There
and
five distinct
are
best
studied
weight of
classes of
is the IgG
150,000 daltons,
One pair, the
antigen
antigen
or a
(Barrett 1988, 25).
most well-known
a molecular
and consists of two pairs of polypeptide chains.
one end, the
parallel and
heavy
bound together
chains
ends of
(Keeton 1986, 775). Antibodies play a
the
by
"Y"
diverge, forming
upper segments of
It is the top two
side.
immunoglobulin,
(Barrett 1988, 48). IgG has
Adjacent to both divergent
chain, one on each
an
fluids (Webster's
body
immunoglobulins. The
pair, is arranged in
heavy
disulfide bonds. Towards
shape.
class
humoral immunity.
called
"Y"
the
shape
a
is
"Y"
shape which
central role
a
light
bind
in the immune
response, so it may not be surprising that antibodies play a central role in
many
autoimmune
Plasma
diseases.
the
cells are
from B-lymphocytes,
are a type of white
producers of antibodies.
as part of
blood
with one specific antigen.
cell except
antigen
that one
No
other antigen will
bringing
(Tizard 1988, 202).
scattered across
response
cells are
derived
(Fig. 2). B-lymphocytes
Each B-cell is specifically designed to
particular antigen
is the first step in
plasma cell
cell.
the immune
Plasma
for
about
which
the
have any
it is
effect upon a B-
specific.
maturation of
react
Contact
with an
the B-cell into a
B-cells have immunoglobulin molecules
their surface to act as antigen receptors (Barrett
4
1988, 116).
B-cells
are to
differentiate. A
the helper
T-cell, is
it
presented to
in
order
by
cell which mediates the
sometimes necessary.
a
they
immune response, known
Helper T-cells
cell, such as a macrophage,
with
must
MHC
have
class
II
and
lymphokines. These lymphokines include B-cell
B-cell differentiation factor
promoting the
maturation of
Helper T-cells
also secrete a
B-cells to
molecules
effectiveness of macrophages
There
lymphokines
classified as
without
the
help
of which assist
factor
in
which
increase the
(Tizard 1988, 244).
are some antigens which will provoke
differentiation
growth
T-
(Tizard 1988, 204).
plasma cells
of
variety
(BCDF), both
as
antigen
for it to activate (Sheehan 1990, 31). Once activated, the helper
cell produces
(BCGF)
than just contact with antigen if
will sometimes require more
activation and
helper T-cell. These antigens
of a
T-cell independent
B-cell
antigens
are
(Sheehan 1990, 34).
Myasthenia Gravis
Myasthenia
characterized
include
gravis
by
is
an autoimmune
increased
fatigability
slurred speech, nasal voice,
proximal extremities.
The
condition
(Bullock 1992, 1092). The
receptors of
the
specific
neuromuscular
Each individual
does
nerve
not
physically
lies
within an
contact
most
focus
the
comes
the
is chiefly
of skeletal muscle.
drooping
is
which
of
Typical
symptoms
eyelids and weakness of the
commonly
seen
in young
adults
the disease is the acetylcholine
junction.
muscle cell of
innervation. This innervation
disease
body
requires
from a branch
muscle cell.
indentation in the
direct
nervous
of a nerve
fiber
Rather, the terminal
muscle
which
end of
the
cell, called the neuromuscular
synaptic cleft
surrounded
(Fig. 3). The terminal
by
end of the neuron
the muscle cell. The terminal end
small portion of the muscle cell which encircles
plate.
gap
may
The
neuron
(Ross, Reith
stimulate the muscle to contract
The
across the synapse to
bind
is
subneural clefts.
The
to
regions of this
between the
The
.5
Angstrom units,
with
These
allowing
muscle cell.
be
This
ions
propagated
to
open
into the
along the
1991, 71). When the
is broken
cell.
muscle
form high
(Ross,
acetylcholine receptors are
of
units of
the muscle
Their total
it appearing
on
1987, 296).
in the
binds to them,
electrical charge of
of
and stimulate
it to
the
the muscle cell
If strong enough, a shift in polarity
fiber
by
these junctional folds are the
only 4 Angstrom
neuron releases
more acetylcholine than
acetylcholine
surface
the
between the synaptic cleft and the interior
causes a change
stream
which
the junctional folds
receptors change shape when acetylcholine
a channel
as sodium
neuron across
units at their widest points.
the exterior of the muscle cell (Salpeter
nerve
muscle.
surface which
(Seybold 1991, 77). The
7.8 Angstrom
receptors are
height is 11
the
that are embedded in the bilipid membrane
protein molecules
a small
crevices are termed
subneural clefts are called
acetylcholine receptors
cell.
These
upon
by
acetylcholine,
Rather, the
undulating
Reith and Romrell 1989, 210). Located
muscle
Romrell 1 989, 208). The
faces the
each other.
completely
called the motor end
with receptors on
not a smooth concave surface.
creases arranged parallel
plateaus
and
by releasing
surface of the muscle cell which
synapse
it is
almost
the neuron and the
is separated from actually touching
called the synaptic cleft
diffuses
of
is
contract
will
(Seybold
acetylcholine, it usually releases
is necessary to depolarize
a muscle.
However,
is normally broken down very quickly into its two component
6
This breakdown is implemented
parts: acetic acid and choline.
enzyme
cholinesterase,
(Seybold 1 991
back to the
In the
immune
a substance
71 ). After this transpires, the
,
neuron
known
causes this unfortunate event
antigenic
is
at
determinants
which are
(Vincent 1990, 182). Thus, the
for
remains undetermined.
making for
may
gamma and
a total of
located
sites
not
on
other
is
locations
binding
The
5
subunits
the two alpha
site.
on
similar
enter
to
binds
what
the
body
possessing
acetylcholine receptors
in the ensuing immune
(Fig. 5). Of
positive
all
for circulating
(Seybold 1991, 72).
of acetylcholine
to the receptors
,
These have been designated
71).
alpha component
is
repeated
twice,
(Salpeter 1987, 296). Acetylcholine binds to
components.
binding
to bind.
Blockage
of
this
to the identical spot
In the majority
binding
site
where
of cases antibodies
bind to
the receptor, but overlap and block the acetylcholine
This is
called steric
acetylcholine.
could prevent
the
It has been
hindrance (Drachman
et al.
Alternatively, the antibody may bind directly to the location
which
Exactly
acetylcholine receptors
binding
delta. The
supposed
by
receptors are composed of subunits arranged
be due to the antibody
acetylcholine
the
barrel (Seybold 1991
staves of a
may
acetylcholine receptors
How the antibody blocks the
beta,
very
unclear.
Myasthenia gravis, 90% test
patients with generalized
alpha,
this time
antibodies generated
response would cross react with
like
acetic acid and choline move
acetylcholine receptors.
some unknown antigen
antibodies specific
synapse
as myasthenia gravis, antibodies produced
block and degrade
hypothesized that
the
to be reabsorbed and reconstituted (Fig. 4).
condition
system
in the
present
normally
by
the opening
Or, it may bind
of
to the
receptor
1987, 93).
on
in
a
the receptor
way
the central ionic channel (Seybold
which
1991, 72).
Acetylcholine
10 to 14 days
receptors are
they
(Tizard 1 988, 523). The formation
may disrupt the
disease
receptors
ability
of
antibody
tiny
clusters on
the
cross
membrane
bind to
linked
enzymatically degraded
(Drachman
et al.
1987, 92; Dixon
can now comprehend
impeded from stimulating the
Acetylcholine is
released
by
contract.
they
the
time.
drawn together into
are endocytosed
fibers
during
of nervous
impulses is
myasthenia gravis.
synapse.
However,
the total
antibodies as well as complement-mediated
damage
result
is
receptors.
Therefore,
not enough
ions
the muscle to occur, and the muscle
abnormal muscle weakness and
and
fatigability
are
will not
(Bullock
1992, 1092).
There is
available.
no cure
for
myasthenia
This usually begins
with
gravis, but effective treatments are
dosages
medications, such as pyridostigmine
8
6)
Fisher 1983, 277).
receptor
of
in
from lysosomes (Fig.
how the transmission
muscle
the
to the
number of
This is due to
for depolarization
The
with
process relies on
with enzymes
and
degrade the
also
antibodies and
normally into the
accelerated endocytosis of
released
interfere
more than one antigen at a
numbers of receptors available are reduced.
blockage from
membrane attack
process contributes
This
surface, where
groups and
One
may
their endocytosis.
molecules to
Receptors may become
into
(Seybold 1991, 72).
receptor antibodies
by accelerating
this
which
Every
cell.
complement proteins
muscle cell's membrane and
remains controversial
Anti-acetylcholine
blood
of complement
The degree to
receptor replacement.
fixing
the muscle
Antibodies bound to
are endocytosed and replaced.
acetylcholine receptors are capable of
complexes
by
recycled
constantly
of anticholinesterase
bromide,
ambenonium chloride or
neostigmine
bromide (Seybold 1991, 84). These
from
enzyme cholinesterase
and choline.
With
extra
breaking
intact
dosage
be
will
of
into
bind to the
may
cause
acetic acid
more
increased
likely
Hence,
neurotransmitter.
However,
sufficient to cause muscle contraction.
of anticholinesterase
desensitization
will
acetylcholine
in the synapse, it is
acetylcholine
that the few receptors remaining
depolarization
down
inhibit the
medications will
fatigability
the postsynaptic membrane (Seybold 1991
,
over
due to
Other
96).
therapies include corticosteroids, plasmapheresis and azathioprine
(Seybold 1991
,
86).
In 12%
of all
cases, hyperplasia of the thymus is
evident, sometimes requiring thymectomy. The prognosis for patients
myasthenia gravis
with
utilizing the
the caveat that
activities
current therapies available
they may be
required
with
is generally good,
to avoid extremely
fatiguing
(Seybold 1991, 84).
Rheumatoid Arthritis
The
most common clinical manifestations of rheumatoid arthritis are pain
and
swelling
feet
are
of
joints in the
the most
likely
extremities.
The
of
flare-ups
common
between aging and the
Studies
of twins and
Some
of
of
the hands and
the
knees,
ankles,
patients experience
and remissions, while others endure a constant attack
fluctuating intensity (Samter
three times more
joints
to be affected, but involvement
elbows, wrists and hips are not infrequent.
occasional
small
in
et al.
women
frequency
familial
predisposing individuals to
of
1988, 1365). Rheumatoid
than men.
developing
9
a
direct
the disease (Samter et al.
groups show
1988, 1367).
There is
arthritis
is
correlation
1988, 1366).
that genetic factors play a role in
rheumatoid arthritis
(Samter
et al.
The
joints
synovial
healthy
bones
a
the
region of
to
are covered with
matrix
hyaline
Hyaline
cartilage.
surrounding
small
surfaces of
cartilage
dispersed
in
body
define the anatomy
briefly
joint (Fig. 7). First, the articulating
synovial
homogeneous
typically involved
Therefore, it is necessary
rheumatoid arthritis.
of a
are a
is
the
composed of
Within these lacunae live chondrocytes,
which are specialized cells
responsible for the production of matrix.
The
matrix
1989, 124). The
point of the
collagen
are
formed like
composed of
and
Romrell
the highest
archways with
free articulating
two
the two
surface and
the archway down adjacent to the bone (Weiss 1983, 251).
fiber
arrangement can also
dimensional felt-like
composed of
fibrils
adjacent to the
archway
anchor points of
The
collagen
is
(Ross, Reith
materials, collagen fibrils and ground substance
lacunae.
spaces called
The
pattern.
be
to a three
compared
ground substance of
hyaline
cartilage
proteoglycans, glycosaminoglycans and glycoproteins
is
(Ross,
Reith and Romrell 1989 123).
Surrounding
the joint is a capsule of connective tissue called the joint
capsule.
The
filled
fluid. The joint
with
dense
the
and
area enclosed
loose
synovial
by
the capsule is called the joint space and it is
capsule
is
connective tissue.
vascularized
The interior
tissue,
lining
These
phagocytic
type B.
space
the joint capsule is
synoviocytes are categorized
types. The first type is simply a precursor for the other
The
cell.
of
two,
and
into three
is
called a
second sort of synoviocyte exhibits macrophage-like
behavior and is known as the type A cell. The last
It is
both
membrane, composed of a one to three layer thick surface of
cells termed synoviocytes.
type C
composed of
responsible
(Firestein, Tsai
for the
and
secretion of
the fluid
Zvaifler 1987, 449).
10
which
cell
is
called
fills the joint
There
into the joint
First, the
space.
fenestrated. Also, the layers
between them
membrane
Zvaifler
The
antigen which
rheumatoid arthritis
long
chain of events
(Utsinger,
This
body
and provokes an
damage may be due to
alteration of
as
immune
reaction.
reaction are somehow
an enzyme
in the
inflammatory
the antibody molecule reveals a new antigenic
Some genetically
response against
known
been identified. It is believed that this
not yet
the antibodies produced in the immune
determinant.
immune
highly
true basement
and the adjacent connective tissue
initiates the
has
Possibly this
process.
capillaries within the joint capsule are
of synoviocytes possess no
unidentified antigen enters the
altered.
substances to pass
Ehrich 1985, 153).
and
However,
it easy for
are two characteristics which make
predisposed
individuals
will mount an
this newly created antigen, generating antibodies
against antibodies, or rheumatoid
factor (Fig.
8) (Utsinger,
Zvaifler
and
Ehrich 1985, 152).
Hence,
these antigenic antibodies
rheumatoid
factor
tend to settle
Zvaifler
and
activate
the
and
form immune
within soft connective
will
become chemically bound to
complexes.
These immune
tissues and hyaline cartilage
complexes
(Utsinger,
Ehrich 1985, 151). As immune complexes aggregate,
complement cascade
in
what
is
called a
type III
they
hypersensitivity
(Tizard 1988,490).
Current dogma breaks
rheumatoid arthritis
exudative phase and chronic phase.
polymorphonuclear
cells
The
the joint
capsule.
immune
cells within
in the joint
The
down into two
exudative phase
space and changes
chronic phase centers upon
the joint capsule (Ziff
11
phases:
the
is focused
on
in the
cells
lining
interactions between
1990, 127).
Blood
proteins and cellular
histological
vascular
a synovial
joint is
cells around the small
before releasing digestive
location
ideal. The
of
with
into the
synovial
joints to
(Fig. 9).
neutrophils
first
engulf
the immune
complex
(Tizard 1988, 44). Unfortunately, the
enzymes
immune
of aggregated
infiltration
complement will act as a
chemotactic agent for neutrophils, which then move
Under ideal conditions,
observable
the capsule, along
vessels of
dilation (Samter 1988, 1369). Blood
phagocytose the antigen complexes
The first
region.
perivascular
blood
serum
permeability allowing
blood elements into the
in
change
inflammatory
vessel
increase
complement will
in
complexes
rheumatoid arthritis
hyaline
complexes often settle within
cartilage.
is far from
This is
understandable, considering that between 60 to 78 percent of hyaline
cartilage's net weight
most of this water
such as
is
is bound,
(Ross, Reith
some
immune complexes, to
neutrophils are unable
but may
water
still
be
able
to
and
is bound
so
Romrell 1989, 123). Though
loosely
as to allow materials,
the cartilage matrix.
settle within
Therefore,
to internalize the sequestered immune complexes,
make contact and
bind
with
them.
Under these
circumstances, neutrophils release the contents of their lysosomes
onto
the
cartilage.
These
contents
include
collagenase which
may damage the
and proteoglycans
(Fig.
Another
complication
involving
contents which occurs upon cell
neutral proteinases and
cartilage
10) (Roitt 1991,
by degrading
causing
more edema
collagen
fibrils
333).
neutrophils
is the
release of cellular
death. These contents include kininogens
and vasoactive amines which promote vascular
enzymes promote mast cell
directly
degranulation
(Utsinger, Zvaifler
12
of
and
dilation
histamine
and edema.
when
Other
released, thus
Ehrich 1985, 154). Also, type A
cells of the synovial
inflammatory
lining
phagocytose
in the process.
mediators
immune complexes, releasing
They
release enzymes such as
acidic and neutral proteinase which attack proteoglycan
and
(Utsinger, Zvaifler
Ehrich 1985, 100).
Another observed
the cartilage.
is the
It has been theorized that
enzymes which
degrade the
during
proliferate
phenomenon
chondrocytes
cartilage matrix.
rheumatoid arthritis
lacunae
enlargement of the
may
produce
Chondrocytes
(Utsinger, Zvaifler
within
and
to
also tend
Ehrich 1985,
155).
One hallmark
Pannus is the ingrowth
is the
stimulus
most
likely
candidate.
cartilage
There
immature
from the
are three
synovial cells
recesses of
the
insert themselves between the
cartilage
these
is
attacked
from both
characteristics
cellular
form
is
occur
It is
unclear
multiplying
and
marginal edge of
fibers
outside and
cartilage.
and proliferate.
from
within.
classified as active pannus.
nutrition.
sequentially
or
cells and
blood
It is
unclear whether or not
the
They
also
Thus, the
Pannus showing
There is
vessels.
acellular, and it is capable of
seem
across
advancing
the
precisely
The first type
of pannus.
of pannus which appears as mature granulation
avascular and
blocking its
known types
collagen
including fibroblasts, inflammatory
dense,
tissue into the joint.
of synovial
formation.
pannus
for this, but lymphokines from helper T-cells
what
appears as
is
of chronic rheumatoid arthritis
killing
highly
also a
tissue,
A third type is
cartilage
by
these three types of pannus
independently (Fig. 11) (Utsinger, Zvaifler
and
Ehrich
1985, 155).
During
the chronic phase, blood
factor for macrophages,
which
complement
may
act as a chemotactic
then move into the synovial joints to
13
Macrophages then
phagocytose antigen complexes.
pathogenic material to
lymphocytes,
which will
in turn interact to
more antibodies which add to the aggregation of
(Utsinger, Zvaifler
Besides
lnterleukin-1
.
interleukin-2
and
lnterleukin-1
also promotes the release of
B-cell
growth
the synovium (Fig.
Not only do
factor,
in
an
lymphokines,
such as macrophage aggregation
patients
immune
response mounted against
response
is believed the primary factor in
macrophages stimulate
the
chronic
feedback
It is
of
possible
connective
that the
tissue
by
dendritic
Ehrich 1985, 156).
on
factor
helper T-cells, but
release of
and macrophage
have been found to have
damaged
(Samter
lymphocytes
cellular
which
and
during differentiation,
perpetuation of
for this
the
cartilage
et al.
may play
a role
in
is that
then stimulate macrophages and
an endless positive mutual
Ehrich 1985, 157).
during
with
the perpetuation
the routine turnover
growth and repair.
natural process
pathology.
14
an
1988, 1389). However, it
interactions involved
may be involved
some vital control mechanism
causing the
and
enzymes
perpetuation of rheumatoid arthritis
(Utsinger, Zvaifler
rheumatoid arthritis
B-cells.
Ehrich 1985, 156).
and
inflammation continues in
system
growth of
circulating in their blood. This may indicate that
perpetuating the immune
so
the
activity through the
with rheumatoid arthritis
antibodies to collagen
release
excitatory way
promote macrophage
stimulating factor (Utsinger, Zvaifler
T-cells to
destructive
12) (Utsinger, Zvaifler
macrophages act
causes
which stimulate
helper T-cells
Some
complexes
presentation, macrophages influence lymphocytes
through the release of interleukin-1
cells of
immune
produce
Ehrich 1985, 153).
and
antigen
present the
of
But possibly
may be defective,
(Utsinger, Zvaifler
and
Ehrich
1985, 157)
Rheumatoid
arthritis can not
implemented to
be cured, but treatment
reduce pain and
swelling
recommended to reduce stress on afflicted
maintaining joint mobility
may be
reduced
by
inflammatory drugs
modifiable with
azathioprine
and muscle
while
maintaining
tone (Porth 1990, 1107).
the administration of
useful
Rest is
for
Inflammation
aspirin and other nonsteroidal anti
(Porth 1990, 1108). Rheumatoid
approved.
may be
mobility.
joints. Exercise is
immunosuppressant drugs, though
is FDA
plans
If inflamed
arthritis seems
as of yet
synovial
tissue is
to be
only
unresponsive
to
drug therapies,
then surgical removal of the synovium, or synovectomy, may
be
Other
performed.
In extreme,
mobility
surgical
cases total
joint
and reduce pain
treatments include
repair of
damaged tendons.
replacements with prosthetics will
increase
(Porth 1990, 1109).
Conclusion
Myasthenia
autoimmune
healthy
gravis and rheumatoid arthritis are
diseases,
tissues
by
a
category
the immune
of ailments
system.
both
involving
Myasthenia
examples of
a mistaken attack on
gravis causes
harm
through cross reactivity between an antigen and acetylcholine receptors.
Rheumatoid
immune
complex
leukocytes
these
arthritis
and
is in
diseases,
blood
conditions
a
category
of autoimmune
which cause
complement.
has been identified
15
diseases known
lesions through the activity
Neither of the
and no cures
antigens which
as
of
trigger
have been found.
Technique
At
all
times I tried to illustrate the various cells as
alive and
inside the body,
Scanning
electron micrographs proved a valuable
cells
appear
may
My
rather
than as
distorted due to
left
artifacts
based
choices of color were
they
his textbooks.
For example, I
because that is
cartilage
illustrations.
I
stained with
My
would
few
sit
down
application
the
be
judgment,
as
while
slide preparations.
source, though
the
some
specimens.
tempered
by
to seeing the tissue in
used
the
color
for hyaline
in Frank Netter"s
appears
to represent the loose
and
because that is how it
medical
dense
appears when
eosin.
consistent
with a pad of
throughout the 12 illustrations.
drawing
lab
computer
in Adobe Illustrator
begin
and
chose not
I
paper and a pencil and make a
Once I had something that I
to trace my sketches because
to
was
drawing
utilize
they
happy
the outlines
of
the
the Adobe Streamline
drawn
were
allowed me
reasonably
roughly.
Drawing
to further refine my
and experiment with composition.
Once the
outline was completed
alias.
The
easier
to select
reason
delineated
it
by
for this
with
adjacent pixels of
changed
it
capsule
Adobe Illustrator. I
pen tool
drawings
fairly
into the
would go
objects with
with
was
rough sketches.
with, I
joint
hematoxylin and
technique
first
what color
in
look
might
by processing
light blue
chose
chose shades of pink
connective tissue of the
appear
on aesthetic
consideration of what color a student might
they
the
was
that
the outlines
color.
with
was much easier
to
tool since
The
blends
select
16
Photoshop
without
anti-
outlines without anti-alias where much
magic wand
identical
I brought it into
next
or
step
fills.
if the
they
were composed of
was
filling
If a blend
in the
and a
outlines were
areas
fill had to be
left black
until all
were complete.
In the illustration
entitled
What is
outlining in Adobe Illustrator
seemed
an antigen?,
the
forms
unnecessary (Fig. 1). For the
created a tan circle, and then added the shadows and
airbrush tool.
crevices
in the
drawn
added with
The
drawn
frame
with a
the finger tool. The
with
lines,
work of straight
with
I
the
viruses
then the highlights
were
the airbrush.
B-lymphocytes
cancer cells were
of
highlights
pollen
pollen granules were added with the
tool then smoothed and blended
pencil
were
The
were simple so
the immune response.
I
copied out of
changed
the color
of
the illustration I had
the
cell
from
magenta
to green using the color control menu, then added more texture. The
bacteria
were also extracted
The background
surface of
response was created
texture
clone
initially
from the immune
the illustration
in two steps (Fig. 2).
as a separate
document.
the texture into the background.
appear as a wall of
cloning process,
cloning
identically
reselect a
depicting
I first drew
I then
I did
utilized
not want
portion of
the immune
a small portion of the
the
rubber
stamp to
the background to
textured tiles, so I would
different
illustration.
frequently stop
the
the original texture and start
again.
A large
portion of
drawing tools,
the
yellow macrophage's
texture
was
drawn
with
the
then cloned using the same start and stop method used for
the background.
I
added
The lymphocytes
circular
response
the
core shadow with
were constructed
by
area, then adding reflected light
white with
the
highlight.
The texture
paintbrush
tool
was
adjusted
drawn
with
17
the
making
with
the
airbrush
to 50% opacity to
the
pencil
blur in a selected
a radial
airbrush
tool.
tool.
tool and a dab of
intensify
The
the
plasma cell
had
to be drawn
with
the paint brush and airbrush tool since the radial blend only
works in a perfect circle.
document
separate
The nucleus
and pasted
endoplasmic reticulum was
The bacteria
and rotated.
highlights
drawn
and
details
were
forward (Fig. 7).
fill the
of
of
Everything
the bone
by
filled
50%
with
are the same
rough
All
antibody duplicated,
drawing
resized
color, then shadows,
tools.
drawn
drawn
as a
flat
as a small
color or
blend,
except
for the
portion, then duplicated to
space.
The
neutrophils
appearing in the illustrations
were not
imported
outlines
(Figs. 9
form
the
tool and converted it to a selection.
with
pen
tool, I selectively
portion of
and
the background behind the
the
In the illustration representing
with
lines
(Fig. 10). Some fibers
were
were
The
drawn
panoramic
flat bed
by
aesthetic reasons.
a neutrophil
view of
refined pencil
moving
and
drawing
with
and
the
while
airbrush
leaving
nuclei and
a
the
painting tools.
eating through collagen, the
blue,
each one pixel wide
the cartilage undergoing destruction
drawing,
which was
distorting
right.
then scanned on a
in photoshop (Fig. 11). First the image
various areas.
Then a blend from blue to red
background from left to
The
or
then rotated to appear broken.
scanner and opened
recomposed
various
Then
fills
with
edges of the
highlights
cell still visible.
of various shades of
landscape
began as a relatively
drawn
Instead, I delineated the
10).
added purple shadows and white
arterioles were rendered with
fibers
on a
The
opacity.
the pencil tool.
with solid red
the
blend drawn
the synovial joint was relatively straight
was
which was
cell at
hand
were added with
The anatomy illustration
texture
into the
throughout the thesis
antibodies
was a radial
Then the
18
This
was
was added
surface plane was
was
purely for
to the
filled
with a
blend,
allowing it to lighten
pencil texture
for the
in the
paintbrush
"colorize"
The
utilized
in the
Out
from the
bursting
drawing. To
of all
junction
was
too
make the material appear transparent
the muscle and the
Color-Aid
shapes of the receptors
pen
tool and
I
the pannus
of
rendered.
the same
The
paper and
receptor which was
The ions streaming
and 6).
yellow
portraying the
The majority
neuron,
then scanned into
in the foreground
receptors
pair
of
were painted
Photoshop
2.0.
were then masked off with
in the middle
background
ground and
repeatedly duplicated,
the
resized and
out of the receptors were stippled
in
with
the
tool.
The
acetylcholine molecules started out as green and yellow spheres
a separate document.
lightly altering
the
in the foreground
my favorites (Figs. 4
are
The
of
neutrophil
the illustrations of my thesis work, the
illustrations, including
were all
largest diameter
explosion area.
with airbrush onto
pencil
selected the
maintain the
tool but set it to color only, and then proceeded to
pencil
neuromuscular
rotated.
So, I
the rubber stamp set to 30% opacity to clone areas
into the
these
canyon and pannus.
I wanted to
those areas.
explosion
opaque
it neared the horizon line.
as
The
component parts were
their juxtaposition.
then pasted
in,
each
Straight lines connecting the two
in
time
portions
molecules completed them.
The
orientation
cylindrical
drawing
forms for the
to show the basic form.
You must
for these two illustrations began
muscle cells
The
make a straight
(Fig. 3). I first
difficulty lay
line
attempted
When the cylinder is at an oblique angle the
to the length of the
perpendicular
the basic
making
in how the linear blend
perpendicular
19
with
a
blend
worked.
cylinder.
is difficult to
discern.
It
had drawn the
But this did
The
have been
would
cylinder as a
easier to
discern the perpendicular
horizontal,
then rotated the whole image later.
fiber
was outlined with the pen
shadow was added with the airbrush tool.
of
neuromuscular
the muscle
portion of
it
if I
not occur to me at the time.
nerve
in from the
angle
cell
was
began
tool, then filled
The inset
with yellow.
was a selection pasted
junction illustrations. The dark rings,
as one circle
A
A bands,
or
drawn in brown. Then, the
upper right
selected, duplicated and placed in a pattern, working from
front to back, gradually adjusting the opacity setting to
reduce contrast as
distance increased.
The illustration
blends in
the
all of
demonstrating
the objects, then
airbrush tool
adjacent
using
to the
image tend to
selected
reactivity
shadow and
(Fig. 5). Since the antibody
opted not to utilize the
a new one
cross
Straight
stand out as
gray line
neutral
gray
initiated
highlights
were
with
earlier.
in
with
large, I
Instead, I drew
one pixel wide, each
objects
linear
intensified
molecules were so
antibody file I had been using
various shades of
next.
was
an otherwise
drawn
full
color
artificial, so I set the airbrush tool to color only,
the pink hue of the muscle, and added it to the antibody as reflected
light.
20
Figure 1
An
antigen
immune
is any
substance which
response.
is
capable of
evoking
an
Figure 2
Depicted
above are
macrophage
the
(yellow)
cellular
interactions
engulfs some
of an
bacteria,
immune
response.
A
then activates a B-cell (pur
T-cell releases chemical mediators
ple) and a T-cell (red). The helper
larger plasma cell,
which cause the B-cell to differentiate into the much
which produces antibodies specific
for that bacteria.
Figure 3
This is an
orientation
neuromuscular
of muscle cells.
junction.
illustration designed to
show
the location
of
junction. A nerve fiber branches out to innervate
The inset is
the
a number
a magnified view of a single neuromuscular
Figure 4
The terminal
called
the
muscle
end of the nerve
lies
within an
neuromuscular synaptic cleft.
to contract
by
indentation in the
The
releasing acetylcholine,
nerve
may
muscle
stimulate
which moves across
the muscle's
the
surface.
synapse
to bind
receptor
then changes shape, allowing ions to stream in and out.
with specialized receptors on
cell,
the
The
Figure 5
Myasthenia
reactivity.
gravis
is believed to be
Antibodies
incidence, is very
similar
ceptors of muscle cells.
incapacitating
them.
caused
by
a process called cross
are produced against an antigen
in
chemical structure
These
antibodies
that, by
co
to the acetylcholine re
bind to the receptors, thereby
Figure 6
Antibodies bind to
during myasthenia gravis. Not
binding to acetylcholine, but also it
acetylcholine receptors
only does this block the
receptors
promotes their endocytosis
by
the
from
muscle cell.
Figure 7
The synovial joints
are
rheumatoid arthritis.
synovial
joint.
figures 9
and
The
12.
the most
This
cut
typically involved
away
region within
view shows
the
small
region of
the
the
body
in
major structures of
black rectangle is
the
magnified
in
Figure 8
Antibodies
are protein molecules which
bind
with an antigen as part of
the
the antibody attach to
immune response. Normally, the binding
antigen as a step towards the antigen's destruction. In rheumatoid ar
sites of
thritis,
an
forming
which
antibody binds to
the
structure of
the immune
system
then
bind to the
the
system
an unknown antigen
antibody.
interprets
synthesizes rheumatoid
altered antibodies.
together, they
are called
When
immune
A
that is capable of trans
region of
as a
foreign
factors,
the antibody is revealed
antigen.
The immune
which are antibodies
antibodies and antigens are
complexes.
an
that
bound
Figure 9
The immune
ticular
complexes of rheumatoid arthritis
cartilage.
towards the
complexes.
Phagocytic cells from the
articular cartilage after
tend to settle
blood,
called
within ar
neutrophils, move
chemically sensing these aggregated
Figure 10
Neutrophils normally attempt to engulf immune complexes before they
release their digestive enzymes. However, if the immune complexes are
the cartilage matrix, neutrophils release enzymes di
rectly onto the cartilage. These enzymes damage the collagen fibrils com
sequestered within
posing the
cartilage.
Figure 11
This is a microscopic panoramic view of the articular cartilage undergoing
destruction from rheumatoid arthritis. Neutrophils move across the cor
roded surface in search of sequestered immune complexes. The neu
trophils continue to ingest material
at
left shows a formation
which can
damage
of
until
pannus,
cartilage and
an
they burst
ingrowth
fuse joints.
open.
of
The background
the synovial membrane
Figure 12
This illustration shows some of the chemical interactions between cells
within the joint capsule. Macrophages activate helper T-cells through anti
gen presentation. The helper T-cells attract more macrophages by re
lymphokines. Lymphokines induce macrophages to release IL-1
leasing
which
,
in turn
causes
the dendritic cells to
release enzymes
that are de
The T-cells and macrophages work in concert to pro
cells. The plasma cells pro
mote the B-cells to differentiate into plasma
duce antibodies which add to the formation of new immune complexes,
structive
to
cartilage.
perpetuating the
inflammatory
response.
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of
Immunology
an
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in
immunochemistry anH
Immunofrioloqy- St. Louis: C. V. Mosby
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Bullock, Barbara L, Pearl Philbrook Rosendahl,
and
Alterations in Function 3
Dixon, Frank J., David W. Fisher,
H. P.
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PathoDhvsininnv
eds.
AHapt.tinnc
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Drachman, Daniel B., Shari De Silva, David Ramsey, Alan Pestronk. "Humoral
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Firestein, Gary S.,
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Nilsson, Linnart,
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Ross, Michael H., Edward J. Reith
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