Organ-specific autoimmune diseases affect a single organ through immune responses directed against antigens in that organ. Examples include Hashimoto's thyroiditis, where antibodies attack thyroid proteins and cause hypothyroidism, and myasthenia gravis, where antibodies block acetylcholine receptors and cause muscle weakness. Type 1 diabetes results from an immune attack on insulin-producing pancreatic beta cells that leads to insulin deficiency. Graves' disease occurs when antibodies activate thyroid stimulating hormone receptors, causing overproduction of thyroid hormones. Addison's disease involves the destruction of adrenal glands by an autoimmune response.

1. ORGAN-SPECIFIC
AUTOIMMUNE
DISEASES
SUBMITTED BY,
SRUTHI JOSY
19PZOO9683

2. CLASSIFICATION OF
AUTOIMMUNE DISORDERS
 Autoimmune diseases can be broadly divided into systemic and
organ-specific or localised autoimmune disorders, depending on
whether they affect a single organ or multiple systems in the
body.
An organ-specific disease is one in which an immune response
is directed toward antigens in a single organ. Examples
are Addison disease, in which autoantibodies attack the adrenal
cortex, and myasthenia gravis, in which they attack
neuromuscular cells.
In systemic diseases the immune system attacks self antigens in
several organs. Systemic lupus erythematosus, for example, is
characterized by inflammation of the skin, joints, and kidneys,
among other organs.

4. ORGAN SPECIFIC OR
LOCALIZED AUTOIMMUNE
DISEASE
In an organ-specific autoimmune disease, the immune response
is usually directed to a target antigen unique to a single organ or
gland, so that the manifestations are largely limited to that organ.
The cells of the target organs may be damaged directly by
humoral or cell mediated effector mechanisms.
 Alternatively, anti-self antibodies may overstimulate or block the
normal function of the target organ.

5. HASHIMOTO’S
THYROIDITIS
In Hashimoto’s thyroiditis, an individual produces autoantibodies and
sensitized TH1 cells specific for thyroid antigens. Th is disease is
much more common in women, often striking in middle-age.
Antibodies are formed to a number of thyroid proteins, including
thyroglobulin and thyroid peroxidase, both of which are involved in
the uptake of iodine.
 Binding of the auto-antibodies to these proteins interferes with
iodine uptake, leading to decreased thyroid function and
hypothyroidism (decreased production of thyroid hormones).
The resulting delayed-type hypersensitivity (DTH) response is
characterized by an intense infiltration of the thyroid gland by
lymphocytes, macrophages, and plasma cells, which form
lymphocytic follicles and germinal centers.
 The ensuing inflammatory response causes a goiter, or visible
enlargement of the thyroid gland, a physiological response to
hypothyroidism.

7. TYPE 1 DIABETES
MELLITUS
Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes,
seen mostly in youth under the age of 14 and is less common than
Type 2, or non-insulin dépendent diabetes mellitus.
 T1DM is caused by an autoimmune attack against insulin-
producing cells (beta cells) scattered throughout the pancreas,
which results in decreased production of insulin and consequently
increased levels of blood glucose.
 The attack begins with cytotoxic T lymphocyte (CTL) infiltration
and activation of macrophages, frequently referred to as insulitis,
followed by cytokine release and the production of autoantibodies,
which leads to a cell-mediated DTH response.
The subsequent beta-cell destruction is thought to be mediated by
cytokines released during the DTH response and by lytic enzymes
released from the activated macrophages.
 Autoantibodies specific for beta cells may contribute to cell
destruction by facilitating either antibody-mediated complement
lysis or antibody-dependent cell-mediated cytotoxicity (ADCC).

8. Th e abnormalities in glucose metabolism associated with T1DM
result in serious metabolic problems that include ketoacidosis
(accumulation of ketone, a breakdown product from fat) and
increased urine production.
The late stages of the disease are oft en characterized by
atherosclerotic vascular lesions (which cause gangrene of the
extremities due to impeded vascular flow), renal failure, and
blindness.
If untreated, death can result. Th e most common therapy for
T1DM is daily administration of insulin. Although this is helpful,
sporadic doses are not the same as metabolically regulated,
continuous, and controlled release of the hormone.
Unfortunately, diabetes can remain undetected for many years,
allowing irreparable loss of pancreatic tissue to occur before
treatment begins.

9. Photomicrographs of an islet of Langerhans in
(a) pancreas from a normal mouse and
(b) Pancreas from a mouse with a disease resembling insulin dependent
diabetes mellitus
(b)(a)

10. MYASTHENIA GRAVIS
Myasthenia gravis is the classic example of an autoimmune
disease mediated by blocking antibodies.
A patient with this disease produces auto-antibodies that bind
the acetylcholine receptors (AchRs) on the motor end plates of
muscles, blocking the normal binding of acetylcholine and
inducing complement-mediated lysis of the cells. The result is a
progressive weakening of the skeletal muscles.
Ultimately, the antibodies cause the destruction of the cells
bearing the receptors. Th e early signs of this disease include
drooping eyelids and inability to retract the corners of the mouth.
Without treatment, progressive weakening of the muscles can
lead to severe impairment of eating as well as problems with
movement.
However, with appropriate treatment, this disease can be
managed quite well and afflicted individuals can lead a normal life.
Treatments are aimed at increasing acetylcholine levels (e.g., using
cholinesterase inhibitors), decreasing antibody production (using
corticosteroids or other immunosuppressants), and/or removing
antibodies (using plasmapheresis).

12. Myasthenia gravis and impaired muscle contraction. (a) Normal
release of the neurotransmitter acetylcholine stimulates muscle
contraction. (b) In myasthenia gravis, autoantibodies block the
receptors for acetylcholine (AChr) on muscle cells, resulting in
paralysis.

13. GRAVES DISEASE
Graves’ disease is an example where binding of
autoantibodies to cell surface receptors results in activation of
the cell.
 In Graves’ disease, autoantibodies to thyroid stimulating
hormone (TSH) receptors bind to TSH receptors on thyroid
and lead to excessive production of thyroid hormones.
This may cause conflicting symptoms because it may
stimulate the thyroid to make too much thyroid hormone or
block thyroid hormone production entirely, making diagnosis
more difficult.
 Signs and symptoms of Graves disease include heat
intolerance, rapid and irregular heartbeat, weight
loss, goiter (a swollen thyroid gland, protruding under the
skin of the throat and exophthalmia (bulging eyes) often
referred to as Graves ophthalmopathy.

14. Exophthalmia, or Graves
ophthalmopathy, is a sign of
Graves disease
Goiter, a hypertrophy of the
thyroid, is a symptom of Graves
disease and Hashimoto thyroiditis.

15. ADDISON DISEASE
Destruction of the adrenal glands (the glands lying above the
kidneys that produce glucocorticoids, mineralocorticoids, and
sex steroids) is the cause of Addison disease, also called primary
adrenal insufficiency (PAI).
Today, up to 80% of Addison disease cases are diagnosed as
autoimmune Addison disease (AAD), which is caused by an
autoimmune response to adrenal tissues disrupting adrenal
function. Disruption of adrenal function causes impaired
metabolic processes that require normal steroid hormone levels,
causing signs and symptoms throughout the body.
There is evidence that both humoral and CD4 TH1-driven CD8
T-cell–mediated immune mechanisms are directed at the adrenal
cortex in AAD. There is also evidence that the autoimmune
response is associated with autoimmune destruction of other
endocrine glands as well, such as the pancreas and thyroid,
conditions collectively referred to as autoimmune polyendocrine
syndromes (APS).

16. In up to 80% of patients with AAD, antibodies are produced to
three enzymes involved in steroid synthesis: 21-hydroxylase
(21-OH), 17α-hydroxylase, and cholesterol side-chain–cleaving
enzyme.
The most common autoantibody found in AAD is to 21-OH,
and antibodies to any of the key enzymes for steroid production
are diagnostic for AAD.
The adrenal cortex cells are targeted, destroyed, and replaced
with fibrous tissue by immune-mediated inflammation. In some
patients, at least 90% of the adrenal cortex is destroyed before
symptoms become diagnostic.
Symptoms of AAD include weakness, nausea, decreased
appetite, weight
loss, hyperpigmentation, hyperkalemia (elevated blood
potassium levels), hyponatremia (decreased blood sodium
levels), hypoglycemia (decreased levels of blood
sugar), hypotension (decreased blood
pressure), anemia, lymphocytosis (decreased levels of white
blood cells), and fatigue.
Under extreme stress, such as surgery, accidental trauma, or
infection, patients with AAD may experience an adrenal crisis
that causes the patient to vomit, experience abdominal pain,
back or leg cramps, and even severe hypotension leading to

17. Hyperpigmentation is a sign of
Addison disease.

18. AUTOIMMUNE HEMOLYTIC
ANEMIA
In autoimmune hemolytic anemia, auto antibodies to self-
RBCs are formed. The autoantibodies bind to antigens on
RBCs and lead to the lysis of RBCs. Most drugs are not
immunogenic by themselves, but they may act as
haptens.
The drug forms a complex with protein antigens on RBCs.
The drug-RBC antigen complex induces the immune
system to produce antibodies. The antibodies formed
against the drug-RBC antigen complex bind to the RBC
and activate the complement cascade, resulting in RBC
lysis.

19. PERNICIOUS ANEMIA
Pernicious anemia is a chronic disease resulting from the non-
absorption of vitamin B12, which is essential for the
development of RBCs.
Pernicious anemia, is most common in late adult life. The
basic abnormality of the disease is severe atrophic gastritis,
wherein there is extreme deficiency of all the gastric secretions,
including intrinsic factor.
The gastric lesion probably develops due to an autoimmune
attack on gastric cells.

20. The autoantibodies to intrinsic factor may interfere with the
absorption of vitamin B12 by the following mechanisms:
i. In pernicious anemia, the intrinsic factor autoantibodies in
gastric juice may bind to intrinsic factor and block the binding of
vitamin B12 to intrinsic factor
ii. The autoantibody to intrinsic factor may bind to intrinsic
factor-B12 complex and interferes with the absorption of the
complex. Consequently, the absorption of vitamin B12 is
interfered, resulting in decreased production of RBCs.
Pernicious anemia patients are treated by regular vitamin
B12 injections.

21. GOODPASTURE’S
SYNDROME
Autoantibodies to certain antigens on the membrane of kidney
glomeruli and lung alveoli are formed in a condition called Good
pasture’s syndrome.
Binding of autoantibodies to the membrane antigens in lung and
kidney leads to complement activation, resulting in inflammatory
reactions in lung and kidney.
Consequently, the kidneys are damaged and the patient also
suffers from pulmonary hemorrhage (i.e. bleeding from lungs).

22. THANKYOU