2. Tolerance
Tolerance of autoimmunity refers to the body's ability to recognize and tolerate its own
cells and tissues, preventing an immune response against them. Autoimmunity occurs
when the immune system mistakenly attacks healthy cells and tissues as if they were
foreign invaders.
3. The development of tolerance involves multiple
mechanisms:
• 1. Central Tolerance: This occurs during early development in the thymus and
bone marrow, where immune cells (such as T cells and B cells) are educated to
recognize and eliminate cells that could potentially initiate an autoimmune
response. Any immune cells that react strongly to self-antigens are deleted or
inactivated, preventing them from causing autoimmunity.
4. • 2. Peripheral Tolerance: This mechanism acts to control any potentially autoreactive immune cells
that have escaped central tolerance. Several mechanisms contribute to peripheral tolerance,
including regulatory T cells (Tregs) that suppress the activation of autoreactive immune cells,
activation-induced cell death, and anergy induction (in which autoantigen encounter results in
inactivation of the immune cell).
• 3. Immune Privilege: Certain tissues and organs, such as the brain and testes, have unique immune
features that restrict immune responses, reducing the likelihood of autoimmune attacks.
5. • The etiology of autoimmunity is complex and not completely understood. It is
believed to be a result of a combination of genetic, environmental, and
immunologic factors.
• Genetic factors: Certain genes are associated with an increased susceptibility to
developing autoimmune diseases. For example, certain human leukocyte antigen
(HLA) genes have been linked to autoimmune disorders. HLA molecules play a
critical role in the immune system by presenting antigens to T cells. Genetic
variations in HLA genes can lead to an aberrant immune response to self-
antigens.
6. Environmental factors: Environmental factors, such as infections, toxins, and stress, are
thought to trigger or exacerbate autoimmune diseases in individuals with a genetic
predisposition. Infections, particularly viral infections, can induce an immune response that
cross-reacts with self-antigens, leading to tissue damage. Exposure to certain toxins or
chemicals can also induce an autoimmune response by altering the normal immune tolerance
mechanisms.
Immunologic factors: Autoimmunity arises from a breakdown in the immune system's tolerance
mechanisms, which normally prevent immune cells from targeting self-antigens. Several
mechanisms contribute to the loss of self-tolerance, including defects in regulatory T cells,
abnormal activation of B cells, and breakdown of central and peripheral tolerance checkpoints.
7. Autoantigens
• Autoimmune diseases are characterized by an immune response against self-antigens, also
known as autoantigens. Autoantigens can be derived from a variety of tissues or cells,
depending on the specific autoimmune disease.
• For example, in rheumatoid arthritis, joints are targeted, and antibodies are produced
against proteins in joint tissues such as type II collagen. In type 1 diabetes, the insulin-
producing cells in the pancreas are attacked, resulting in autoantibodies against insulin or
other pancreatic cell antigens.
8. The identification and understanding of specific autoantigens
involved in various autoimmune diseases have allowed for
improved diagnosis, monitoring, and development of targeted
therapies for these disorders. However, the exact triggers and
mechanisms underlying the development of autoantigens in
autoimmune diseases are still an active area of research.
9. Classification of autoimmune disease.
• Autoimmune diseases can be classified based on various criteria, including the target
tissue or organ affected, the types of autoantibodies present, and the clinical features of
the disease. Two specific autoimmune diseases, thyrotoxicosis (specifically Graves'
disease) and myasthenia gravis, can be classified as follows:
10. Graves' disease is an autoimmune disorder primarily affecting the thyroid gland, resulting in an overactive
thyroid (hyperthyroidism). It falls into the category of organ-specific autoimmune diseases.
Classification based on autoantibodies: - Graves' disease is characterized by the presence of autoantibodies
called thyroid-stimulating immunoglobulins (TSI) or thyroid-stimulating hormone receptor (TSHR) antibodies.
These antibodies bind to the TSH receptors on thyroid cells, leading to excessive production of thyroid
hormones.
Thyrotoxicosis or Graves' disease
11. Etiology of Thyrotoxicosis or Graves'
Disease
• The exact cause of Graves' disease is not fully understood, but it is
believed to involve a combination of genetic, environmental, and
immunological factors.
• Genetic factors: There is a genetic predisposition to developing Graves'
disease, as certain human leukocyte antigen (HLA) genes and other
genetic variations are associated with an increased susceptibility.
• Environmental factors: Factors like stress, smoking, certain medications
(e.g., lithium), and viral infections have been suggested as potential
triggers for Graves' disease. However, the specific environmental factors
are not well-defined.
12. • Immunological factors: Graves' disease is an autoimmune
disorder characterized by the production of autoantibodies known
as thyroid-stimulating immunoglobulins (TSI) or thyroid-
stimulating hormone receptor (TSHR) antibodies. These
antibodies bind to the receptors on the thyroid gland, mimicking
the action of thyroid-stimulating hormone (TSH). This leads to
excessive production of thyroid hormones (triiodothyronine or T3
and thyroxine or T4) and hyperthyroidism.
13. Mechanism:
• Although the precise trigger for the production of TSI antibodies is unclear, it is
believed that a loss of immune tolerance occurs, leading to an aberrant immune
response against thyroid tissue. The TSI antibodies bind to the TSH receptors,
stimulating the release of thyroid hormones, which disrupts the normal negative
feedback loop of the hypothalamic-pituitary-thyroid axis and results in the
overproduction of thyroid hormones.
14. Treatment
• The goal of treatment for Graves' disease is to reduce thyroid
hormone levels, manage symptoms, and prevent long-term
complications. Treatment options may include:
• 1. Anti-thyroid medications: Drugs like methimazole and
propylthiouracil (PTU) inhibit the production of thyroid hormones.
They are used to achieve a euthyroid state (normal thyroid
hormone levels). These medications may be used as the sole
treatment or as a preparatory step before other interventions.
15. 2. Radioactive iodine therapy: Radioactive iodine, in the form of a capsule or liquid, is
ingested and selectively absorbed by the overactive thyroid cells. The radiation
effectively destroys the hyperactive tissue, leading to a decrease in thyroid hormone
production. This treatment often results in eventual hypothyroidism, which may require
lifelong thyroid hormone replacement.
3. Beta-blockers: Medications such as propranolol can help alleviate symptoms
associated with hyperthyroidism, such as rapid heart rate, tremors, and anxiety. These
drugs do not target the underlying cause of Graves' disease but provide symptomatic
relief.
16. Myasthenia Gravis
• Myasthenia gravis is an autoimmune disease that affects the neuromuscular
junction, leading to muscle weakness and fatigue. It is classified as a
neuromuscular autoimmune disease.
• Classification based on autoantibodies: - Myasthenia gravis is associated with the
presence of autoantibodies called acetylcholine receptor (AChR) antibodies. These
antibodies bind to the acetylcholine receptors on muscle cells, impairing
neuromuscular transmission and causing muscle weakness.
17. Classification based on clinical features:
• Myasthenia gravis can also be classified based on the pattern of muscle weakness. There are
various types, including ocular myasthenia gravis (limited to the eyes), generalized myasthenia
gravis (involving muscles throughout the body), and congenital myasthenic syndromes (rare
genetic forms).
• It is worth noting that autoimmune diseases can have overlapping features, and an individual may
develop multiple autoimmune conditions simultaneously or sequentially. Proper diagnosis and
classification of autoimmune diseases are essential for appropriate treatment and management
strategies.
18. Etiology of Myasthenia Gravis:
• The exact cause of Myasthenia Gravis (MG) is not fully understood, but it is thought to
involve a combination of genetic, immunological, and environmental factors.
• Genetic factors: There is evidence of a genetic predisposition to MG, as certain human
leukocyte antigen (HLA) genes and other gene variations are associated with an increased
risk of developing the condition. However, the inheritance pattern is complex and not well-
defined.
19. • Immunological factors: MG is an autoimmune disorder where the body's immune
system mistakenly targets and attacks the neuromuscular junction (NMJ). Most cases
of MG are caused by autoantibodies called acetylcholine receptor (AChR) antibodies.
These antibodies interfere with the normal functioning of acetylcholine receptors on
muscle cells, leading to impaired neuromuscular transmission and muscle weakness.
20. Mechanism
• The main mechanism of MG involves the disruption of neuromuscular communication.
Acetylcholine is a neurotransmitter that transmits nerve impulses across the NMJ,
allowing muscles to contract. In MG, autoantibodies bind to and block the acetylcholine
receptors on muscle cells or accelerate their degradation. This interference leads to a
reduction in the number of available receptors, subsequent decrease in the effectiveness
of neuromuscular transmission, and muscle weakness.
21. Treatment
• The treatment of MG aims to improve muscle strength, relieve symptoms, and prevent
complications. The treatment approach may vary depending on the severity of the
disease, age, general health, and specific needs of the individual. Common treatment
options include:
• 1. Acetylcholinesterase inhibitors: Medications like pyridostigmine enhance acetylcholine
levels at the NMJ by inhibiting the enzyme that breaks down acetylcholine. This improves
neuromuscular transmission and temporarily relieves muscle weakness.
22. 2. Immunosuppressive drugs: Medications that suppress the abnormal immune response in MG are often
prescribed, especially in more severe cases or when initial treatments are inadequate. These may include
corticosteroids (e.g., prednisone), immunosuppressants (e.g., azathioprine, methotrexate), or newer biologic
therapies (e.g., rituximab).
3. Thymectomy: Surgical removal of the thymus gland (thymectomy) can be an effective treatment for MG,
particularly in individuals with thymoma or those under 60 years of age. Thymectomy helps reduce the
production of autoantibodies and may lead to long-term remission.
4. Plasmapheresis: In this procedure, the individual's blood is filtered to remove autoantibodies and other
immune components responsible for MG. Plasmapheresis is often used for short-term symptom relief in severe
cases or as a bridge therapy before other treatments take effect. improvement of symptoms.
