20. Autoimmune Disorders.pptx

1. Autoimmune Disorders

2. Introduction
 When the action of the immune system is in response to self-antigens
and causes damage to one's own organs, the result is an autoimmune
disease.
 More than 40 autoimmune diseases have been identified.
 Although relatively rare, they affect about 5% of the population in the
developed world.
 About 75% of the cases of autoimmune disease selectively affect
women
 Treatments for autoimmune diseases are improving as knowledge of
the mechanisms controlling immune reactions improves
 Autoimmune diseases occur when there is a loss of self tolerance, the
immune system's ability to discriminate self from non-self

3.  In the generally accepted model by which T cells become capable of distinguishing
self from non-self, the cells acquire this ability during their passage through the
thymus.
 Any T cells that will target host cells are eliminated by thymic selection during this
period
 This step makes it unlikely that the T cell will attack its own tissue cells
 In autoimmune diseases, the loss of self-tolerance leads to the production of
antibodies or a response by sensitized T cells against a person's own tissue antigens.
Autoimmune reactions, and the diseases they cause, can be cytotoxic, immune
complex, or cell-mediated in nature
 Autoimmunity involves antibodies that attack self
 These antibodies may be made in response to an infectious agent such as a virus,
but sequence similarities between viral and self proteins may cause the antibodies
to attack self cells
 Hepatitis C virus may be responsible for autoimmune hepatitis by this mechanism

4. Cytotoxic Autoimmune Reaction
 Graves' disease and myasthenia gravis are two examples of disorders caused by
cytotoxic autoimmune reactions
 Both diseases involve antibody reactions to cell-surface antigens, although there is no
cytotoxic destruction of the cells
GRAVES' DISEASE
 Graves' disease is caused by antibodies called long-acting thyroid stimulators
 These antibodies attach to receptors on thyroid gland cells that are the normal target
cells of the thyroid stimulating hormone produced by the pituitary gland
 The result is that the thyroid gland is stimulated to produce increased amounts of
thyroid hormones and becomes greatly enlarged
 The most striking signs of the disease are goiter (a disfiguring swelling of the thyroid
gland) and markedly bulging, staring eyes

5. Myasthenia Gravis
 Myasthenia gravis is a disease in which muscles become progressively weaker
 It is caused by antibodies that coat the acetylcholine receptors at the junctions at
which nerve impulses reach the muscles
 Eventually, the muscles controlling the diaphragm and the rib cage may fail to receive
the necessary nerve signals, and respiratory arrest and death result

6. Immune Complex Autoimmune Reactions
SYSTEMIC LUPUS ERYTHEMATOSUS
 Systemic lupus erythematosus is a systemic autoimmune disease, involving immune
complex reactions, that mainly affects women
 The etiology of the disease is not completely understood, but afflicted individuals
produce antibodies directed at components of their own cells, including DNA, which
is probably released during the normal breakdown of tissues, especially the skin
 The most damaging effects of the disease result from deposits of immune complexes
in the kidney glomeruli

7. Rheumatoid Arthritis
 Crippling rheumatoid arthritis is a disease in which immune complexes of IgM, IgG,
and complement are deposited in the joints
 In fact, immune complexes called rheumatoid factors may be formed by IgM binding
to the Fc region of normal IgG
 These factors are found in 70% of individuals suffering from rheumatoid arthritis
 The chronic inflammation caused by this deposition eventually leads to severe
damage to the cartilage and bone of the joint

8. Cell Medicated Auto Immune Reactions
 Multiple sclerosis is one of the more common autoimmune diseases, affecting mostly younger
adults
 Most individuals with multiple sclerosis are whites living in northern latitudes; women are twice as
likely to have the disease
 It is a neurological disease in which T cells and macrophages attack the myelin sheath of nerves
 Symptoms range from only fatigue and weakness to, in some cases, eventual severe paralysis
 The disease progresses slowly, over many years
 New attacks that worsen the condition are often separated by long periods of remission
 There is considerable evidence of genetic susceptibility, probably not from a single gene, but from
several genes that interact
 The etiology of multiple sclerosis is unknown, but epidemiological evidence indicates that it
probably involves some infective agent or agents acquired during early adolescence
 The Epstein-Barr virus is frequently mentioned as a prime suspect
 No cure exists, but treatments with interferons and several drugs that interfere with immune
processes can significantly slow progression of symptoms

9. IDDM
 Insulin-dependent diabetes mellitus is a familiar condition caused by immunological
destruction of insulin-secreting cells of the pancreas
 T cells are clearly implicated in this disease; animals that are genetically likely to
develop diabetes fail to do so when their thymus is removed in infancy

10. Psoriasis
 The fairly common skin condition psoriasis is an autoimmune disorder characterized by
itchy-red patches of thickened skin
 As many as 25% of patients develop psoriatic arthritis
 Several topical and systemic therapies such as corticosteroids and methotrexate are
available to help control psoriasis of the skin
 Psoriasis is considered to be a Th1 disease and can be effectively treated with
immunosuppressants that target T cells and especially the cytokine, TNF-α, an
important factor in inflammation
 For psoriatic arthritis, as well as rheumatoid arthritis, the most effective treatments are
injections of monoclonal antibodies that inhibit TNF- α