autoimmune diseases
TRANSCRIPT
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AUTOIMMUNE DISEASES
PRESENTED BY- HASNAHANA CHETIA
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DEFINITION
Autoimmune diseases are diseases that arise from an overactive immune response of the body against substances and tissues normally present in the body. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to certain organs or involve a particular tissue in different places. The treatment of autoimmune diseases is typically with immunosuppression—a medication which decreases the immune response.
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SYMPTOMS
The symptoms of autoimmune disease vary depending on the disease as well as the person's immune system. Common symptoms include:
Anxiety or depression Blood sugar changes Digestive or gastrointestinal problems Dizziness Elevated fever and high body temperature Extreme sensitivity to cold in the hands and feet Fatigue Infertility Inflammation Irritability
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Low or high blood pressure Malaise Weakness and stiffness in muscles and
joints Weight Changes And depending on the type of
autoimmune disease: Destruction of an organ or tissue Increase in the size of an organ or tissue
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Autoimmune diseases can be classified into 2 broad categories-
1. Organ-specific 2. Systemic
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ORGAN-SPECIFIC AUTOIMMUNE DISEASES
In this type, the immune response is directed to a target antigen unique to a single organ or gland. The cells of the organ may be damaged directly by humoural or cell-mediated effector mechanisms. Alternatively, the antibodies may overstimulate or block the normal functions of the target organ.
Eg- Hashimoto’s thyroiditis
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Organ-specific Auto-immune diseases are mediated by-
A. Direct Cellular Damage where lymphocytes or antibodies bind to cell-membrane antigens, causing cellular lysis and/or an inflammatory response in the organ as a result of which the damaged cellular structure is replaced by connective tissue (scar tissue) and the function of the organ declines.
Diseases caused by this are-
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HASHIMOTO’S THYROIDITIS
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes due to production of auto-antibodies and sensitized Th1 cells for thyroid antigens. It was the first disease to be recognized as an autoimmune disease and was discovered by Dr. Hashimoto Hakaru.
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AUTOIMMUNE ANEMIAS
An individual with this disease makes auto-antibody to RBC antigens, triggering complement-mediated lysis or opsonization and phagocytosis of RBCs. These are of 3 types-
1. Pernicious anemia 2. Autoimmune hemolytic anemia 3. Drug-induced hemolytic anemia
These are usually detected by Coomb’s test where RBCs are incubated with anti-human IgG serum.
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GOODPASTURE’S SYNDROME
Here auto-antibodies specific for certain basement membrane antigens bind to the basement membranes of kidney glomeruli and alveoli of lungs. Subsequent complement activation leads to cellular damage and an ensuing inflammatory response. Death is ensued within several months of onset of symptoms.
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Fig. Lung diagnosed with Goodpasture’s syndrome
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INSULIN-DEPENDENT DIABETES MELLITUS Diabetes mellitus type 1 (Type 1 diabetes,
IDDM, or, formerly, juvenile diabetes) is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst),polyphagia (increased hunger), and weight loss.
Type 1 diabetes is fatal unless treated with insulin.
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B. Stimulating or Blocking Auto-antibodies where antibodies act as agonists, binding to hormone receptors in lieu of the normal ligand and stimulating inappropriate activity. This usually leads to an over-production of mediators or an increase in cell growth.
Conversely, antibodies may act as antagonists, binding hormone receptors but blocking receptor function. This generally causes impaired secretion of mediators and gradual atrophy of the affected organ.
Diseases caused by this are-
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GRAVE’S DISEASE
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones (a serious metabolic imbalance known as hyperthyroidism and thyrotoxicosis. This is caused by autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR), thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter. The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms.
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FIG. GRAVE’S DISEASE PATIENT
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MYASTHENIA GRAVIS
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle
weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter
acetylcholine. Myasthenia is treated medically with cholinesterase inhibitors or
immunosuppressants, and, in selected cases, thymectomy.
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FIG. SHOWING THYMOMA AND PARIAL PTOSIS CHARACTERISTIC OF MYASTHENIA GRAVIS
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SYSTEMIC AUTOIMMUNE DISEASES
In this type, the immune response is not directed to a target antigen unique to a single organ or gland, rather it is directed to any different organs, tissues, and cells of the body.
Eg- Systemic lupus erythematosus
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SYSTEMIC LUPUS ERYTHEMATOSUS Systemic lupus erythematosus is
a systemic autoimmune disease that can affect any part of the body. Affected individuals produce auto-antibodies to a vast array of tissue antigens, such as DNA,histones, RBCs,platelets, leukocytes etc often through excessive complement activation. The treatment of SLE involves preventing flares and reducing their severity and duration when they occur & treatment can include corticosteroids and anti-malarial drugs.
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Fig. A baby suffering from SLE
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MULTIPLE SCLEROSIS
Multiple sclerosis is aninflammatory disease in which the fatty myelin sheaths around the axon of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. Affected people’s cerebrospinal fluid contains activated T-cells that infiltrate brain tissue and cause characteristic inflammatory lesions, destroying myelin leading to neurological dysfunctions.
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RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium (synovitis) secondary to hyperplasia of synovial cells, excess synovial fluid, and the development of pannus in the synovium. The pathology of the disease process often leads to the destruction of articular cartilage and
ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and sclera, and also nodular lesions, most common insubcutaneous tissue. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is considered a systemic autoimmune disease.
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Fig. Hand of a person infected with RA
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GENDER DIFFERENCES IN AUTOIMMUNITY
Women are more susceptible to Autoimmune diseases than men. This is because it has been deduced that women produce higher titer of antibodies than men and so, in general, mount more vigorous immune responses. Women generally tend to have higher levels of CD4+ T cells and significantly higher levels of serum IgG.
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TREATMENT
Current therapies for autoimmune diseases include-
1.Immunosuppressive drugs 2.Thymectomy 3.Plasmapherisis 4.Vaccination with T cells specific for an auto-antigen 5.Usage of Synthetic Blocking Peptides 6.Usage of Monoclonal Antibodies
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REFERENCES
Immunology by Kuby Wikipedia www.ncbi.nlm.nih.gov www.medconnect.in
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