AUTOIMMUNE DISORDERS
By: Safana Sadiq
What is autoimmunity Causes of autoimmune disorders Classification of autoimmune disorders Examples of autoimmune disorders:
Graves’ disease Hashimoto’s thyroiditis Addison’s disease Myasthenia gravis Diabetes mellitus type 1
Outline:
Auto or self antigens
Are antigens that presents in ones own cells Are altered by the action of bacteria, viruses,
chemicals or other drugs
Auto antibodies Altered cell (Auto Ag) - elicits the productions of
Antibody
Autoimmunity is defined as the presence of
immune response of auto Ab against self Ag.
It can be a humoral or cell mediated immune response against the constitutents of the body’s own tissues.
What is autoimmunity?
Autoimmunity is the failure of an organism in
recognizing its own constituent parts as non self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease.
Autoimmune disease
1. Sequestered or Hidden antigens Ag in the secluded places - are not accessible
to the immune system. E.g. Lens Ag, Sperm Ag, etc.2. Neo antigens Altered or Modified Antigens – by physical
(irradiation), chemical (drugs) or microbial agents ( intracellular viruses)
3. Cessation of Tolerance It may result when tolerance to the self-Ag is
abrogated.
Causes of autoimmune diseases
4. Cross reacting Antigens A foreign Ag which resembles self a 2nd Ag Many species share organ specific Ags. E.g. Ag of Human brain & Ag of sheep brain,
Streptococcal M protein & Heart muscles, Nephritogenic strains of Streptococci Ags & Renal glomeruli shares similar epiotes.
5. Loss of Immunoregulation Loss of Self tolerance - caused by over activity
or lowered activity of T and B- cells
Causes of autoimmune diseases..
Broadly classified into 3 groups
1. Haemolytic autoimmune diseases
2. Localised autoimmune diseases
3. Systemic autoimmune diseases
Classification of autoimmune
disorders
Clinical disorder due to destructions of blood
components. Auto Ab are formed against one’s own RBCs, Platelets or Leucocytes.
E.g. Haemolytic anaemia Thrombocytopenia Leucopenia
1. Haemolytic autoimmune diseases
A particular organ is affected due to auto Abs. For example:
Thyroiditis Multiple sclerosis Myasthenia gravis Type I Diabetes Mellitus Graves’ Disease
2. Localised autoimmune diseases or
Organ specific autoimmune diseases
Immune complexes accumulate in many
tissues and cause inflammation and damage Affects many organs or the whole body E.g.
Systemic lupus erythematosus Rheumatoid arthritis Rheumatic fever
3. Systemic autoimmune disease or non-specific autoimmune disease
GRAVES’ 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 thyroid autoantibodies that activate the TSH-receptor, thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter).
Graves’ Disease
The body produces antibodies to the TSH-Rs
(Thyroid Stimulating Hormone Receptors). *(Antibodies to thyroglobulin and to the thyroid
hormones T3 and T4 may also be produced.)
These antibodies (TSHR-Ab) bind to the TSH-Rs, which are located on the cells that produce thyroid hormone in the thyroid gland (follicular cells), and chronically stimulate them, resulting in an abnormally high production of T3 and T4.
Graves’ Disease…
This causes the
stimulation of Thyroid gland to secrete more TH (Hyperthyroidism) resulting in Exophthalmus , bulging eyes & Goitre.
Graves’ Disease…
Davidson’s book
HASHIMOTO’S THYROIDITIS
Hashimoto's thyroiditis is a condition caused
by inflammation of the thyroid gland. It is the most common thyroid disease in the
U.S. Is characterized by the destruction of thyroid
cells by various cell- and antibody-mediated immune processes.
Caused by auto Ab of IgG & IgM type against the constituents of thyroid gland
Hashimoto’s thyroiditis
Abs are specifically formed for thyroid perioxidase &
thyroglobulin.
Abs interact with the enzyme
Development of inflammation in the thyroid gland
Thyroid gland is destroyed
Patient ultimately rendered hypothyroid (too little thyroid hormone)
Hashimoto’s thyroiditis pathogenesis
Comparison of Hashimoto’s thyroiditis & Graves Disease
Nature Reviews Immunology 2
Characterised by
Goitre, enlarged thyroid gland, deficiency of TH (Thyroxin)
flipper.diff.org/hashimoto’s thryoiditis
ADDISON’S DISEASE
Addison's disease, or primary adrenocortical
insufficiency, is an autoimmune disease characterized by the presence of autoantibodies directed predominantly against 21-hydroxylase, a key regulator of mineralocorticoid and glucocorticoid synthesis.
Addison’s Disease
The myriad clinical manifestations of Addison's
disease, including muscle weakness and fatigue, hypotension and hyponatremia, and loss of axillary and pubic hair in women, are the result of cortisol, aldosterone and sex hormone deficiencies, respectively.
Addison’s Disease
MYASTHENIA
GRAVIS
MG is a chronic autoimmune neuromuscular
disease that affects the myoneural junction that is characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body.
Classified as a “B cell” Disease Autoantibodies against nicotinic acetylcholine
receptors
Myasthenia Gravis
Myasthenia gravis is caused by a defect in the
transmission of nerve impulses to muscles.
It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction - the place where nerve cells connect with the muscles they control.
Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance, acetylcholine.
Myasthenia Gravis
Acetylcholine travels through the
neuromuscular junction and binds to acetylcholine receptors which are activated and generate a muscle contraction.
In myasthenia gravis, auto Abs block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction which prevents the muscle contraction from occurring.
Myasthenia Gravis
Diplopia (double vision)
Ptosis (drooping of eyelids)
Current Mdeical Diagnosis & Treatment 2007, 46th Ed.
DIABETES
MELLITUS TYPE 1
Insulin dependent diabetes mellitus (type 1) is an inflammatory
autoimmune disease of the pancreas, resulting in a lack of insulin.
Insulin is produced in the pancreas by beta cells of the islets of Langerhans. Insulin is necessary for glucose to get into cells and be used for energy production. After eating, the glucose level in blood rises, which leads to insulin being released from the pancreas.
In a person with type 1 diabetes mellitus, the beta cells of Langerhans are damaged by autoimmune inflammation, leading to an insufficiency of insulin. The glucose level in blood rises and cells do not have enough energy for metabolism.
Diabete Mellitus Type 1
Type 2 diabetes (non-insulin-dependent
diabetes mellitus) Insulin concentrations are mostly increased but peripheral tissues are resistant to insulin (insulin resistance). Beta cells are not able increase secretion of insulin to overcome this resistance. Type 2 diabetes usually develops after 40 years of age in overweight people, lately in obese adolescents.
Type 2 Diabetes Mellitus
Immunobiology 6th Ed.
Nature Reviews Immunology 2, p.195-204
(March 2002) Dr.T.V.Rao’s lecture note on Autoimmunity Robbins Basic Pathology, 8th Edition www.wikipedia.org/addison’s disease www.wikipedia.org/myasthenia gravis Burmester GR, Pezzuto A. Colour Atlas of
Immunology . 2003. www.diseases_john_hopkins_medical_institute/t
ype1_diabetes_mellitus
www.slideshare.net/autoimmunedisorders
References:
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