Normally, the immune system does not attack the self. However, there is a large group of autoimmune diseases in which the immune system does attack self-cellsThe attack can be directed either against a very specific tissue or to a large no. of tissuesOnce started, autoimmune diseases are hard to stop
During Hashimoto's thyroiditis, self-reactive CD4+ T lymphocytes recruit B cells and CD8+ T cells into the thyroid. Disease progression leads to the death of thyroid cells and hypothyroidism. Both autoantibodies and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion. b | In Graves' disease, activated CD4+ T cells induce B cells to secrete thyroid-stimulating immunoglobulins (TSI) against the thyroid-stimulating hormone receptor (TSHR), resulting in unrestrained thyroid hormone production and hyperthyroidism.
It is due to adrenocortical damage & hence insufficient secretion of adrenal hormones.Tissue damage is caused by auto Ab against zonaglomerulosa cells of adrenal cortex.Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialized world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase .This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.
The main source of energy for all cells and especially for brain cells is glucose.
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 1Outline:
Auto or self antigens Are antigens that presents in ones own cells Are altered by the action of bacteria, viruses, chemicalsor other drugs Auto antibodies Altered cell (Auto Ag) - elicits the productions ofAntibody
Autoimmunity is defined as the presence of immuneresponse of auto Ab against self Ag. It can be a humoral or cell mediated immuneresponse against the constitutents of the body’s owntissues.What is autoimmunity?
Autoimmunity is the failure of an organism inrecognizing its own constituent parts as non self,which allows an immune response against its owncells and tissues. Any disease that results from suchan aberrant immune response is termed anautoimmune disease.Autoimmune disease
1. Sequestered or Hidden antigens Ag in the secluded places - are not accessible to theimmune 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 isabrogated.Causes of autoimmunediseases
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 & Renalglomeruli shares similar epiotes.5. Loss of Immunoregulation Loss of Self tolerance - caused by over activity orlowered activity of T and B- cellsCauses of autoimmunediseases..
Clinical disorder due to destructions of bloodcomponents. Auto Ab are formed against one’sown RBCs, Platelets or Leucocytes. E.g. Haemolytic anaemia Thrombocytopenia Leucopenia1. Haemolytic autoimmunediseases
A particular organ is affected due to auto Abs.For example: Thyroiditis Multiple sclerosis Myasthenia gravis Type I Diabetes Mellitus Graves’ Disease2. Localised autoimmune diseases orOrgan specific autoimmune diseases
Immune complexes accumulate in many tissues andcause inflammation and damage Affects many organs or the whole body E.g. Systemic lupus erythematosus Rheumatoid arthritis Rheumatic fever3. Systemic autoimmune disease ornon-specific autoimmune disease
Graves disease is an autoimmune disease where thethyroid is overactive, producing an excessiveamount of thyroid hormones (a serious metabolicimbalance known as hyperthyroidism andthyrotoxicosis). This is caused by thyroid autoantibodies thatactivate the TSH-receptor, thereby stimulatingthyroid hormone synthesis and secretion, andthyroid 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 thyroidhormones T3 and T4 may also be produced.) These antibodies (TSHR-Ab) bind to the TSH-Rs,which are located on the cells that produce thyroidhormone in the thyroid gland (follicular cells), andchronically stimulate them, resulting in anabnormally high production of T3 and T4.Graves’ Disease…
This causes thestimulation of Thyroidgland to secrete moreTH (Hyperthyroidism)resulting inExophthalmus , bulgingeyes & Goitre.Graves’ Disease…Davidson’s book
Hashimotos thyroiditis is a condition caused byinflammation of the thyroid gland. It is the most common thyroid disease in the U.S. Is characterized by the destruction of thyroid cells byvarious cell- and antibody-mediated immuneprocesses. Caused by auto Ab of IgG & IgM type against theconstituents of thyroid glandHashimoto’s thyroiditis
Abs are specifically formed for thyroid perioxidase &thyroglobulin.Abs interact with the enzymeDevelopment of inflammation in the thyroid glandThyroid gland is destroyedPatient ultimately rendered hypothyroid (too little thyroidhormone)Hashimoto’s thyroiditis pathogenesis
Comparison of Hashimoto’sthyroiditis & Graves DiseaseNature Reviews Immunology 2
Characterised byGoitre, enlargedthyroid gland,deficiency of TH(Thyroxin)flipper.diff.org/hashimoto’s thryoiditis
Addisons disease, or primary adrenocorticalinsufficiency, is an autoimmune diseasecharacterized by the presence of autoantibodiesdirected predominantly against 21-hydroxylase, akey regulator of mineralocorticoid andglucocorticoid synthesis.Addison’s Disease
The myriad clinical manifestations of Addisonsdisease, including muscle weakness andfatigue, hypotension and hyponatremia, and loss ofaxillary and pubic hair in women, are the result ofcortisol, aldosterone and sex hormonedeficiencies, respectively.Addison’s Disease
MG is a chronic autoimmune neuromuscular diseasethat affects the myoneural junction that ischaracterized by varying degrees of weakness of theskeletal (voluntary) muscles of the body. Classified as a “B cell” Disease Autoantibodies against nicotinic acetylcholinereceptorsMyasthenia Gravis
Myasthenia gravis is caused by a defect in thetransmission of nerve impulses to muscles. It occurs when normal communication between thenerve and muscle is interrupted at theneuromuscular junction - the place where nerve cellsconnect with the muscles they control. Normally when impulses travel down the nerve, thenerve endings release a neurotransmitter substance,acetylcholine.Myasthenia Gravis
Acetylcholine travels through the neuromuscularjunction and binds to acetylcholine receptors whichare activated and generate a muscle contraction. In myasthenia gravis, auto Abs block, alter, ordestroy the receptors for acetylcholine at theneuromuscular junction which prevents the musclecontraction from occurring.Myasthenia Gravis
Insulin dependent diabetes mellitus (type 1) is an inflammatoryautoimmune disease of the pancreas, resulting in a lack ofinsulin. Insulin is produced in the pancreas by beta cells of the islets ofLangerhans. Insulin is necessary for glucose to get into cells andbe used for energy production. After eating, the glucose level inblood rises, which leads to insulin being released from thepancreas. In a person with type 1 diabetes mellitus, the beta cells ofLangerhans are damaged by autoimmuneinflammation, leading to an insufficiency of insulin. Theglucose level in blood rises and cells do not have enoughenergy for metabolism.Diabete Mellitus Type 1
Type 2 diabetes (non-insulin-dependent diabetesmellitus) Insulin concentrations are mostly increasedbut peripheral tissues are resistant to insulin (insulinresistance). Beta cells are not able increase secretionof insulin to overcome this resistance. Type 2diabetes usually develops after 40 years of age inoverweight people, lately in obese adolescents.Type 2 Diabetes Mellitus