OBJECTIVES
•DEFINITION •TOLERANCE •FACTORS OF AUTOIMMUNITY •MECHANISMS OF AUTOIMMUNITY •CLASSIFICATION OF AUTOIMMUNEDISEASES

TOLERANCE
DEFINITION:
•IT is specific immunologic unresponsiveness

•TYPES:
•T-CELL TOLERANCE •B-CELL TOLERANCE •CENTRAL TOLERANCE •PERIPHERAL TOLERANCE

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.Autoimmunity  Basically means immunity to self  A condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue.

 Because of this autoimmune diseases are generally classified as complex diseases as there is not a single “pinpoint-able” gene .Genes and Autoimmunity  The concept that a single gene mutation leads to a single autoimmune disease is the EXCEPTION not the rule.

Many autoimmune diseases are associated with certain HLA types and with gender .

Hormones  Females are much more likely to develop autoimmune illness  Rise in hormones associated with pregnancy supports the idea Hypothesis: estrogen response elements (EREs) in several genes .

Estrogens and Autoimmunity .

777 .780 (2001) .Sex differences in autoimmunity Nature Immunology 2.

ENVIRONMENTAL FACTORS Environmental factors elicit autoimmune diseases by: 1-molecular mimic theory 2-tissue injury releases intracellular antigens that elicit immune response .

CID. WA.4).2. hormones      External triggering factors infections UV drugs chemicals (including food) stress . CVID. C1.Factors influencing autoimmune disease      Internal triggering factors genotype / HLA cytokines apoptosis genes ID (IgA.

•MOLECULAR MIMICRY •ALTERATION OF NORMAL PROTEINS •RELEASE OF SEQUESTERED ANTIGENS •EPITOPE SPREADING .

Rheumatic fever is a classic example of molecular mimicry .

. any organ . Autoimmunity can affect ANY organ/organ system in the human body Autoimmune Uveitis Sjogren’s Syndrome Multiple Sclerosis Pemphigus Goodpasture’s Syndrome Diabetes Addison’s Disease Rheumatic Fever Autoimmune Hepatitis Autoimmune Oophoritis Rheumatoid Arthritis Ulcerative Colitis Autoimmune hemolytic Anemia . .Pick an organ.

Autoimmunity Classification Can be classified into clusters that are either organ-specific or systemic .

Multiple Sclerosis MS patients can have autoantibodies and/or self reactive T cells which are responsible for the demyelination of white matter of brain .

Glutamic acid decarboxylase .DIABETES : Auto destructive T cells destroy the islets cells of pancreas •The main antigen against which t cells attack is directed is the islet cell enzyme .

Diabetes .

anti-TSHR) In Graves’ disease. they bind and activate the TSH receptor) (agonist) (compare this to the Hashimoto’s thyroiditis..e. previous slide) .Graves’ disease (anti-thyroid stimulating hormone Normal receptor. the antibodies do not destroy the thyroid but act as if they are TSH (i.

Myasthenia gravis (anti-acetylcholine receptors) In myasthenia gravis the antibodies bind the acetylcholine receptor and cause it to be cleared from the surface of the muscle .

Autoimmune hemolytic anemia .

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nucleolar proteins etc 2 drugs procainamide and hydralazine causes SLE SLE Individuals with HLA-DR2 and HLA_DR3 are predisposed to SLE Treatment involves NSAIDS.Aspirin.histones.Autoantibodies are formed Against DNA.Corticosteri ods .

Examples of Systemic Autoimmunity SLE .

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macrophages Rheumatoid arthritis Treatment is NSAIDS.corticosteroids Clinical finding is inflammation of joints of hands and feet .Autoantibodies are formed against igG Synovial memb infiltrated With t cells.plasma cells.immunosuppressive drugs.

GOODPASTEURS SYNDROME .

Auto antibodies are formed against collagen in basement membranes of kidneys and lungs Clinical findings Hematurea Proteinurea Pulmonary hemorrhage Goodpasteurs syndrome Cytotoxic antibodies activate complement c5a released neurtophils enzymes destroy lung and kidney tissue Treatment include Plasma exchange to remove antibodies Immunosuppresive drugs .

REFERENCES •LEVINSON MEDICAL MICROBIOLOGY AND IMMUNOLOGY •ROBBINS AND KUMAR •WWW.COM FOR PICTURES .GOOGLE.

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