Download - Auto immunity- by mateen irfansha
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MATEEN IRFANSHA
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• Basically means immunity to self antigens.
• A condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue.
•Most important steps in production of autoimmune disease: activation of self reactive CD4+T cells i.e failure of immune tolerance . So… Most are antibody mediated.
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AUTOIMMUNITY
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GENETIC FACTORS :-
• (+) genetic predisposition
• Strong association with HLA specificities, especially class- II genes.
AUTOIMMUNITY
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Examples:-• Class I MHC-related :-
- ankylosing spondylitis & Reiter’s syndrome.
- more common in men.
• Class II MHC-related :-
- RA , Grave’s disease & SLE.
- more common in women.
AUTOIMMUNITY
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HORMONAL FACTORSHORMONAL FACTORS
• Approximately 90% occur in women
• Estrogen can alter the B-cell repertoire and enhance formation of antibody to DNA
AUTOIMMUNITY
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Estrogens and AutoimmunityAUTOIMMUNITY
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ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS
• Exposure to an environmental agent can trigger a cross-reacting immune response against some component of normal tissue.
AUTOIMMUNITY
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• Example:
• Pathogens:-
S. pyogenes ( rheumatic fever)• Drugs:- - Procainamide , Phenytoin & etc -Drugs induced lupus mimics SLE.• Toxins:- -toxic oil syndrome. -mecury. -lead. -cow milk (casein). -soya.
AUTOIMMUNITY
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• Defects in clonal deletion mechanismsDefects in clonal deletion mechanisms
• Polyclonal lymphocyte activationPolyclonal lymphocyte activation
• Molecular mimicryMolecular mimicry
• Release of sequestered antigensRelease of sequestered antigens
• Co-stimulatorsCo-stimulators
AUTOIMMUNITY
AUTOIMMUNITY:MECHANISM:-AUTOIMMUNITY:MECHANISM:-
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Defects in clonal deletion mechanismsDefects in clonal deletion mechanisms
• Thymic defects that lead to proliferation of self-reactive T cells.
• Failure of central tolerance.
• Examples:-
-Diabetes,
-Multiple Sclerosis,
-Thyrotoxicosis &
-Myasthenia Gravis.
AUTOIMMUNITY
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AUTOIMMUNITY
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Diabetes
Disease in which the body does not produce or properly use insulin
“ T cell” Disease
T cells attack and destroy pancreatic beta cells
AUTOIMMUNITY
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Multiple Sclerosis
MS patients can have autoantibodies and/or self reactive T cells which are responsible for the demyelination
AUTOIMMUNITY
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Mechanism For Thyrotoxicosis
(Graves’ Disease or Exophthalmic Goiter) Is Anti-TSH Antibody
Thyrotoxicosis:-AUTOIMMUNITY
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• Alternative names :- - Chronic lymphocytic thyroiditis - Autoimmune thyroiditis • Female to male ratio of :- 12:1• T3,T4 (decrease) and TSH (increase) serum levels. • Effector mechanisms :-• Autoantibodies specific for - Thyroglobulin - Thyroid peroxidase • CD8 T cells
HASHIMOTO'S DISEASE (THYROIDITIS)
AUTOIMMUNITY
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Mechanism:-Disease marked by progressive weakness and lossof muscle control Classified as a “B cell” DiseaseAutoantibodies against nicotinic acetylcholinereceptors
Myasthenia Gravis
AUTOIMMUNITY
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Polyclonal lymphocyte activation
Examples:-
• Microorganism-derived mitogens stimulate lymphocytes
-Microbial products (e.g. LPS) act as superantigens activate a large pool of T and B cells.
. S.L.E
AUTOIMMUNITY
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SLEAUTOIMMUNITY
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Molecular mimicryMolecular mimicry
• Microbial antigens with similar structure to self-antigens activate auto-reactive T cells.
• Cross-reactivity-induced immune response.
• Example: M protein of S. pyogenes and myosin of cardiac muscle.
AUTOIMMUNITY
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Rheumatic fever is a classic example of molecular mimicry
AUTOIMMUNITY
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Release of sequestered antigensRelease of sequestered antigens
• Immunologically privileged sites (brain, ant. eye chamber, ovary, placenta, testis, pregnant uterus) not exposed to immune system
• Damage release of antigens elicit immune response
AUTOIMMUNITY
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• Release of sequestered Ag.
• Smoking can trigger Goodpasture’s syndrome.
• Alveolar basement membrane normally not exposed to immune system.
Lungs of a patient with Goodpasture’s
Goodpasture’s syndrome
AUTOIMMUNITY
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AUTOIMMUNITY: MechanismsAUTOIMMUNITY: Mechanisms
Defects in the regulation of THDefects in the regulation of TH11 and and THTH22 cells cells
• Impaired T suppressor cell Impaired T suppressor cell immunoregulationimmunoregulation
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Pick an organ, any organ . . .Autoimmunity can affect ANY organ/organ system in the human body
Pemphigus
Multiple Sclerosis
Sjogren’s Syndrome
Rheumatic Fever
Autoimmune Hepatitis
Ulcerative Colitis
Goodpasture’s Syndrome
Diabetes
Autoimmune Uveitis
Autoimmune hemolytic Anemia
Addison’s Disease
Rheumatoid Arthritis
Autoimmune Oophoritis
AUTOIMMUNITY
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ClassificationCan be classified into clusters that are either
organ-specific or systemic
AUTOIMMUNITY
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Examples Of Organ Specific :-
Lungs of a patient with Goodpasture’s
Vitiligo
Hashimoto’s disease (thyroiditis)
AUTOIMMUNITY
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Examples of Systemic Autoimmunity:-• SLE :- • Sjogren’s Syndrome
• Rheumatoid arthritis
AUTOIMMUNITY
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Microbial infections associated with
autoimmune diseases:-
Microbe Autoimmune disease
BACTERIA Streptococcus pyogenes Campylobacter jejuni Escherichia coli Chlamydia trachomatis Shigella sp. Yersinia enterocolitica Borrelia burgdorferi
Rheumatic feverGuillain-Barre syndromePrimary biliary cirrhosisReiter’s syndromeReiter’s syndromeGrave’s diseaseLyme arthritis
VIRUSES Hepatitis B virus Hepatitis C virus Measles virus Cytomegalovirus
Multiple sclerosisMixed cryoglobulinemiaAllergic encephalitisScleroderma
AUTOIMMUNITY
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Immune RegulationA defect in any arm of the immune system can trigger autoimmunity
Complement
T cells B cells
AUTOIMMUNITY
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Complement Deficiencies
• Deficiencies in the classical complement pathway renders pts more likely to develop immune complex diseases– SLE – RA
AUTOIMMUNITY
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Symptoms :-
• Initial diagnosis may be missed in patients as diseases present with general symptoms.– Fever, muscle ache, fatigue, joint pain
• Disease specific manifests:-– SLE – rash– Sjogren’s – dry mouth, dry eyes
AUTOIMMUNITY
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• General tests:-
– C Reactive Protein .– Autoantibody titers (anti DNA, anti phospholipids,etc) .– Presence of Rheumatoid Factor. • Disease specific tests :
– Neurological exam – MS.– Fasting glucose – Diabetes.
Diagnosis:-
AUTOIMMUNITY
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Treatment Options :- • Anti-inflammatory drugs:- - NSAIDS, Corticosteroids . • Immunosuppressant drugs:- - Methotrexate. • Radiation. • Plasmapheresis . • Cell Blocking Reagents:- - aCD20 (Rituxan). - aCD3 (Teplizumab) . • Cytokine Blocking Reagents:- - TNF (Humira, Enbrel).
AUTOIMMUNITY
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THANK U……