MATEEN IRFANSHA

• 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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GENETIC FACTORS :-

• (+) genetic predisposition

• Strong association with HLA specificities, especially class- II genes.

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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.

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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

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Estrogens and AutoimmunityAUTOIMMUNITY

ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS

• Exposure to an environmental agent can trigger a cross-reacting immune response against some component of normal tissue.

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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.

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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

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AUTOIMMUNITY:MECHANISM:-AUTOIMMUNITY:MECHANISM:-

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.

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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

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Multiple Sclerosis

MS patients can have autoantibodies and/or self reactive T cells which are responsible for the demyelination

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Mechanism For Thyrotoxicosis

(Graves’ Disease or Exophthalmic Goiter) Is Anti-TSH Antibody

Thyrotoxicosis:-AUTOIMMUNITY

• 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)

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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

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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

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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.

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Rheumatic fever is a classic example of molecular mimicry

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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

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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

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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

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

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ClassificationCan be classified into clusters that are either

organ-specific or systemic

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Examples Of Organ Specific :-

Lungs of a patient with Goodpasture’s

Vitiligo

Hashimoto’s disease (thyroiditis)

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Examples of Systemic Autoimmunity:-• SLE :- • Sjogren’s Syndrome

• Rheumatoid arthritis

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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

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Immune RegulationA defect in any arm of the immune system can trigger autoimmunity

Complement

T cells B cells

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Complement Deficiencies

• Deficiencies in the classical complement pathway renders pts more likely to develop immune complex diseases– SLE – RA

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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

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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:-

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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).

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