Autoimmune Disorders

Disorders of immunity-II Autoimmune disorders

Dr. Mehzabin Ahmed

AUTOIMMUNE DISORDERS

 Immune

reaction against self antigens

 Auto antibodies are produced against ones own (self) tissues  Autoimmunity can involve a single organ or multiple systems

Examples of single organ or cell type autoimmunity Hashimoto's thyroiditis Graves disease Autoimmune hemolytic anemia Autoimmune atrophic gastritis of Pernicious anemia Autoimmune thrombocytopenia Autoimmune orchitis Insulin-dependent diabetes mellitus Myaesthenia gravis Goodpasture syndrome

Examples of systemic/ multi organ involvement  Systemic

lupus erythematosus,

 Rheumatoid arthritis,  Sjogren syndrome,  Reiter syndrome.

Immunological tolerance A

state of incapability of developing an immune response

to a specific antigen  Self-tolerance refers to lack of responsiveness to self antigens (an individual's own antigens).  Autoreactive T cells are thus controlled by the body's own mechanisms.  Failure of these mechanisms results in autoimmunity

Factors influencing autoimmunity Genetic:  Familial clustering of several human autoimmune diseases is seen e.g. SLE, autoimmune thyroiditis.  Several autoimmune diseases are linked to HLA, class II antigens.   Microbial Agents:  Cross reaction of the microbial epitopes with self antigens.  Tissue necrosis causes up-regulation of the T cell activation.  Super antigens can activate a large pool of T and B cells, some of these may be autoreactive.

Systemic Lupus Erythematosus  Autoimmune

disorder,

 Acute or insidious in onset  Becomes a chronic remitting, relapsing disease  Lesions mainly in skin, joints, kidney, and serosal membranes.  Autoantibodies directed against nuclear antigens like DNA, histones, nucleolar and non-histones bound to RNA.

Factors influencing SLE Genetic:  Genetic predisposition is linked to HLA - DQ. Environmental:  Drugs - hydrallazine, procainamide, D-pencillamine UV light.  Hormones : Females> male in reproductive years. Immunological:  Helper T cell induced production of IgG against self antigens.

Lesions in SLE Kidney: Glomerulonephritis- deposition of DNA and then the anti-DNA antibody. 

 Skin: Butterfly pattern of malar rash. Also seen on trunks and limbs and increase on exposure to light.  Joints: Non-erosive synovitis and little deformity  CNS: Non-inflammatory occlusion of small vessels because of damage by antibodies.  Heart: Endocarditis  Spleen, Lungs, liver, may be involved.

Sjogren Syndrome: Sicca Syndrome Can occur singly or in association with other autoimmune disorders like, Rheumatoid arthritis, SLE, thyroiditis.  It is characterized by dry conjunctiva - keratoconjunctivitis sicca dry mouth - xerostomia.  Autoimmune destruction of lacrimal and salivary glands.  HLA - B, DR, DQ. 

Causes •

Immunological

•

Environmental: Virus: Ebstein Barr Virus (EBV) HIV- I and HTLV - 1

Lesions •

Salivary glands: Dry mouth → dysphagia & loss of taste sensation. Cracks and fissures- at the angles of the mouth.

2.

Lacrimal glands: Dry eyes → blurring of vision, Burning sensation & itching Thick secretions in the conjunctival sac.

Enlargement of the Parotid gland

Systemic Sclerosis - Scleroderma Excessive fibrosis throughout the body. Two categories: 1) Diffuse - widespread, rapid, viscera involved early. 2) Localized - limited area, viscera involved later. Causes: 1) Immunological: abnormal activation of immune system. 2) Vascular abnormalities: Intimal fibrosis

Clinical features of Females > males - 3:1. Skin : diffuse, sclerotic atrophy Alimentary: Progressive atrophy & fibrosis rubber hose inflexibility, Esophageal dysmotility Musculoskeletal - Synovial inflammation and fibrosis Kidneys - Intimal thickening causing hypertension Lungs - Fibrosis, pulmonary hypertension Heart - Fibrosis of myocardium, pericarditis CREST syndrome - limited sclerosis Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia

early gangrenous necrosis from vasospasm with the Raynaud phenomenon

Tightening of the skin over the fingers- making them appear claw like

Tight shiny skin Cheilosis at the angles of the mouth is due to riboflavin deficiency due to malabsorption

Inflammatory Myopathies 3 distinct disorders are seen Dermatomyositis Polymyositis Inclusion body myositis Causes : Immunological: CD 8 + T cells, MCH – I, Anti nuclear antibodies are found

Dermatomyositis Skin as well as the muscles are involved. Children or adults Skin - Lilac rash of upper eyelids with periorbital edema Grotton lesion - Knuckles, elbows, knees have red patches. Muscles: Weakness of proximal muscles first,thus fine movements are affected last. Bilateral symmetry Slow onset Dysphagia can occur Heart and lungs can be involved

Polymyositis Adults No skin involvement Proximal muscle involvement Heart and lung can be involved

Inclusion Body myositis Adults over 50 years Distal muscle involvement Extensors of knee, flexor of wrist and fingers Asymmetrical involvement

Rheumatoid Arthritis Chronic systemic inflammatory disorders of joints. Synovitis causes destruction of articular cartilage Factors involved in pathogenesis: Genetic susceptibility: Association with HLA - DR Microbial agents: EBV, Borrelia, myoplasma Autoimmunity: EBV and collagen type 2- crossing over of immune response , eg. joint cartilage.

Clinical features of RA General symptoms of malaise, fatigue, pain Involvement of small joints of hands and feet Joints - Swelling, pain, early morning stiffness Deformities occur because of destruction of tendons, ligaments and joint capsules. Loss of range of movements and decreased stability

Ulnar deviation of the wrist Destruction of articular cartilage by the inflammatory pannus

Boutonniere & the swan neck deformity

Myaesthenia Gravis Immune mediated loss of acetylcholine receptors. Most commonly seen in women when it arises before 40 years. But after 40 years both sexes are equally affected. Pathogenesis: Anti - acetylcholine receptors antibodies Thymic hyperplasia is seen in 65% Thymoma in 15%

Clinical features of Myaesthenia Gravis Weakness begins in extra ocular muscles Drooping of eyelids & double vision (diplopia).