autoimmune diseases autoimmune diseases martin liška

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  • Slide 1
  • AUTOIMMUNE DISEASES AUTOIMMUNE DISEASES Martin Lika
  • Slide 2
  • Autoimmune disease Results from a failure of self-tolerance Immunological tolerance is specific unresponsiveness to an antigen All individuals are tolerant of their own (self) antigens
  • Slide 3
  • Autoimmunity is defined as an immune response against self antigens The principal factors in the development of autoimmunity are the inheritance of susceptibility genes and environmental triggers, such as infections Most autoimmune diseases are polygenic and are asssociated wih multiple gene loci, the most important of which are the MHC genes Infections may activate self-reactive lymphocytes, thereby triggering the development of autoimmune diseases
  • Slide 4
  • AUTOIMMUNE PATOLOGICAL RESPONSE- ETIOLOGY the diseases are chronic and usually irreversible incidence: 5%-7% of population, higher frequencies in women, increases with age factors contributing to autoimmunity: - internal (HLA association, polymorphism of cytokine genes, defect in genes regulating apoptosis, polymorphism in genes for TCR and H immunoglobulin chains, association with immunodeficiency, hormonal factors) - internal (HLA association, polymorphism of cytokine genes, defect in genes regulating apoptosis, polymorphism in genes for TCR and H immunoglobulin chains, association with immunodeficiency, hormonal factors) - external (infection, stress by activation of neuroendocrinal axis and hormonal dysbalance, drug and ionization through modification of autoantigens) - external (infection, stress by activation of neuroendocrinal axis and hormonal dysbalance, drug and ionization through modification of autoantigens)
  • Slide 5
  • Type II hypersensitivity reaction IgM and IgG Ab promote the phagocytosis of cells which they bind, induce inflammation by complement and Fc receptor- mediated leukocyte recruitment, and may interfere with the functions of cells by binding to essential molecules and receptors. Graves disease, Pernicious anemia, Myasthenia gravis, Acute rheumatic fever, Goodpastures syndrome, Pemphigus vulgaris, Autoimmune hemolytic anemia or thrombocytopenic purpura
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  • Type III hypersensitivity reaction Ab may bind to circulating antigens to form immune complexes, which deposit in vessels and cause tissue injury. Injury is due mainly to leukocyte recruitment and inflammation. Systemic lupus erythematosus, Polyarteritis nodosa, Poststreptococcal glomerulonephritis
  • Slide 7
  • Type IV hypersensitivity reaction T cell- mediated diseases are caused by Th1-mediated delayed-type hypersensitivity reactions or Th17- mediated inflammatory reactions, or by killing of host cells by CD8+ CTLs (cytotoxic lymphocytes). Diabetes mellitus (insulin-dependent), Rheumatoid arthritis, Multiple sclerosis, Inflammatory bowel disease
  • Slide 8
  • CLINICAL CATEGORIES systemic - affect many organs and tissue - affect many organs and tissue organoleptic - affect predominantly one organ accompanied by affection of other organs (inflammatory bowel diseases, coeliac disease, AI hepatitis, pulmonary fibrosis) - affect predominantly one organ accompanied by affection of other organs (inflammatory bowel diseases, coeliac disease, AI hepatitis, pulmonary fibrosis) organ specific - affect one organ or group of organs connected with development or function - affect one organ or group of organs connected with development or function
  • Slide 9
  • EXAMPLES OF SYSTEMIC AUTOIMMUNE DISEASES examples autoantibodies
  • Slide 10
  • SYSTEMIC AUTOIMMUNE DISEASES Systemic lupus erythematosus Rheumathoid arthritis Sjgrens syndrome Dermatopolymyositis Systemic sclerosis Mixed connective tissue disease Vasculitis
  • Slide 11
  • SYSTEMIC LUPUS ERYTHEMATOSUS chronic, inflammatory, multiorgan disorder autoantibodies react with nuclear material and attack cell function, immune complexes with dsDNA deposit in the tissue general symptoms: include malaise, fever, weight loss multiple tissue are involved including the skin, mucosa, kidney, joints, brain and cardiovascular system characteristic features: butterfly rash, renal involvement, CNS manifestation, pulmonary fibrosis
  • Slide 12
  • DIAGNOSTIC TESTS a elevated ESR (erythrocyte sedimentation rate), low CRP, trombocytopenia, leucopenia, hemolytic anemia, decreased levels of complement compounds (C4, C3), elevated serum Ig levels, immune complexes in serum
  • Slide 13
  • AUTOANTIBODIES Autoantibodies: ANA, dsDNA (double- stranded), ENA (SS-A/Ro, SS-B/La), Sm, against histones, phospholipids
  • Slide 14
  • RHEUMATOID ARTHRITIS chronic, inflammatory disease with systemic involvement characterized by an inflammatory joint lesion in the synovial membrane, destruction of the cartilage and bone, results in the joint deformation clinical features: arthritis, fever, fatigue, weakness, weight loss systemic features: vasculitis, pericarditis, uveitis, nodules under skin, intersticial pulmonary fibrosis diagnostic tests: elevated C- reactive protein and ESR, elevated serum gammaglobulin levels and ESR, elevated serum gammaglobulin levels - autoantibodies against IgG = rheumatoid factor - autoantibodies against IgG = rheumatoid factor (RF), a-CCP (cyclic citrulline peptid), ANA (RF), a-CCP (cyclic citrulline peptid), ANA - X-rays of hands and legs- show a periarticular - X-rays of hands and legs- show a periarticular porosis, marginal erosion porosis, marginal erosion
  • Slide 15
  • SJGRENS SYNDROME chronic inflammatory disease affecting exocrine glands the primary targets are the lacrimal and salivary gland duct epithelium general features: malaise, weakness, fever primary syndrome - features: dry eyes and dry mouth, swollen salivary glands, dryness of the nose, larynx, bronchi and vaginal mucosa, involvement kidney, central and periferal nervous system, arthritis secondary syndrome is associated with others AI diseases (SLE, RA, sclerodermia, polymyositis, primary biliary cirhosis,AI thyroiditis) autoantibodies against ENA (SS-A, SS-B), ANA, RF ANA, RF The Schirmer test - measures the production of tears of tears
  • Slide 16
  • Heliotrope rash is a violaceous eruption on the upper eyelids, often with swelling a connective-tissue disease related to polymyositis (PM) that is characterized by inflammation of the muscles and the skin. Gottron's sign is an erythematous, scaly eruption occurring in symmetric fashion over the MCP and interphalangeal joints Dermatopolymyositis
  • Slide 17
  • Dermatopolymyositis Elevated creatine phosphokinase (CPK) muscle biopsy (a mixed B- and T-cell perivascular inflammatory infiltrate, perifascicular muscle fiber atrophy) EMG (electromyogram) autoantibodies - ENA (Jo-1)
  • Slide 18
  • Systemic sclerosis sclerosis in the skin or other organs Diffuse scleroderma (progressive systemic sclerosis) is the most severe form, involves skin, will generally cause internal organ damage (specifically the lungs and gastrointestinal tract) involves skin, will generally cause internal organ damage (specifically the lungs and gastrointestinal tract) The limited form is much milder The limited form is often referred to as CREST syndrome (CREST is an acronym for the five main features: Calcinosis, Raynaud's syndrome, Esophageal dysmotility, Sclerodactyly, Telangiectasia
  • Slide 19
  • Immunological findings ANA, ENA - anti-Scl-70 (fluorescence of nucleolus), anti-centromers
  • Slide 20
  • Mixed connective tissue disease combines features of polymyositis, systemic lupus erythematosus, scleroderma, and dermatomyositis (overlap syndrome) Causes : joint pain/swelling, malaise, Raynaud phenomenon, muscle inflammation and sclerodactyly (thickening of the skin of the pads of the fingers) Distinguishing laboratory characteristics: a positive, speckled anti-nuclear antibody (ANA) and anti-U1-RNP antibody (ENA) a positive, speckled anti-nuclear antibody (ANA) and anti-U1-RNP antibody (ENA)
  • Slide 21
  • Vasculitis characterized by inflammatory destruction of vessels leading to thrombosis and aneurysms of vessels leading to thrombosis and aneurysms proliferation of the intimal part of blood-vessel wall and fibrinoid necrosis affect mostly lung, kidneys, skin diagnostic tests: elevated ESR, CRP, leucocytosis, biopsy of affected organ (necrosis, granulomas), angiography
  • Slide 22
  • Vasculitis p- ANCA (myeloperoxidase) positivity (Polyarteritis nodosa, Churg- Strauss, Microscopic polyarteritis nodosa) c- ANCA (serin proteinase) positive (Wegener granulomatosis, Churg- Strauss syndrome) granulomatosis, Churg- Strauss syndrome)
  • Slide 23
  • Classification Large vessel vasculitis (Takayasu arteritis, Giant cell (temporal) arteritis) Medium vessel vasculitis (Polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease) Small vessel vasculitis (Churg-Strauss arteritis, Microscopic polyarteritis, Henoch- Schnlein purpura) Symptoms: fatigue, weakness, fever, arthralgias, abdominal pain, hypertension, renal insufficiency, and neurologic dysfunction
  • Slide 24
  • EXAMPLES OF ORGANOLEPTIC AUTOIMMUNE DISEASES diseases autoantibodies
  • Slide 25
  • ORGANOLEPTIC AUTOIMMUNE DISEASES Ulcerative colitis Crohns disease Autoimmune hepatitis Primary biliary cirhosis Pulmonary fibrosis