Immunopathology6 Autoimmune Disorders

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Immunopathology-6Autoimmune Disorders
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Autoimmune Disorders

• Objectives
• General
• Immunologic Tolerance
• Central
• Peripheral
• Mechanisms
• Specific disorders
• SLE ( Systemic Lupus Erythematosus)
• Sjogrens Disease
• Systemic Sclerosis
• Inflammatory Myopathies
• Vascular disorders

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Autoimmune Disorders- General

• Immune reactions against self antigens
• Incidence 1-2 of SA population(increasing)
• Criteria for inclusion into autoimmune disorders
• Autoimmune reaction
• Not secondary to tissue damage
• No other simultaneous known cause
• Can be due to CMI or AMI
• Types
• Organ specific Hashimoto, MS, Type I DM
• Limited organ involvement Goodpasture's
• Generalized or Systemic SLE
• Physiological Auto- Ab are seen in
• Elderly
• Following tissue damage

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Autoimmune Disorders- Immunologic Tolerance

• Definition incapable of developing immune
  response against self Ag
• Types
• Central
• Peripheral anergy (functional inactivation),
  Regulatory T cell mediated suppression, CD4
  mediated (Fas- Fas ligand) clonal deletion, Ag
  sequestration

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Autoimmune Disorders- Mechanisms

• Role of Susceptibility Genes HLA Non HLA
  genes are involved
• Role of Infections
• up-regulate the expression of co- stimulators on
  APC or
• Molecular mimicry (microbes may express
  antigens with same amino acid sequences as
  self-antigens)
• progression and chronicity mainly by epitope
  spreading

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Autoimmune Disorders - SLE

• Chronic, relapsing remitting disease
• Organs involved skin, joints, kidney and serosal
  membranes
• Age, Ethnicity Gender women of childbearing
  age African American
• Criteria for diagnosis 4 of 11 if present
  serially or simultaneously(next slide)
• Etiology and Pathogenesis
• Cause is unknown
• Multisystem disease of autoimmune origin
• Multifactorial disorder
• fundamental defect failure of the regulatory
  mechanisms that sustain self-tolerance
• of antibodies against Nuclear and cytoplasmic
  components
• IMMUNNE FACTORS
• visceral lesions (Type III HR) Hematological
  disorders (Type II HR)
• MORPHOLOGY
• Arterioles
• Acute necrotizing Vasculitis
• Chronic fibrous thickening and luminal
  narrowing

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SLE Diagnostic Criteria
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SLE
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SLE Morphology

• MORPHOLOGY
• KIDNEY (lupus nephritis)
• 5 patterns (WHO classification)
• Class I (rare) normal by LM, IFM and EM
• Class II mesangial lupus glomerulonephritis
  (GN)
• Class III focal proliferative GN (hematuria and
  proteinuria)
• Class IV diffuse proliferative GN Most serious
  Cresentic GN (very bad prognosis) present with
  nephrotic syndrome HTN and renal insufficiency
• Class V membranous GN MC C of nephrotic
  syndromes in adults
• Mesangial immune complexes deposits earliest
  change (always present )
• IFM (Immunofluorescence Microscopy) granular
  deposits of Ig complement (unlike linear in
  Goodpasture Syndrome)
• Wire-loop lesions subendothelial deposits (poor
  prognosis)
• SKIN erythema butterfly rash (onlyin 50
  pts.) Liquefactive degeneration of the basal
  layer of the epidermis Vasculitis with fibrinoid
  necrosis IG complement deposits at
  dermoepidermal junction (Band test)

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SLE- FPGN
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SLE- DPGN
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SLE- Wire loops
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SLE- Band test
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SLE- Spleen
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SLE

• MORPHOLOGY
• JOINTS nonerosive synovitis
• CNS acute Vasculitis Or endothelial injury
  ?intimal proliferation
• CVS
• Pericarditis common
• Myocarditis resting tachycardia EKG
  abnormalities
• Endocarditis Libman Sacks -Stenosis or
  regurgitation valve thickening affects mitral
  and aortic valves vegetations (thrombi) on both
  sides of valves
• Coronary Artery Disease Young patients with
  longstanding SLE who are treated with steroids
• SPLEEN splenomegaly with Follicular hyperplasia
  perivascular fibrosis (onion-skin lesions)
• LUNGS Pleuritis and Pleural Effusions (common)
• OTHER ORGANS
• Liver (portal triaditis ) Bone Marrow
  (hematoxylin bodies) Lymph nodes(enlarged with
  hyperactive (B-cell activation)follicles

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SLE

• CLINICAL COURSE multisystem disease with Highly
  variable clinical presentation clinical course
• Typical patient Young woman with Butterfly rash
  over face Fever Joint pain but no deformity
  Pleuritic chest pain Photosensitivity.
• ANAs can be found in virtually 100 of patients.
  
• Clinical features Renal (hematuria, red cell
  casts, proteinuria and nephrotic syndrome)
  Hematologic (Anemia, thrombocytopenia) CNS
  (psychosis or convulsions) Infections
• Most common causes of death Renal failure
  Intercurrent infections CNS disease and CAD
• Variants
• Chronic Discoid Lupus Erythematosus
• Prominent Skin involvement (mainly face and scalp
  discoid lesions only 35 have ANA positive
  only involved skin shows Band test positivity
• Sub acute Cutaneous Lupus Erythematosus
  predominant skin involvement (Widespread but
  superficial nonscarring lesions) Antibodies to
  SS-A antigen HLA-DR3 genotype

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Drug induced SLE

• Drug-induced Lupus Erythematosus
• Hydralazine
• Procainamide
• Isoniazid
• D- penicillamine
• No symptoms
• Multiple organs involved but renal and CNS
  involvement very uncommon.
• Antihistone antibodies very important
• HLA-DR4 at a higher risk after hydralazine
  therapy.