Autoimmunity

1
Autoimmunity

• A breakdown of mechanisms responsible for
  tolerance. The auto-reactivity may result in
  disease.

2
Effector mechanisms of autoimmune damage

• Specific components
• Antibodies
• T cells
• Nonspecific components
• Complement
• Phagocytes (PMN and macrophages)
• NK and other cells

3
Tissues and organs involved

• Organ-specific diseases
• Damage is confined to the organ against which the
  immune response is mounted
• Non-organ-specific diseases
• Immune response against antigens which are not
  associated with the organ involved

4
Tissues and organs involved
5
Examples of autoimmune diseases
Thyroglobulin, thyroid peroxidase
Immunofluorescence (IFA), RIA, ELISA
TSH receptor
Bioassay on cell lines
Stomach, RBC
Intrinsic factor (IF)
B12 binding to IF
In diseases involving tissues, damage is also
caused by cytotoxic T cells
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Examples of autoimmune diseases
IFA
Adrenal
Pancreatic islet ß cells
Insulin-dep. diabetes
Pancreas
IFA
Goodpastures
Kidney, lung
IFA
Renal lung basement membrane
In diseases involving tissues, damage is also
caused by cytotoxic T cells
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Anti microsomal antibodies inHashimotos disease
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Graves disease
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Pernicious anemiathe mechanism
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Myasthenia gravisthe mechanism
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Pemphigus and pemphigoid
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Sjogrens syndrome
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Rheumatoid arthritis

• Characterized by the presence of rheumatoid
  factor (antibodies against IgG)

14
Systemic lupus erythematosus
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Predisposition to autoimmunitymultiple antigen
involvement
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Predisposition to autoimmunityfamilial
association
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Predisposition to autoimmunityMHC linkage
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Etiology of AI diseases
Exact etiology not known

• Sequestered antigen
• Escape of auto -reactive clones
• Cross reactive antigens
• Modification of self antigens
• Cross-reactive exogenous antigens
• Cytokine dysregulation and inappropriate MHC
  expression
• Sub-optimal suppressor function

19
Treatment of autoimmune diseases

• Symptomatic correction of metabolic consequences
• Conventional immunosuppressive agents (see
  transplantation lecture)
• Experimental treatments
• Induction of tolerance by oral administration of
  antigen
• Immunization with antigen specific receptor
  (antiidiotype immunization)

20
Experimental models of autoimmune disease

• Experimental autoallergic encephalitis (EAE)
• Experimental thyroiditis
• Adjuvant induced arthritis
• Experimental uveitis
• Others

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Experimental auto-allergic encephalitis
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Naturally occurring animal models of autoimmune
disease

• NZB (New Zealand black)
• Hemolytic anemia
• NZB/NZW, BXSB, MRL
• Systemic lupus erythematosus
• Nonobese diabetic (NOD) mice
• diabetes

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Break of tolerance due to cross reactive antigens