AUTOIMMUNE DISEASES

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AUTOIMMUNE DISEASES

• Dr. Imran Mirza
• Department of Pathology Laboratory Medicine
• University of Alberta

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Learning Objectives

• To understand the principles of tolerance
• To describe the mechanisms of autoimmunity
• To list a few autoimmune diseases and their
  clinical features
• To describe the methods of treatment for
  autoimmune diseases

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The Major Histocompatibility Complexaka. Human
Leukocyte Antigens

• Proteins that are products of cluster of genes on
  chromosome 6
• Multiple variants of these genes exist (alleles)
• Class I MHC molecules are present on the surface
  of virtually all cells
• Class II MHC molecules are normally limited to
  cells of immune system
• All cells that carry Class II antigens also carry
  Class I molecules

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MHC (HLA) Disease Association

• A variety of diseases have been found to be
  associated with certain HLA alleles.
• The diseases that show association with the HLA
  locus can be broadly grouped into the following
  categories
• Inflammatory diseases, including ankylosing
  spondylitis and several postinfectious
  arthropathies, all associated with HLA-B27
• Inherited errors of metabolism, such as
  21-hydroxylase deficiency (HLA-BW47) and
  hereditary hemochromatosis (HLA-A)
• Autoimmune diseases, including autoimmune
  endocrinopathies, associated mainly with alleles
  at the DR locus.

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Tolerance

• Central Tolerance Deletion of self reactive T
  and B lymphocytes during their maturation in the
  central nervous system
• Peripheral Tolerance Self-reactive T cells can
  be made tolerant through
• Induction of anergy
• Activation induced cell death
• Peripheral suppression through regulatory T cells

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T Cell Signaling for Activation
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Pathogenesis of Autoimmune Diseases
Genes
Environment
Immune Regulation
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Pathogenesis of Autoimmune Diseases

• Alteration of the patients own (self) antigens
  that causes them to become antigenic and provoke
  an immune reaction
• Formation of cross-reacting antibodies against
  foreign antigens that also attack the patients
  own antigens (molecular mimicry)
• Defective regulation of the immune response by
  regulator T lymphocyte

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Pathogenesis of Autoimmune Diseases
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Autoimmune Diseases

• Examples
• Lupus erythematosus (systematic manifestations in
  various organs)
• Rheumatoid fever (inflammation in heart joints)
• Glomerulonephritis (inflammation in renal
  glomeruli)
• Autoimmune blood diseases (anemia, leukopenia, or
  thrombocytopenia)
• Thyroiditis (hypothyroidism)
• Diffuse toxic goiter (hyperthyroidism)

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Systemic Lupus Erythematosus
http//www.lupus.org/education/sympt.html
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Systemic Lupus Erythematosus
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LE Cell in Lupus Erythematosus
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Histology of Rheumatoid Arthritis
Normal Joint Lining (synovium)
Joint lining with inflammatory reaction
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Suppression of the Immune Response

• Reasons for Suppression
• Autoimmune diseases
• To prevent rejection of transplanted organs
• To prevent the Rh hemolytic disease in newborn
  infants

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Suppression of the Immune Response

• Methods of Suppression
• Radiation
• Immunosuppressive drugs that impede cell division
  or cell function (e.g. cyclosporine)
• Adrenal corticosteroid hormones (steroids)
• Gamma globulin preparations containing potent
  antibodies (e.g. Rh immune globulin)

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Questions??