Lec 03: Autoimmune DIseases Flashcards
What are the three requirements for a disease to be classified as autoimmunity?
- presence of an immune reaction specific for
some self-antigen or self-tissue - evidence that such a reaction is of primarily pathogenic in significance
- absence of another well-defined cause of
disease
What is immunological tolerance?
unresponsiveness to an antigen as a result of
exposure of lymphocytes to that antigen
What are the two types of self-tolerance?
central and peripheral tolerance
What is the difference between central and peripheral tolerance?
central - deletion of self-reactive T & B cell clones
during maturation in the thymus or bone
marrow
peripheral - self-reactive T cells that escape thymic
deletion are silenced in the periphery
What mechanisms are utilized in central tolerance?
o Negative selection or Deletion
o Receptor Editing
o Development of regulatory T cells
What mechanisms are used in peripheral tolerance?
o Anergy (Prolonged or irreversible functional
inactivation of lymphocytes)
o Suppression by Regulatory T cells
o Deletion by activation-induced cell death
o Antigen Sequestration
What conditions may result in failure of peripheral tolerance?
- Breakdown of T cell anergy
- Failure of activation-induced cell death
- Failure of T cell-mediated suppression
- Molecular mimicry
- Polyclonal lymphocyte activation
- Release of sequestered antigens
- Exposure of cryptic self and epitope spreading
(T/F) The inheritance of susceptibility genes is the only factor that may produce autoimmunity.
F
What diseases are associated with polymorphisms in PTPN22?
Rheumatoid Arthritis, type 1 DM, and other autoimmune diseases (most frequently implicated gene in autoimmunity)
Which disease is associated with polymorphisms in NOD-2?
Crohn’s disease
What are the general features of an autoimmune disease?
o tends to be progressive
o clinical and pathologic manifestations are determined by the nature of the underlying immune response
o different autoimmune diseases show substantial
clinical, pathologic, and serologic overlaps
What are the general characteristics of SLE?
o multi-system autoimmune disease
o presence of antinuclear antibodies
o characterized principally by injury to the skin, joints, kidney, and serosal membranes
What are antinuclear antibodies?
autoantibodies that react with protein or nucleic
acid in nucleus
What method is commonly used to detect antinuclear antibodies?
indirect immunofluorescence
What are the 4 categories of antinuclear antibodies?
- Antibodies to DNA
- Antibodies to histones
- Antibodies to nonhistone proteins bound to RNA
- Antibodies to nucleolar antigens
What is the substrate of dsDNA antibodies?
Crithidia (a protozoa with
a kinetoplast of pure dsDNA, without histone)
What are the screening tests used in detecting SLE?
ANA - 99% sensitivity
Anti dsDNA - high specificity, sensitivity 70%
Anti- Sm - most specific antibody test, 30-40% sensitivity
Anti- SSA - present in 15% of patients with SLE and Sjogren’s syndrome
Anti- histone - Drug- induced lupus ANA antibodies
What are the patterns of kidney injury in SLE?
minimal, mesangial, focal proliferative,
diffuse proliferative, membranous
How are the affected blood vessels of those with SLE described?
“Onion skinning”
What are the ACR Criteria for SLE Dx?
at least 4/11 of the ff.:
serositis, oral ulcers, arthritis, photosensitivity, blood disorder, renal disorder, antinuclear antibody, immunologic disorder, neurologic disorder, malar rash, discoid rash
What drugs are used to manage SLE?
Hydroxychloroquine, NSAIDs, steroids
(T/F) kidney transplant is a definitive treatment for lupus nephritis
F
What is Sjogren’s syndrome?
Immunologic destruction of lacrimal and salivary
glands
What are the two forms of systemic sclerosis?
o Diffuse scleroderma
o Limited scleroderma/ CREST Syndrome
