Autoimmunity. A breakdown of mechanisms responsible for tolerance. The auto-reactivity may result in disease. Contents:. General introduction Immunologic pathogenesis involved in autoimmune diseases Proposed mechanisms for induction of autoimmunity Treatment of autoimmune diseases.
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A breakdown of mechanisms responsible for tolerance.
The auto-reactivity may result in disease.
An acquired immune reactivity against self antigens.
Autoimmunity can be found in normal persons.
Tissue damage caused by autoimmune responses.
The autoantibodies and autoreactive T cells against self antigens exist in all the individuals with autoimmune disease.
Immunologic pathogenesis involved in typical autoimmune diseases
Insulin-dependent diabetes mellitus
Characterized by the presence of rheumatoid factor (antibodies against IgG)
Staining for immune complexes
in lupus nephritis (left) and Anti-renal
basement membrane antibody
In Goodpasture's nephritis (right)
Immunofluorescent detection of
antinuclear antibody in the
serum of an SLE patient
Proposed mechanisms for induction of autoimmunity
Any tissue antigens that are sequestered from the circulation, and therefore not seen by the developing T cells in the thymus, will not induce self-tolerance.
Exposure of mature T cells to such normally sequestered antigens at a later time might result in their activation.
Myelin basic protein (MBP)
Sperm, lens protein, heart-muscle antigens
Abnormal expression of Fas/FasL
The role of Fas and FasL can be understood by two mouse strains.
One is called MRL/lpr/lpr(Lpr has been identified as a defective Fas gene),
Another is called MRL/gld (mutation of FasL)
Most autoimmune diseases are polygenic, and affected individuals inherit genetic polymorphisms that contribute to disease susceptibility.
Susceptibility loci for autoimmune diseases
Among the genes that are associated with autoimmunity, the strongest associations are with MHC genes, especially class II MHC genes.
Examples of HLA-linked immunologic Diseases
Studies with knockout mice and patients have identified several genes that influence the maintenance of tolerance to self antigens.
Examples of Gene mutations that results in autoimmunity
Treatment of autoimmune diseases
When irradiated self-reactive T cells are infused to the blood, these T cells apparently elicit regulatory T cells specific for TCR variable-region determinants.
altered antigen peptide
Mice fed MBP do not develop EAE after subsequent injection of MBP,
However, the human clinical trials are in the early stages.
Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.
a. Th1 cells have been associated with development of autoimmunity.
b. Immunization of mice with IL-12 prevents induction of EAE by injection of myelin basic protein plus adjuvant.
c. The presence of the HLA-B27 allele is diagnostic for ankylosing spondylitis, an autoimmune disease affecting the vertebrae.
d. Individuals with pernicious anemia produce antibodies to intrinsic factor.
e. A defect in the gene encoding Fas can reduce programmed cell death by apoptosis