Sunday, June 29, 2014

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Summer Immunology- Block 3
Autoimmunity: Clinical Consequences
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KNOW type and Ag trigger of all autoimmune diseases!!

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autoantibodies don't necessarily lead to autoimmune disease

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Factors that result in an autoimmune response:

genetics
infections
environmental influences
hormones (especially estrogen)
age
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Autoimmune diseases classically considered to be Type II (or IV)- organ
specific, or Type III- systemic

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Type II autoimmune diseases:

organ specific
IgG and IgM
complement activation
Cytotoxic Type II diseases (others covered in previous lectures):
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hemolytic disease of the newborn, aka, erythrobastosis fetalis:

immune disease treated with an immunotherapy
Rh- mother and Rh+ infant Rh mismatch
Sunday, June 29, 2014
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No problems in the first pregnancy, just stimulates a T dependent generation of
memory B cells producing IgG antibody against RhD
Subsequent pregnancy with Rh+ fetus, maternal IgG can be transported
across the placenta, react with fetal Rh+ RBCs, and produce hemolytic
disease.
Treat with RhoGAM (human anti-RhD IgG Ab) at 28 weeks of gestation and
again within 24 hours after birth
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eliminates fetal Rh+ RBCs before they can generate RhD specific memory B
cells in the mother

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Agglutination (Coomb's) Tests:

Direct Coomb's test tests for autoimmune hemolytic anemia
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Patient RBCs + anti-immunoglobulin --> agglutination = Positive DIRECT
Coomb's Test

Indirect Coomb's test tests for whether a Rh- mother has been exposed to Rh+
RBCs and developed anti-RhD autobodies
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Patient Serum + test RBCs --> (incubate and wash) + anti-immunoglobulin --
> agglutination = Positive INDIRECT Coomb's Test

NONcytotoxic Type II diseases (see lecture slide):
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not every Type II autoimmune process results in decreased function or cell
death, can stimulate organ (ie, Grave's Disease)

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Autoantibodies may be found in some degree but play no apparent role in the
pathogenisis of disease (ie, Hashimoto's thyroiditis- Type IV)

presence of autoantibodies useful for diagnosis of Hashimoto's
immunofluoresence pattern for thyroglobulin:
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Hashimoto's = cytoplasm

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SLE = nuclei

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Type III autoimmune diseases:

systemic
IgG and IgM
complement activation
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Low serum C3 and C4 levels present in Type III diseases (and not in Type II)

Systemic lupus erythematosus (SLE):
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prototypical Type III disease

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common in women, indicate that estrogen influences human SLE

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Patient must have 4 of 11 systems to suspect lupus (see table on pg 279 of
manual)

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antinuclear antibodies (ANA) are present in most SLE patients and can be
detected with fluorescent microscopy

5 clinically pertinent ANA patterns (see lecture slide on ANAs)
peripheral/rim (anti-dsDNA) and speckled (anti-Sm) patterns are diagnostic for
SLE
severity of renal disease predicts most closely the outcome of SLE patients
detection of circulating immune complexes in serum also correlate with
increasing disease activity
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Type IV autoimmune diseases:

organ specific and systemic (?)
Type I Insulin Dependent Diabetes Mellitus (IDDM):
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Ag-specific T cell activation leads to pancreatic infiltration by lymphocytes

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Eventual destruction of islet beta cells results in progressive decline of insulin
levels

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Rheumatoid arthritis:
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nodules in joints

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bony erosions leads to malformation of hands, etc (not seen in osteoarthritis)