Hypersensitivity Type III
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Type III Hypersensitivity
Pathogenesis of immune complex-mediated hypersensitivity:
Type III Hypersensitivity Examples:
Vasculitis
Inflammation of the vessel walls.
Is a common manifestation of type III hypersensitivity.
Review:
Small vessel, medium vessel, large vessel vasculitis
Arthritis
Occurs when immune complexes deposit in the synovial joints.
Post-infectious glomerulonephritis
Inflammation of the renal glomeruli, is associated with Staphylococcus bacterial infection (and, increasingly, Streptococcus infections).
Review: Post-infection glomerulonephritis
Review:
nephritis.
Local Arthus Reaction
Produces localized vasculitis and tissue necrosis; rarely, it is associated with tetanus or diphtheria-containing vaccines.
It can be produced by re-injecting antigens too soon after initial exposure:
The antigens form immune complexes with circulating IgG antibodies.
Then, the immune complexes activate complement and recruit inflammatory cells, including neutrophils and mast cells.
Inflammatory cell degranulation releases cytokines, enzymes, and other molecules that produce local inflammation at the injection site, which is marked by pain, swelling, and redness that typically subsides after a few days.
Hypersensitivity pneumonitis, aka, allergic alveolitis, is a type III hypersensitivity reaction that takes place in the lungs.
Systemic Serum Sickness
Manifests throughout the body.
Serum sickness can be induced by older vaccines that used antibodies from other species, such as horses and rabbits; though rare, it can also occur after transfusions. Anti-venom reactions can occur when, for example, anti-snake venom treatment is administered to a previously sensitized individual. Newer anti-venom treatments avoid this reaction.
Graphically:
X-axis = "Time in Days"; Y-axis = "Plasma levels"
At time 0, show that plasma levels of foreign proteins spike immediately after administration, then slowly decline for a period; Initially, plasma antibody concentration is low.
Then, show that as production of plasma antibodies increases, immune complexes are formed; thus, the concentration of foreign protein is rapidly reduced.
Furthermore, show that the appearance of serum sickness symptoms coincides with immune complex formation, and typically resolve on their own.
Common manifestations of serum sickness include: blotchy skin rashes, joint pain, peripheral edema, and fever.
Systemic Lupus Erythematosus (SLE)
Genetically-influenced disorder caused by autoantibodies that target self-antigens.
SLE is associated with a wide variety of autoantibodies, some of which are specific to the disorder; furthermore, some of the autoantibodies are correlated with specific outcomes.
Some key autoantibodies include:
Antinuclear antibodies, which target components of host nuclei; these are non-specific to SLE.
Anti-double stranded DNA antibodies, which are specific for SLE and may be associated increased renal damage;
Anti-sm antibodies, also specific to SLE, may be associated with increased pulmonary arterial hypertension;
Antiphospholipid antibodies, which are non-specific and are associated with thrombosis, hemolytic anemia, and, possibly, problematic pregnancies.
Anti-Ro and anti-La antibodies are commonly found in SLE patients, but are not-specific; importantly, anti-La antibodies may cross the placenta and interfere with fetal heart development.
Clinical manifestations of autoantibody actions include:
Lupus nephritis, of which there are 6 patterns of glomerular damage;
Here, we indicate that the most common includes widespread destruction characterized by thickened "wire loops" and necrosis; often, crescent-shaped damage in Bowman's capsule is also visible.
SLE produces specific rash patterns; the malar rash pattern, also known as the "butterfly rash," and, "discoid rash," which is disc-shaped and tends to be scalier.
The cardiovascular system may also be affected. Here, show Libman-Sacks endocarditis, in which sterile vegetations form along the margins of the valve leaflets; recall that sterile vegetations are especially prone to breaking free and embolizing.
Pericarditis and/or peritonitis are also common, though not shown here.
Common environmental triggers for SLE flares include: ultraviolet light, some medications, cigarette smoking, and certain viral infections.
Some of the immune-complex mediated symptoms of systemic lupus erythematosus can be treated with hydroxychloroquine (originally used to treat malaria) and corticosteroids, such as Prednisone, which dampen the immune response.
Review: SLE