BL - Immunopathology Type III Immune Complexes Flashcards
Critical size at which immune complexes get stuck in basement membranes
About a million daltons (5 or 6 antibody/antigen interactions)
One-shot serum sickness
Occurs 10-14 days after administration of large dose of antisera. Patient develops fever, malaise, rash, itch, arthralgia, hives.
Mechanism of tissue damage in Arthus reaction and serum sickness
Complexes made following administration or exposure to exogenous antigen, complexes get stuck in basement membrane, complexes activate complement locally which attracts neutrophils and causes an inflammatory reaction.
Exam: tender lymphadenopathy, urinalysis with increased RBC casts and protein. CRP and ESR increased. Total hemolytic complement decreased.
Types of tissues most likely to be damaged from deposition of immune complexes
Tissues where there is net outflow of blood - because there is most filtration of blood: joints, pleura, peritoneum, skin, choroid plexus (makes CSF), and kidney
Immunological mechanism of type III disease involving exogenous antigen
Large complexes of Ag/Ab formed in a situation of relative antigen excess after exposure to large dose of exogenous antigen. Complexes of a particular size (about a million daltons) are large enough to activate complement but too small to be removed by RES so they get stuck in basement membrane and cause inflammatory reaction.
Urticaria from IgE or IgG
IgE or IgG in immune complexes can activate complement, C3a and C5a as anaphylotoxins release histamine and can cause hives.
4 examples of diseases with exogenous antigen
Serum sickness
Post-streptococcal glomerulonephritis
Hypersensitivity pneumonitis (ex. Farmer’s lung)
Arthus reaction
3 examples of diseases with endogenous antigen
Rheumatoid arthritis
Systemic lupus erythematosus
IgA nephropathy
Cryoglobulins
Seen as “white fluffy precipitate” after patient’s serum is kept in refrigerator for 24 hours.
Mixed cryoglobulins: antigen + antibody
Single-component cryoglobulins: monoclonal product of clone of malignant B cells
Rheumatoid factor
IgM antibody to patient’s own IgG.
Present in rheumatoid arthritis (and some other conditions). Levels correlate only slightly with disease activity.
Tested for by adding patient’s serum to IgG-coated microbeads: RF will agglutinate beads.
Post-streptococcal glomerulonephritis
After infection with group A strep (ex. strep throat, scarlet fever, skin impetigo). Kidney most affected.
S/S: nausea, vomiting, fever, malaise, hypertension, reduced urine output, hematuria, joint pain, rash.
Serum complement levels decreased. Dx by renal biopsy and history.
Pathogenesis of hypersensitivity pneumonitis
Chronic exposure by inhalation causes farmer to develop serum IgG antibodies. Then when exposed to mold spores, enough antigen is inhaled that Ab/Ag complexes start to form in lung. Complement and neutrophils cause symptoms – acute attack starts within 4-8 hours after exposure, but most episodes are more chronic.
With time, T-cell mediated inflammation begins and predominates. Th1 cells, granulomas present (suggests Th2 involvement) – type III evolves into type IV.
Renal biopsy in glomerulonephritis
Section of kidney containing glomerulus stained with fluorescent-labeled goat antibodies to Ig classes.
After fixation, basement membrane can be visualized with UV microscopy as lumpy bumpy pattern.
Timing of symptoms of serum sickness (relative to antigen/antibody/immune complex levels)
Shortly after injection: antigen excess, no or only very small complexes
Right before the equivalence point – complex formation in relative antigen excess = smaller than optimal-proportioned complexes, so they get stuck in basement membranes. Symptoms begin.
As time passes, equivalence between Ab in circulation and Ag is achieved – this is when large complexes form that can be removed by RES
Symptoms of serum sickness persist a week or more until enough Ab has been made to form complexes large enough to be removed by RES
Systemic lupus erythematosus (SLE)
Severe dysregulation of immune system. Genetic as well as environmental.
IgG antibody to dsDNA and histones H2, H3, H4
dsDNA immune complexes deposit preferentially in kidney, causing glomerulonephritis
Exposure to UV radiation damages cells, causes them to release dsDNA and form immune complexes in bloodstream.
