9 BL Immunopathology type III Flashcards
Arthus reaction
when pre-existing Ab are present and pt is given a booster immunization –> complexes form, activate complexes and attract neutrophils w/ symptoms noticeable 4-6 hours later (remember that sore arm after your flu shot?, yeah that’s the symptom)
Arthus reaction and serum sickness are local and general manifestations of immune complex disease; describe the mechanism of tissue damage
“innocent bystander injury”
• Tissue damage from Type III Immunopathology because:
when immune complexes are formed, but stuck in BM of tissues, they still continue to activate complement→
which initiates the cascade (remember C3b and C5a for opsonization and attraction of PMNs, respectively?) →
These PMNs arrive and also release inflammatory factors, including proteases, capthepsin G, and elastase, as well as hydrogen peroxide.→
This activates MMPs which contributes to proteolytic degradation of BM. →
So if you happen to be a cell near the area of this inflammation attack, sorry, you’re gone, too (Innocent bystander injury).
Indicate the critical size at which immune complexes get stuck in basement membranes.
- If IgG or IgM Ab-Ag complex is formed, they tend to be polyclonal so they complexes are LARGE, thereby easily cleared by RE system.
- SMALL complexes (i.e. 1 antigen to 1-2 Abs) are too small to activate complement → harmless.
- If complexes are “right size” → can activate complement but can’t be removed by RE system and they are too large to pass through basement membranes of small b.v.→ They get stuck! and activate complement by binding C1q and initiates cascade → Inflammation!
Describe ‘one-shot’ serum sickness.
• One-shot serum sickness is the side effects (fever, malaise, rash, itch, and arthralgia) that occurs 10-14 days after administration of one dose of animal antisera to treat an infectious disease.
Discuss the types of tissues in which damage is most likely to occur from deposition of immune complexes
• Complexes more likely to be trapped in capillary beds where there is most filtration of blood (net outflow of fluid)
○ Joints; b/c lubricating synovial fluid
○ Pleura; b/c pleural fluid to keep lungs inflated
○ Peritoneum; b/c peritoneal fluid keeps guts from squeaking
○ Skin; b/c evaporation (mostly in legs where BP is higher)
○ Choroid plexus; b/c CSF
○ Kidney, b/c filters plasma volume
Discuss how urticaria (hives) could result from interaction of antigen with either IgE or IgG antibody.
- If the antigen is interacting with IgG, then complement will be activated and as a result C3a and C5a will form. These complements are also anaphylatoxins, so they will cause a release of histamine and other mediators to increase inflammation, inc. producing urticaria (HIVES!).
- If luck is not with the patient and IgE is also produced in response to the antigen, mast cells will respond too by releasing histamine and causing even more goshdarn hives.
indicate a type of antigen involved in each condition:
• Post-Streptococcal Glomerulonephritis
○ Antigen involved: Antibodies are complexed with Streptococcus pyogenes (follows after GAS infection), and is stuck in membrane of kidney, the great filter.
indicate a type of antigen involved in each condition:
• Hypersensitivity Pneumonitis
Antigen involved: Actinomycetes, filamentous bacteria which are found in moldy hay and silage.
indicate a type of antigen involved in each condition:
Rheumatoid Arthritis
Antigen involved: patient’s own IgG, and they make anti-IgG IgM against it –> again, found in joints.
indicate a type of antigen involved in each condition:
Systemic Lupus Erythmatosus, SLE
○ Antigen involved: dsDNA and histones, patients make IgG against this.
indicate a type of antigen involved in each condition:
Primary Glomerulonephritis
aka IgA Nephropathy
○ Antigen involved: unglycosylated IgA1 (from IgA, but has unusually long hinge regions but no terminal sugars of carbohydrate chain, which creates new epitope that ends in N-acetyl-galactosamine). Abs are IgA and IgG.
Discuss the meaning of finding a fluffy white precipitate in a patient’s serum after a day in the refrigerator. Include the name used for such precipitates, the most likely composition, and the interpretation of the phenomenon.
Fluffy precipitate = cryoglobulins,
which are immune complexes seen in serum 24 hours in fridge b/c less soluble cold (if measuring for Type III immunopathology).
This is an old way to detect immune complexes in blood. Typically they are mixed cryoglobulins (antibody and antigen), but a single compenent cryoglobulin is the monoclonal product of a clone of malignant B cells.
Define rheumatoid factor and discuss its components.
The RF is anti-IgG IgM, and it is found in patients with rheumatoid arthritis. It is tested for by adding the patient’s serum to IgG coated microbeads, where IgM anti-IgG will agglutinate the beads.
post-streptococcal glomerulonephritis:
Describe the diagnosis of this condition by fluorescent antibody technique, and name the pattern of resulting fluorescence.
Diagnosis: Kidney biopsies containing at least one glomerulus are placed on slide and overlaid with fluorescent Ab to human Ig.
When viewed under UV microscope, BM is seen as site of tiny clumps of antigen-antibody complex, in a pattern called “lumpy-bumpy”
Lumpy bumpy vs Linear
Lumpy bumpy: type III - stuck in bm
Linear: type II - directly attack bm (Goodpasteur!)
