Type 3 Immune Complex Disease

Question 1

What is an Arthus reaction? Recall a classic example of it

Answer 1

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
  • Resolves in 24ish hrs
• Remember that sore arm after your last flu shot?, yeah that’s the symptom)

Question 2

How does tissue damage occur in Type III immunopathology (generally)?

This is an important concept, without it, you wont have a foundation for just about every other card.

Answer 2

Type III Tissue Damage

• Immune complexes form that are large enough to activate complement, but small enough to where they are not readily removed by RES (reticuloendothelial system)
• End up getting trapped in the BM (basement membrane) where they continue to activate complement
  
  • Attracts PMN’s and they release inflammatory factors that activate MMPs
  • MMP contributes to proteolytic degradation of the BM
• Nearby cells/tissue are often inocent bystander victims

Question 3

What is Serum Sickness?

Answer 3

Serum Sickness: When animal serum is used to treat disease

1. Injection has initial antigen excess, No Ab response yet
2. Ab production begins to increase, exponentially
   
   • Complexes form that are large enough to induce complement but not large enough (yet) to be cleared by RES (reticuloendothelial system)
     
     • leads to fever, malasise, rash, arthralgia 10-14 days after injection
3. Eventually Ab saturate the blood and complexes are large enough to be excreted efficiently by RES

Question 4

What is the critical size at which immune complexes get stuck in basement membranes?

Answer 4

A complex that is around 1,000,000 daltons

Review:

• Small immune complex: 1 antigen with 1-2 Abs cannot activate complement -> harmless
• Intermediate: 1,000,000 daltons - activates complement, but not efficiently cleared by RES, and cannot pass through BM
  
  • continuous activation of complement (tissue damage)
• Large complexes activate complement but are efficiently removed by the RES so this is normal immune response

Question 5

What types of tissues are the most likely to be damaged by Type III immunopathology and why?

Answer 5

Complexes more likely to be trapped in capillary beds where there is most filtration of blood (net outflow of fluid), any place you have to keep wet.

• 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

Question 6

Name 3 different kinds of human complex disease and indicate the type of antigen involved in each condition.

Answer 6

• 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.
• Rheumatoid Arthritis
  
  • Antigen involved: patient’s own IgG, and they make anti-IgG IgM against it –> again, found in joints.

Question 7

1. What would you call “fluffy precipitate”?
2. What is the most likely composition of it?
3. What does it indicate (broadly)?

Answer 7

1. Fluffy precipitate = Cryoglobulins
   
   • Immune complexes seen in serum 24 hours in fridge b/c less soluble cold
2. Single component cryoglobulin is the monoclonal product of a clone of malignant B cells.
3. Old way to detect immune complexes in blood.

Question 8

What is Rheumatoid Factor (RF)

Answer 8

RF: 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

Question 9

Post-Streptococcal Glomerulonephritis

1. Briefly describe the pathophysiology
2. Outline procedure to diagnose it, and what pattern you would see on an immunoflorescence slide

Answer 9

1. Antigen involved: Antibodies are complexed with Streptococcus pyogenes (follows after GAS infection), and is stuck in membrane of kidney, the great filter
2. Kidney biopsy
   
   • Atleast one glomerulus placed on slide and overlaid with fluorescent Ab to human Ig.
   • Under UV microscope, BM is seen as site of tiny clumps of antigen-antibody complex, in a pattern called “lumpy-bumpy”

Question 10

What is the pathogensis of Hypersensitivity Pneumonitis, for example in Farmer’s Lung

Answer 10

• Farmer’s chronic exposure to Actinomycetes found in moldy things, like hay
• Extra damp day causes drying via evaporation and spore release
• Inhaled spores complex w/ serum IgG activate complement
• PMN’s recruited -> inflammation of lung