Type III Immunopathology (Immune Complexes)

Question 1

1. Arthus reaction and serum sickness are local and general manifestations of immune complex disease; describe the mechanism of tissue damage. Discuss why this could reasonably be called ‘innocent bystander injury.’

Answer 1

On booster administration, complexes immediately begin to form locally.
They activate complement and neutrophils are attracted;
Causes local inflammation

Question 2

2. Indicate the critical size at which immune complexes get stuck in basement membranes.

Answer 2

Large: cleared by RES
Small: can’t activate comp
Medium: about a million daltons can activate complement but are below the size that is rapidly removed by the RES. Medium also can’t pass readily through the BM of small blood vessels.

Question 3

3. Describe ‘one-shot’ serum sickness. Make a chart showing antigen, antibody and immune
   complex levels in relation to relative time and to symptoms.

Answer 3

Shortly after injection of the animal serum, there’s excess Ag w/ no complexes
As antibody production inc, equivalence between the antibody in circulation and the remaining antigen is achieved, and large complexes form.
Just before that, though, there will be complex formation in relative antigen excess, so they are smaller than optimal-proportions complexes; in fact, they may be just the size to get lodged in basement membranes.

That is the time that symptoms begin. They persist a week or more, until enough antibody has been made to form the large complexes that are readily cleared by the RES.

Graph: picture 3 large humps (Ag, IC, Ab)

Question 4

4. Discuss the types of tissues in which damage is most likely to occur from deposition of immune complexes.

Answer 4

complexes will be trapped most in capillary beds where there is most filtration of blood; that is, where there is net outflow of fluid. For example, any location that must be kept wet qualifies:
Joints
Pleura
Peritoneum
Skin
Choroid plexus
Kidney

Question 5

5. Discuss the immunological mechanism of a typical Type III disease involving exogenous antigen.

Answer 5

IC get stuck in the basement membrane.
Complement is activated 
Classical cascade ensues
C3a and C5a attract neutrophils
Neuts release a variety of inflammatory factors, including the proteases cathepsin G and elastase; and hydrogen peroxide, which by activating metalloproteinases also contributes to the proteolytic degradation of the basement membrane.

Question 6

6. Discuss how urticaria (hives) could result from interaction of antigen with either IgE or IgG antibody.

Answer 6

C3a and C5a will, as anaphylatoxins, release histamine and other mediators from mast cells, increasing the inflammatory reaction (►and they may cause hives).

Question 7

7. Name 3 different kinds of human immune complex disease or problem and indicate a type of antigen involved in each condition.

Answer 7

Exogenous

Endogenous

Question 8

8. 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.

Answer 8

cryoglobulins appear when serum is kept 24 hours in the refrigerator (immune complexes are less soluble in the cold.) These are ‘mixed’ cryoglobulins, being antigen + antibody; single- component cryoglobulins are the monoclonal product of a clone of malignant B cells.
They indicate immune complexes in the blood

Question 9

9. Define rheumatoid factor and discuss its components.

Answer 9

IgM anti-IgG

Question 10

10. Discuss the pathogenesis of post-streptococcal glomerulonephritis. Describe the diagnosis of this condition by fluorescent antibody technique, and name the pattern of resulting fluorescence.

Answer 10

ICs get caught up in the kidney, “the great filter,” esp. when ABX were not used. Sx begin 10-14 days after infection (nausea and vomiting, fever, malaise, hypertension, reduced urine output, hematuria, joint pain and rash). Serum complement levels are decreased. Diagnosis is by history and renal biopsy. Treatment is symptomatic and supportive, and includes antibiotics.

Sections of the kidney are stained with fluorescein-labeled goat antibodies to human immunoglobulin classes or subclasses.
The basement membrane is visualized as the site of tiny clumps of antigen-antibody complex, in a pattern that is called ‘lumpy-bumpy.’
A fluorescent antibody to complement (and probably Ag) will usually reveal the same pattern.

Question 11

11. Discuss the pathogenesis of hypersensitivity pneumonitis, for example Farmer’s Lung.

Answer 11

After chronic inhalation exposure to a bug in hay, the farmer develops serum IgG antibodies.
One day, he inhales enough antigen that antigen-antibody complexes form in the lungs as the mold proteins diffuse through the alveoli into the capillaries.
Complement and neutrophils cause the symptoms
An acute attack will start 4 to 8 hours after the exposure, with shortness of breath, a dry cough, malaise, fever, and tachycardia.
Most episodes are rather more chronic, with similar but milder symptoms, to which arthritis is sometimes added.
With time, T cell-mediated inflammation begins and eventually predominates in more serious cases. There are Th1 cells present, and granulomas also become apparent, suggesting Th2 cell involvement as well. So Type III evolves into Type IV, and gets more destructive and harder to treat.