Type II Immunopathology (Ab mediated)

Question 1

Describe the molecular and cellular details of the immunologic mechanisms by which tissue damage occurs in a Type II (“cytotoxic antibody”) reaction.

Answer 1

Autoantibody

• activates complement to phagocytose (platelets) or release of the phagocytes’ lysosomal enzymes (myasthenia gravis)
• behaves as an agonist for a cell-surface receptor, e.g. Graves

Question 2

2. Give an example of a Type II mechanism disease of muscle, kidney, heart, red cells, platelets, lung, thyroid, pancreatic islets.

Answer 2

muscle - Attach ACh-receptor on muscle
kidney / lungs - Goodpasture (Ab to BM)
heart - Dressler, Ab to pericardial or myocardial antigens
Red cells - AIHA
platelets - ATP (Ab to platelet)
thyroid - Hashimoto's

Question 3

3. Describe the fluorescent antibody tests which would allow you to make the diagnosis of Goodpasture Syndrome, given: patient’s kidney biopsy, normal kidney biopsy, patient’s serum, and fluoresceinated goat antisera to human IgG and complement.

Answer 3

Incubate biopsies with patients serum, then add fluor-Ab. Look for LINEAR staining, not lumpy bumpy

Question 4

4. Distinguish between the “lumpy-bumpy” and “linear” immunofluorescent patterns in terms of the most probable immunopathologies they represent.

Answer 4

Linear = #2, it binds the BM
Lumpy = #3, it's forming an immune complex and simply getting stuck

Question 5

6. Given patient’s serum, fluorescent antibody to human immunoglobulins, and slices of normal kidney, describe how you could tell if the patient’s glomerulonephritis was due to Goodpasture Syndrome or SLE.

Answer 5

If good pasture, should get linear staining since the Ab will bind directly.
If SLE, Ab is to dsDNA. No apoptotic cells, no stain.

Question 6

7. Describe how antibody-mediated tissue damage could result from: The innocent bystander phenomenon.
   Coupling self antigen with a foreign antigenic “carrier”. Exposure of a sequestered antigen.
   Inadequacy of regulatory T cells.

Answer 6

Innocent bystander example: Ab to drug, drug binds RBC, RBC gets lysed by complement

Illicit help: B cell binds self + foreign epitope
It then ingests the fusion protein
Foreign epitope is presented to Th2 MHCII
Th2 secretes IL-4, etc.
B cell is activated, secretes antibody to self

Sequestered: Ag cannot get out into the general system, so not normally immunogenic
If an immune response does get initiated, then the response can usually get into the place where the antigen was sequestered.

Question 7

8. Identify “Rheumatoid Factor” and describe its molecular nature.

Answer 7

IgM anti-IgG!

Question 8

9. Name a condition in which antibody stimulates rather than inhibits or harms its target cell.

Answer 8

Graves/LATS: Ab to TSH –> release of thyroid hormones

Inappropriate tachycardia: autoantibodies to the β-adrenergic receptor, which are stimulatory, like epinephrine. Reversible w/ beta blocker propranolol)

Question 9

10. Discuss how the Aire gene is involved in preventing autoimmune disease.

Answer 9

Aire = TF that up regulates random proteins to be expressed in thymus so T cells are negatively selected against self