Immunopathology Type 2, Autoimmunity

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

When you activate the immune system, you activate complement and that lyses cells. So it’s complement mediated damage to tissues. Also neutrophil mediated tissue destruction

Question 2

Give an example of a Type II mechanism disease of muscle

Answer 2

Myasthenia Gravis- autoimmune response against the acetylcholine receptors

Treatment: immunosuppression, neostigmine-
related drugs to increase the effectiveness of residual Ach, and IVIG

Question 3

Describe the tests which would allow you to make the diagnosis of Goodpasture’s Syndrome

Answer 3

Linear kidney immunofluorescence, glomerulonephritis,

Kidney biopsy, if there is IgG in the biopsy, the anti IgG will stain the kidney red where teh human antibody is (direct test)

Using a normal kidney, you can wash the normal kidney with the patient’s blood and observe the following immunofluoresences

Question 4

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

Answer 4

Linear- Antibodies specifically against kidney BM (goodpastures) (Type II)

Lumpy-Bumpy- Antibodies trapped in the glomerulus that is a result of them being unable to be filtered by the kidney. Immune complex deposition pattern (Type III)

Question 5

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’s Disease or SLE.

Answer 5

For SLE, the glomerulonephritis is actually type III, so it’s lumpy bumpy, because it’s just deposition of antibodies in the kidney chronically.

Question 6

Describe how antibody-mediated tissue damage could result from the innocent bystander phenomenon

Answer 6

If there is an antibody response against a foreign antigen that is attached to self tissue.

Question 7

Identify “Rheumatoid Factor” and describe its molecular nature.

Answer 7

Marker of Rheumatoid arthritis. (T cell mediated attacking of the lining of joints)

can be detected by adding the patient’s serum to microscopic beads that are coated with normal human IgG. RF makes the beads agglutinate; ►it is IgM anti-IgG!

Question 8

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

Answer 8

In Grave’s disease, antibody stimulates thyroid receptors, acting as ligand (TSH). However, the normal physiological controls to reduce thyroid signalling is not applicable, so you have hyperthyroidism

Question 9

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

Answer 9

AIRE genes express various molecular patterns resemble self antigen, so that in t cell maturation and selection, we can avoid self reaction.

Question 10

Give an example of a Type II mechanism disease of Kidneys

Answer 10

Goodpasture- Type IV Collagen in Basement membrane in the glomerulus, leading to destruction of

Question 11

Give an example of a Type II mechanism disease of the heart

Answer 11

Agonist to Beta adenergic receptors on the heart (Innapropriate tachycardia)

Rheumatic Heart Disease (Strep infection leads to cross reactivity to heart tissue endothelial lining/laminin)

Dressler Syndrome- Post heart attack antibodies to pericardial or myocardial antigens

Question 12

Give an example of a Type II mechanism disease of Red Cells

Answer 12

Autoimmune Hemolytic Anemia

Question 13

Give an example of a Type II mechanism disease of Platelets

Answer 13

.

Question 14

Give an example of a Type II mechanism disease of the lung

Answer 14

Goodpasture- Type IV Collagen in Basement membrane, leading to pulmonary hemorrhage

Question 15

Give an example of a Type II mechanism disease of the Thyroid

Answer 15

Graves (hyperthyroidism) and Hashimotos (Hypothyroidism)

Question 16

Give an example of a Type II mechanism disease of Pancreatic islets

Answer 16

Type I Diabetes

Question 17

Describe how antibody-mediated tissue damage could result from cross reaction of a foreign antigen to self

Answer 17

THink rheumatic fever, where following a strep infection (or other infections), it cross reacts with heart tissue causing Type IV

Question 18

Describe how antibody-mediated tissue damage could result from coupling self antigen with a foreign antigenic “carrier,”

Answer 18

If a self b lymphocyte isn’t killed, it normally won’t be an issue because you won’t get the t response necessary to mount an immune response. However, if somehow a foreign antigen is coupled with that same self antigen, THAT can mount a response after presentation of the coupled epitope, because the foreign epitope is presented but the self Ig is produced.

Question 19

Describe how antibody-mediated tissue damage could result from exposure of a sequestered antigen

Answer 19

So there are some tissue in our body that isn’t normally seen by developing t cells (think Dresslers), so following tissue injury, the body is suddenly exposed to this “foreign” antigen and we get a type II response

Question 20

Describe how antibody-mediated tissue damage could result from inadequacy of regulatory T cells

Answer 20

Well, I understand that Treg downregulates the activity of T1 and T2, which are the pro inflammatory t lympocyptes, so their inability to downregulate them could be damaging. I think I’m missing something but I don’t see how this is related to autoimmunity.