Ch 6: Immunopathies (Part 4 - Transplant rejection and Amyloid)

Question 1

How can transplant rejection occur?

Answer 1

Allorecognition - where recipients immune system recognizes self vs. donor cells

Rejection:
Acute cellular
Antibody mediated

Organ specific:
Kidney
Bone marrow

Question 2

Describe the direct and indirect pathway of allorecognition.

Answer 2

Direct pathway:
Donor APC presents Ag to CD4 and CD8s activating them leading to endothelitis and damage

Indirect pathway:
Recipient’s APC presents Ag to CD4
CD4 helpers release IFN-y activating macrophages
CD4 helper activate B-cells which release Abs leading to endothelial injury

Question 3

What happens during a hyper acute rejection?

Answer 3

Occurs within minute to hours

Mediated by preformed antibodies

Marked inflammation followed by thrombotic microvasculopathy

Question 4

What happens during an acute and chronic Ab-mediated rejection?

Answer 4

Acute Ab-mediated rejection:
Inflammation with complement C4d breakdown product

Chronic:
fibrosis with primary effect on vessels

Question 5

What happens during an acute cellular rejection?

Answer 5

It is a T-cell mediated process
Acute cellular rejection within days, month, years of transplant
C4D stain will tell us the difference b/w acute cellular rejection and acute Ab-mediated rejection

Question 6

What drugs can we give a transplant patient? What are we treating with this drugs?

Answer 6

Corticosteroids = immunosuppressive

Tacrolimus = treats T cell mediated cellular rejection

Rituximab (anti CD20 recombinant ab) = treats Ab-mediated (humoral) rejection
Also immune globulin can be used

Question 7

What is the downside of using the transplant drugs?

Answer 7

Issues with immunosuppression

More prone to infections
Viral = polyomavirus, cytomegalovirus
fungal, and bacterial

More prone to tumors:
Viral induced = lymphomas, Kaposi sarcoma
Squamous carcinomas

Question 8

What is a hematopoietic stem cell transplant?

Answer 8

Therapy for hematologic malignancies and other conditions
Ablative chemotherapy and radiation destroys recipient bone marrow

Brand new immune system

Question 9

What is Graft-vs-host dz (GVHD)?

Answer 9

T-cell mediated
Receive transplant with other’s immune cells that are now attacking your own cell b/c they don’t recognize it

Skin = rash --> desquamation
Liver = jaundice (attacking RBC) --> cholestasis 
Intestines = Bloody diarrhea (attaching intestinal crypts) --> strictures