Immunology - Type IV Hypersensitivity (Graft Versus Host Disease, GvHD))

Question 1

cause

Answer 1

type of transplant rejection caused by immunocompetent donor T cells reacting against recipient MHC I “foreign” antigens, variable time course of symptoms, common targets skin + liver + intestine + epithelial tissue

Question 2

pathology - CD4+

Answer 2

donor CD4+ T cell recognizes recipient MHC II as foreign and is activated -> cytokine release -> recipient macrophage and CD4+ recruitment -> cytokine response (tumor necrosis factor (TNF) alpha possible cause of “metabolic wasting”)

Question 3

pathology - CD8+

Answer 3

donor CD8+ T cell recognizes recipient MHC I as foreign and is activated -> Fas + perforin mediated cytotoxicity (majority of tissue destruction via CD8+ T cells)

Question 4

graft versus leukemia (GvL)

Answer 4

beneficial due to ability to help eliminate recipient’s hematopoietic cancer cell line

Question 5

risk factors

Answer 5

liver and bone marrow transplants (rich in lymphocytes), T cell immunodeficient individuals and newborns

Question 6

signs and symptoms

Answer 6

metabolic wasting/failure to thrive, maculopapular rash, jaundice, bloody diarrhea, hepatosplenomegaly

Question 7

diagnosis

Answer 7

histological analysis of easily biopsied tissue in individual with history of transplantation, liver + skin + GI tract (becomes edematous seen in coronal plane CT scan, florid cryptitis (neutrophils infiltrating the crypt wall)+apoptotic debris at crypt bases seen in colonic biopsy) most helpful in chronic and indolent disease, constellation of clinical symptoms

Question 8

treatment

Answer 8

medications (prophylaxis (ie cyclosporine, methotrexate), site directed corticosteroids (topical for primary skin manifestation, non-absorbable (ie budesonide, beclomethasone) for GI involvement), prevention (proper donor, recipient human leukocyte antigen (HLA), MHC/MiHA (minor histocompatibility antigen) matching, irradiation of transfused blood products)