23. Transplant Immunology

Question 1

allorecognition definition?

Answer 1

immunity that develops against the antigens (proteins, carbs, lipids) of another indiv of the same species

Question 2

direct presentation?

Answer 2

direct presentaiton of allogenic MHC molecule by APC in graft (acute cell rejection)

Question 3

indirect presentation?

Answer 3

presentation of processed peptide of allogenic MHC molecule bound to self MHC molecule (self APC) (chronic/acute rejection)

Question 4

after brain death, what is upregulated and lead to early-phase inflammatory processes during organ retrieval?

Answer 4

E-selectin, Hsp70, MCP-1, interstitial leukocyte invasion

Question 5

cold ischemic time (CIT), ischemia reperfusion injury (IRI) and inflammatory response all lead to what?

Answer 5

increased chemokines and other inflammatory responses during reperfusion of allografts

Question 6

what is the big problem with completely blocking inflammatory responses that lead to graft rejection?

Answer 6

then you also block HEALING

Question 7

three types of allograft rejection?

Answer 7

hyperacute: avoidable, antibody & complement mediated (screen to make sure pt is NOT immunized to donor)
acute: treatable, T cell mediated (macrophages) & antibody mediated (humoral)
chronic: not fully understood, T cell-driven anti-donor antibody, late consequence of initial injury? (very low activaiton of immune system make Abs over time that attack allograft, cells convert to fibroblasts, function of organ lost over time)

Question 8

chronic allograft nephropathy includes what pathologies?

Answer 8

transplant arteriopathy: w/intimal prolif, subintimal/medial smooth muscle prolif & fibrosis, & progressive luminal narrowing

transplant glomerulopathy: w/reduplicaiton of the glomerular BM, lesion typical of chronic antibody-mediated rejection (AMR)

global glomerular sclerosis and interstitial fibrosis/tubular atrophy

Question 9

immunosuppression right after transplantation:

Answer 9

maintenance (steroids, tacrolimus, mycophenolate mofetil, rapamycin, azathioprine, cyclosporine, belatacpet)

induction: basiliximab, daclizumab, thymoglobulin, campath, atgam, OKT3, belatacept

Question 10

categories of immunosuppressive agents?

Answer 10

induction agents: monoclonal or polyclonal Abs, admin IV immediately post surgery

primary immunosuppressants: CNIs from the cornerstone of immunosuppressive therapy

Adjuvant agents: one ore more meds RX in combo w/the CNI

Question 11

high risk for rejection (and thus needs more strong immunosupp therapies)?

Answer 11

highly sensitized
non-primary transplant
African american/hispanic ethnicity
cadaveric donor source
poor HLA match

Question 12

low risk for rejection (and thus needs less strong immunsupp therapies)?

Answer 12

nonsensitized
asian/caucasian
elderly
living donor source
good HLA match

Question 13

histocompatibility involves what?

Answer 13

antigens: ABO, HLA, other

measuring antigenic differences

risk assessment

Question 14

4 functions of HLA gene products?

Answer 14

1. determination of the repertoire of T cell antigen receptors (TCR) molecule
2. presentaiton of peptides to T cells
3. regulation of NK cell cytotoxic activity
4. fetal allograft protection

Question 15

ab detection methods for membrane based, peripheral leuks, or cell lines?

Answer 15

complement dependent cytotoxicity (CDC)
- negative is good, positive is very bad

flow cytometry

Question 16

ab detection methods for solid phase?

Answer 16

ELISA

flow cytometry (multiplex)

Question 17

causes of allosensitization?

Answer 17

• transfusion of blood products
• pregnancy
• prior transplantation
• severe infection
• autoimmunity