Robbin's: Transplant Rejection

Question 1

Rejection of allografts is largely due to

Answer 1

MHC molecules–> very polymorphic

Question 2

define allograft

Answer 2

same species–> not genetically identical

Question 3

define xenograft

Answer 3

diff. secies–>not genetically identical

Question 4

define syngeneic

Answer 4

same species–> genetically identical

Question 5

define autograft (isograft)

Answer 5

your ass skin to your arm

Question 6

two main mechanisms for which the host immune system responds to MHC molecules on the graft

Answer 6

Direct recognition

indirect recognition

Question 7

Define direct recognition

Answer 7

Host T cells rectly recognize MHC molecules on Graft DC’s bound to any antigen (cross reaction)
>If it is HLA A or B–> CTL activation–>kill the graft
> If it is HLA DR–> Cd4–> cytokines (IFNgamma)–>damage and delayed type hypersensitivity

Question 8

HLA genes involved in direct recognition

Answer 8

HLA A, B, DR

Question 9

Graft DC’s with MHC molecules bound to any antigen is thought to mimic…

Answer 9

Self MHC molecules bound to foreign antigen

Question 10

Define indirect activation

Answer 10

host CD4Tcells recognize antigen on MHC molecules only AFTER it has been picked up by the hosts own APC’s
>t cells specific for donor antigens acitvate B cells and antibodies are formed against the donor tissue

Question 11

major differences in Direct Vs Indirect path

Answer 11

direct= No B cell involvement or production of anti-donor Ab’s

indirect–> sampling of alloantigen after the peptides have been taken up by cell’s own APC’s where in direct itsTcells interacting with donor APC’s (DC’S)

Question 12

T cell mediated rejection takes 3 forms..

Answer 12

1. CTL’s kill graft cells
2. CD4 t cells release inflammatory cytokines resulting in graft damage (similar to a DTH reaction)
3. Activated macrophages (via IFN gamma) can injure graft vasculature

*ischemia and graft rejection is the result

Question 13

Ab mediated rejection MOA

Answer 13

Allogenic antibodies bind to graft endothelium and cause vascular injury by activation of compliment and activation of leukocytes.

Question 14

Hyperacute rejection MOA

Answer 14

PREFORMED anti-donor anti-bodies against graft tissue

and also mis-matched blood type/tissue type for which there would already be pre-formed ab’s

Question 15

hyperacute time frame

Answer 15

minutes to hours

Question 16

How can Hyperacute rejection happen

Answer 16

> blood type mismatch
individual was exposed to forgein HLA from a prior blood transfusion
multiparous women who have anti-HLA ab’s against paternal HLA encountered during preganacy
previous transplant rejection

Question 17

Time frame of acute rejection

Answer 17

days or weeks in a non-immunosuppressed host

Question 18

histo findings of cellular acute rejection

*occurs within the first months and presents as renal failure

Answer 18

mononuclear infiltrate (CD4 and CD8) DESTROYS PARENCHYMA (AND VESSELS) BY CYTOTOXICITY AND INFLAMMATORY REACTIONS

Question 19

histo findings of humoral acute rejection

Answer 19

vasculitis

Question 20

CNI with renal toxicity

Answer 20

cyclosporin

Question 21

how to distinguish from renal failure and renal Cyclosprin toxicity

Answer 21

renal biopsy

Question 22

Acute humoral injection is also known as

Answer 22

rejection vasculitis

Question 23

Acute humoral rejection path findings

Answer 23

vsculitis with endothelial cell necrosis, neutrophillic infiltration, deposition of antbody, compliment and fibrin and thrombosis

*ISCHEMIC NECROSIS OF RENAL PARENCHYMA

Question 24

know what happens in chronic rejection

Answer 24

IDGAF

Question 25

HSC’s are infused where following chemo/readiation

Answer 25

Peripheral Blood–>they then hone to their blood cells nicihes

Question 26

rejection of HSC’s is carried out by which cell types

Answer 26

T cells and NK cells that are resistant to chemo/radiaton

Question 27

GVHD occurs when…

Answer 27

immunologically competent t cells are given to a pt. who is immunocompromised

Graft cells recognize host cells as foreign and attack host cells

Question 28

Mismathches associated with GVHD

Answer 28

MINOR histocompatability complexes
organs with lots of lymphoid cells (liver)
non-irradiated whole blood

Question 29

ACUTE GVHD (days/weeks) attacks epithelial cells in what three target organs

Answer 29

Skin–> macropapular skin rash
Gut–> diarrhea
Liver–> high serum biliirubin

Question 30

Chronic GVHD manifestation

Answer 30

skin lesions simila to SS with other findings of various autoimmune diseases