Immunology 10: Transplantation

Front 1

autograft

Back 1

graft from one location on an individual to another location

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syngeneic

Back 2

grafts between genetically identical indv

Front 3

allogeneic

Back 3

gratsb/t genetically non-idential individuals of the same species

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xenogeneic

Back 4

grafts b/t indv of diff species

Front 5

if T cells from a sensitized donor are injected into a naive recipient, what is the result? and what does tha tmean?

Back 5

accelerated rejection

means that second set rejection is cell mediated

Front 6

would graft from inbreb parental strain be rejected by F1 hybrid?

Back 6

no

Front 7

would graft from F1 hybrid be rejected by inbred parental strain?

Back 7

yes

Front 8

what is a rule for regrafting?

Back 8

new graft must not share foreign MHC with previously failed graft or will have acute rejection

Front 9

why will acute rejection occur in regrafting?

Back 9

preexisting antibodies
primed T cells

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3 types of graft rejection

Back 10

hyperacute
acute
chronic

Front 11

hyperacute rejection

Back 11

preformed antibodies bind vascular endothelium, activate complement

complement attracts neutrophils which attract lytic enzymes that destroy tissue

platelets adhere to injured tissue causing vascular blockage

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acute rejection

Back 12

CD8 T cells attach endothelial cells

CD4 T cells activate MAC which leads to tissue damage and inflammation

Front 13

chronic rejection

Back 13

2 types
1. T cell mediated: smooth muscle cell proliferation and luminal occlusion

2. antibody mediated: slow tissue damage

Front 14

does rejection require MHC disparity?

Back 14

no

Front 15

origin of minor histocompatinility antigens

Back 15

polymorphic self proteins that differe in aa sequence

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are mismatches in MHC Class 1 or 2 more imp?

Back 16

MHC Class II has more of a bad effect

Front 17

2 types of alloantigen recognition

Back 17

direct
indirect

Front 18

direct alloantigen recognition

Back 18

T cell recognizes unprocessed MHC moluecule on donor allograft

Front 19

indirect alloantigen recogntion

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T cell binds to MHC derived peptide presented by host MHC following processing of donor MHC by host APC

Front 20

production of anti-alloantigenic Ig

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from stimulation by the indirect pathway of allorecogntiion

CD4 T cell directly interacts with MHC on normal recipient cell but also intreacts with a B cell that has bound and processed MHC antigens

Front 21

how --activation of CD4 T cells by endothelial cell damage

Back 21

injury of EC leads to release of IL-1alpha and IL-1beta

these 2 cytokines activate T cells to make IFNhamma and IL-17

Theses t cell cytokines increase T cell activation and recurit new T cells

Front 22

what are immunosuppressive therapies targeted towards?

Back 22

immune cell fxn, migration, activation

devlopment of antigen specific T suppressor cells

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corticosteroids:

Back 23

anti inflammatory and mimic glucocorticosteroids made in adrenal cortex

Front 24

cytotoxic drugs

Back 24

interfere with DNA replicaton so kill proliferating cells

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microbial products

Back 25

inhibit signaling pathways of T cell activation

Front 26

how do steroids work?

Back 26

receptors are found in the cytoplasm complexed with a protein Hsp90

steorids cross cell membrane and bind

steroid-receptor can cross into nuclear membrane

in the nucleus, steroid receptor binds to specific gene regulatory sequences and activates transcription

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effect of IL-2

Back 27

stimulate growth of T cells

Front 28

3 effects of corticosteroid therapy

Back 28

1. reduce production of IL-2
2. inibit migration of inflammatory cell to sites of inflammation by reduction adhesion moelc expression
3. promote apoptosis of leukocytes and lymphocytes

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how to reduce production of IL-2

Back 29

by reducing other cytokines necessary (ex. IL 1,3,4,5, TNF alpha)

Front 30

how cyclosporine A and FK506 work

Back 30

bind to calcineurin, which blocks its ability to be activated by calcium

this blocks ability to activate NFAT which is requried for activation of gene expression needed to fully activate T cells

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calcineurin

Back 31

a phosphatase that activtes NFAT which migrates to the nucleus and binds to AP-1 to form an active transcription factor which activates IL-2 gene--> clonal expansion

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sites of action for therapeutic drugs for transplantation

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TCR engagement and costim interactions

intracellular signaling molec

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example of drug that affects TCR engagement and costim interactions

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anti CD40L

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exmple of drug that affects intracellular signaling molec

Back 34

cyclosporin A

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ex of T regulatory cells

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CD4

CD25

Front 36

HOw do T regulatory cells recognize donor antigen when donor alloantigen enocuntered?

Back 36

through indirect pathway

Front 37

how do t regulatory cells recognize completely mismatched allografts?

Back 37

as an allopeptide bound to a recipiemt MHC Class II on recipient APCs

Front 38

functional activity of T reg cells depends on

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CTLA4

GITR

IL10

TGF-beta

Front 39

origin of alloantigen-specific TRegs

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by positive selection in thymus

by clonal expansionin the periphery of naturally occurring TRegs that cross react with alloantigens

conversion of naive or activated alloantigen specific peripheral T cells to a regulatory phenotype

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result of stim of TCR with CRLA4

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enhances suppressive activity of TReg

Front 41

result of stim of TCR with GITR, CD28, IL2R

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inhibits Treg activity

Front 42

effector mech of TReg

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modify fxn of CD4 and 8 cells through cell contact or indirectly through APCs

Front 43

S1P

Back 43

stimulates T cell migration from the lymph node to the sinus in a concentration dependent manner

is required for T cell migration from the thymus

Front 44

stimulates T cell movement to where there is a high concentration of it

is required for T cell migration from the thymus

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S1P

Front 45

how are T cells retained in the lymph node

Back 45

high concentrations of S1P may reduce S1P1 (S1P receptor0 on T cells and block chemotaxis of T cells in response to S1P

Front 46

graft vs host disease

Back 46

After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of cytokines, including TNF alpha and interferon-gamma (IFNg)

Front 47

3 phases of physiology of G vs H disease

Back 47

1. host apc activation
2. donor T cell activation
3. cellular and inflammatory effectors