Immuno 23 Transplants

Front 1

what is an...
1. auto
2. iso
3. allo
4. xeno

what produces the largers IR

Back 1

1. auto: persons own tissue is transplanted (least immunogenic)

2. iso: identical twins (genetically identical)

3. Allo: same species, dif genetics

4. xeno: dif species (MOST immunogenic)

Front 2

what are the 2 major types of transplant

Back 2

1. HSC (hematopitic stem cell): BM, peripheral blood, cord blood

2. Organ Transplants: can be auto, allo, or xeno even

Front 3

why would you get a HSC transplant? what about whole organ?

Back 3

HSC: blood disorders/cancers, immunodeficiencies (primary), when chemo kills your BM

Organ: organ failure, replace bad tissue, condition with recurrence

Front 4

whats a foerign AG on the surface of transplanted tissues? what are the immune cells that attack them called

Back 4

AlloAG: the foerign AG on the surface of transplanted tissues

Alloreactive T/B: host cells that kill AlloAG

Front 5

what is an alloreactive T or B cells

Back 5

alloreactive Ig

T and B that kill alloAG (AlloAG are foerign proteins that are found on transplanted tissues)

Front 6

what is the major limitation to transplants

Back 6

alloreactive T and B cells

Front 7

what are the Major Histocompatibleibity responses in transplant/ minor?

Back 7

major: MhC, elicits STRONG IR

Minor: various other molecules other than MHC, weaker IR

Front 8

what is responsible for strong IR that cause ALLOgraft rejections

Back 8

MHC mismatch

Front 9

what is a haplotype

Back 9

the set of MHC you have

each person has 2 sets

Front 10

familily who has the closest MHC haplotypes

Back 10

twins! they will have hte same (identical)

siblings are 25% liekly to have the same. parents will be 50% identical

Front 11

we know an alloAG is an AG onthe surface of hte transplanted tissues, commonyl what is this

Back 11

often is MCH, can be others as well

Front 12

what are the 2 ways a host's T cells recognize MHC AlloAG

Back 12

1. Indirect Presentation: self APC present graft peptides (MCH if mismatched, nad minor histocompatibility complexes)

2. Direct: Donors APC present peptide in allogenic MHC

Front 13

what is indirect and direct presentation of protein to activate self T cells

Back 13

Direct: graft APC resent peptide in ALLOGENIC MHC

Indirect: self APC present GRAFT peptides derived from MHC or monorHC

Front 14

whats it called when self T cells are activated bc they are presented with GRAFT MCH, what about if they have SELF APC present GRAFT peptide

Back 14

Direct: graft APC presents Graft APC

Indirect: self APC presents GRAFT derived peptide

Front 15

if foerign MCH is ised to present peptide to activate self t cells what is it called

Back 15

DIRECT recognition of allogenic MHC

there are 2 ways T cells recognize foerign MHC, (MHC elicits a super strong IR). 1 is by us presenting MHC peptides like any other normal T cell activation. The other is then the transplanted tissue uses its APC and directly presents its MHC to our T cells

Front 16

what plays a role in chronic rejection? acute

Back 16

Chronic: alloreactive Th, (HS 4 rxn)

Acute: alloreactive CTL

Front 17

what is a hyperacute rejection

Back 17

super fast, occurs in minutes to hours.

there are PRE-existing AB against the graft

Front 18

so if we have pre-existing AB to a graft what will happen? what can make us have preexisting AB

Back 18

hyperacute rejection, minutes to hours

**can be ABO mismatch, Rate

AB are already there bc...
blood transfusion
previous transplant
multiple pregnancies

Front 19

what can increase the risk of having preexisintg AB to a granf and having a hyperacute rxn

Back 19

blood transfusion
previous transplant
multiple pregnancies

Front 20

how can you prevent a hyperacute rxn

Back 20

ABO typing
crossmatching tests to determine if there are preformed AB to donor AG

Front 21

how does hyperacute rxn occue

Back 21

preformed AB to the graft

compliment is activated, PMN infiltrate.
PMN release lytic enzymes and damage endothlium
this endo damage causes clotting mechs-thrombi formation and block blood flow to graft

Front 22

what type of rejection occurs when preformed AB attack the grafts endothelium. This activates compliment and precruits PMN, the PMN then cause endo damage that initiates clotting cascades, this causes thrombi formation and blocks BF to graft

Back 22

hyperacute

Front 23

if you reject somthing in 5 hours what kind of rejectio? wht about 10days-2mo?

Back 23

hyperacute
acute

Front 24

T cells play a role in what tyoe of rejection

Back 24

Acute

anything btwn 7 days and 2 mo.

t cells respond to AlloAG and kill them. CTL KILLING IS HALMARK

Front 25

CTL killing is hallmark of what rejection? is this the only mech for this type of rejection

Back 25

acute

**CTL lyss the graft directly, OR recruit inflammation, macrophages, AB

Front 26

so we sid to reduce the odds of rejection we HLA ctype and Corss match. what is HLA typing? what rejections is it SUPER importnat for

Back 26

make sure pts have hte same 6 MHC,

BM, Kidney, SUPER important

heart and liver not as picky with MHC

Front 27

what type of rejection uccurs as the result of fibrosis and occlusion of vessels

Back 27

chrinic

Months to years (more than 2 mo, 2mo is acute)

irreversible process, slow rejection mediated by BOTH AB and CTL

Front 28

if we have chronic stim of the Immune system via AB and CTL what type of rejection can we ahve

Back 28

chronic

Months to years

Front 29

what are 2 tings that work together to aid chronic rejections

Back 29

1. Chronic Inflammation, Th1 causes fibrosis

2. SM proliforation. lymphocytes cause macrophages to release cytokines that induce GF,this narrows the vessels

both cause decreased BF, and ischemia, fibrosis, necrosis

Front 30

if we have alloAG that activate T cells. T then activate macro and hte macro then secrete cytokines that induce SM GF

Back 30

this is chronic rejection, this reduction in BV lumen diameter paired with chronic inflammation can lead to ischemia and death

**fibrosis and occlusion, CHRONIC rejection

Front 31

what is Graft vs Host disease

Back 31

when the graft has immunocompetence nad will attack the host

Front 32

is GcD diesase acute or chronic

Back 32

either

its just when DONOR T cells recognize alloAG on host cells

Front 33

what transplants are more common to see GvH disease

Back 33

BM
liver
intestines

**immunocpmpetent tissues

Front 34

how can we prevent GvH disease

Back 34

partial donor T cell depletion before transplantation

must leave SOME t cells bc mature T secrete CSF to repopulate

Front 35

what medical regime is the key to prevent long term rejection

Back 35

immunosupression (maintained)

Front 36

how can you reduce risk of chronic rejection

Back 36

hard to do

they think if you prolong development of the acute rejection you also prolong chronic rejection

Front 37

wjat is a general immunosupressive drug? wht else

Back 37

corticosteroids

predisone, methlypredisone, dexamethasone

SUPRESS inflammation, inhibit IL1, decrease PG, LT, decrease T cell Activation

Mitotic Inhibitor: inhibit synthesis of nucleis acids

Front 38

what do corticosteroids and mitotic inhibitors have to do with grafts

Back 38

they are general immunosupressents

Glucocorticoids are antiinflammatory and decress t cell activation

Mitotic inhibitors prevent nucleic acid synthesis

Front 39

what are some more specific immunosupressive therapies

Back 39

IL2 inhibitors: inhibit T cell proliforation


Polyclonal Antithymocyte AB

Monoclonal AB

Front 40

what is teh mode of T cell Activation

Donor APCs can present donor antigens to recipient T cells

Recipient APCs can present donor antigen (peptides of donor MHC) to recipient T cells

Back 40

direct

indirect

Front 41

what is the mechanism, time frame, prevention, and therapy for Hyperacute rnxs

Back 41

preexisting AB activate compliment and ADCC

minutes to hours after transplant

prevent with blood type screen for preexisting AB

No therapy

Front 42

what is the mechanism, time frame, prevention, and therapy for Acute Rejection

Back 42

B/T activation: Th1 mediated killing. B does compliment and ADCC.

7-10 days to 3 mo

Prevent with blood type screen, MHC match

Therapy: general and specific immunotherapy, induction and maintaince phases

Front 43

waht is the mechanism, time frame, prevention nad therapy for chronic rejection

Back 43

Th1 mediated inflammation. GF increase proliforation of vascular SM

occurs months to years after transplant

Prevent by matching MHC

Therapy: prevent acute can slow chronic. no formal chronic tx

Front 44

what is the mechanism, time frame, prevention and therapy for GvH disease

Back 44

mechanism is similar to acute and chronic but its when the Graft rejects the Host

time frame can vary nit is months to years after transplant

prevent by mathcihjg MHC nad partial T cell depletion of graft

general and specific immunotherapy. induction and maintanice phases