Blood And Lymph - Dickinson - Transplant Immunology

Front 1

Define Autograft (ie Autologous)

Back 1

Pts own tissue

Front 2

Define Isograft (ie Synergeneic)

Back 2

Graft from Identical genetic individuals (I=Isograft)

Front 3

Define Allograft

Back 3

A = Another Person (vs. Auto = pts own tissue)

Graft from another person

Front 4

Define Xenograft

Back 4

Graft From Animal of dif. species (X=diff. species)

Front 5

Histocompatibility

Back 5

Property of having the same or mostly the same alleles ie Major histocompatibility complexes (2 in 10,000 people will be identical at MHC 1 and MHC 2, 1 in 4 siblings will have identical)

Front 6

Where are MHC 1 and 2 expressed?

Back 6

most tissues

Front 7

Define Alloantigen

Back 7

Antigen thats part of our self-recognition ie major histocompatibility antigen

Front 8

Define minor histocompatibility antigen

Back 8

Receptors on cell surface of donated organs that are known to make immunological response...but less of a problem than major histocompatibility

Front 9

Define graft rejection

Back 9

MHC alleles recognized as foreign by recipient's immune system

Front 10

What are the 3 classes of transplant rejection?

Back 10

Tissue Solid Organ, Bone Marrow

Front 11

Whats the most common transplant

Back 11

Blood

Front 12

T/F: 45 y/o pt is undergoing a corneal transplant for diabetes-related issues. Do you need to give them immunosuppressive drugs?

Back 12

NO, corneal transplants don't need ummunosuppressive drugs

Front 13

Whats the difference between solid organ transplant disease and Graft vs host disease?

Back 13

solid organ transplant disease = differences in HLA I and HLA II (human leukocyte antigens I and II) = MHC class I and II. Recipient's T cells attack transplant.

Graft vs host diease = Bone Marrow/stem cell transplant = T cells IN TRANSPLANTED MATERIAL ATTACK RECIPIENT tissues

Front 14

Whats the role of B cells role in transplant rejection?

Back 14

Some plasma cells become established in bone marrow - they proliferate and become long-term Ab factories

Donor-specific Abs play a role in acute rejection

Front 15

What are the most important things to type for to avoid rejection?

Back 15

HLA-A
HLA-B
HLA-DR

Front 16

Why is HMC diversity so important?

Back 16

So we can survive many diff types of insults (ex. - HIV)

Front 17

What are the 3 types of rejection?

Back 17

Acute (min-hrs), Hyperacute (days-wks), Chronic (months-yrs)

Front 18

What will you most likely NOT see in the medical setting today b/c its readily screened for?

Back 18

HYPERACUTE rejection

Front 19

What occur to some extent in nearly ALL transplants?

Back 19

ACUTE rejection - WHY we use IMMUNOSUPPRESSANTS

Front 20

How does Chronic rejection manifest?

Back 20

GRADUAL decline in graft function

Front 21

T/F: Chronic rejection is unpredictable and heterogenous in nature

Back 21

TRUE

Front 22

Whats the cause of Hyperacute rejection?

Back 22

PRE-FORMED Anti-donor Abs to ABO or MHC and complement --> graft destruction --> can't treat, lose graft

Front 23

Which type of rejection can we NOT treat?

Back 23

HYPERACUTE. Abs already formed

Front 24

How do we prevent a HYPERACUTE rejection?

Back 24

cross-match test ie recipient AB vs Donor cells --> see if lysis occurs

Front 25

How does Acute rejection occur?

Back 25

Donor Dendrites activated by inflamm and migrate to recipient's spleen or lymph nodes --> Here they encounter T cells

Donor dendritic MHC I and II recognized as foreign by CD8 cytotoxic T cells --> activated T cells destroy graft by releasing porphyrin and granzyme

Front 26

What do CD8 cytotoxic T cells release to destroy graft in Acute rejection?

Back 26

Granzyme and Porphyrin

Front 27

How do CD4 Helper T cells help cause damage in acute rejection?

Back 27

Activate macrophages via secreting inflamm cytokines = Type IV hypersensitivity rxn

Front 28

How do chronic rejections occur?

Back 28

Ab-complement rxn in graft vasculature --> dec. blood to graft --> ischemia

Front 29

What enters the tissue of grafts from chronic rejections, leading to damage?

Back 29

immune effectors

Front 30

Which is expressed on vascular endothelium, HMC I or MHC II?

Back 30

MHC I

Front 31

How do Abs mediate the damage seen in chronic rejection?

Back 31

Recruit inflamm cells
Activate Complement
Mediate Ab-dependent cellular toxicity

Front 32

How are T cells activated in Acute vs Chronic rejection?

Back 32

Acute = DIRECT Chronic - INDIRECT

In Acute, the graft itself has antigen presenting cells like dendrites that present SELF-peptide to recipient T cells.

In Chronic, Allopeptide (from the graft) is presented to CD4 T cells by the recipient's OWN dendritic cells, NOT the dendritic cells of the graft.

Front 33

Allopeptide is presented to a CD4 T cell via MHC II. Is this Acute or chronic rejection

Back 33

CHRONIC

Front 34

Self peptide from a graft is presented to CD4 T cells via MHC II. Is this acute or chronic rejection?

Back 34

ACUTE

Front 35

Describe the Cross-match test...

Back 35

Donor B cells and Donor T cells in blood are mixed with Recipient Blood, Complement and Dye.

If the Recipient has Abs to Anything present on the donor's T CELLS (not B cells...) the sample will Lyse and this is considered a POSITIVE rxn and the samples are NOT compatible.

Front 36

In which tissue is transplantation most sensitive to HLA display?

Back 36

Bone Marrow

Front 37

What are some sources of stem cells?

Back 37

bone marrow, cord blood, peripheral blood (=normal blood)

Front 38

We can see rejection of bone marrow in all pts EXCEPT those who...? (ie what pts will NOT develop GVHD, graft vs host disease?)

Back 38

Have Immuno-compromised disease (= they can't mount immune response to bone marrow trancplant)

SCID, Agammaglobulinemia, Hyper IgM Syndrome, Selective IgA deficiency etc.

Front 39

What diseases can be treated with bone marrow transplant?

Back 39

Primary immunodeficiencies
Some Leukemias
Aplastic Anemia
Autoimmune disease

Front 40

How does GVHD occur?

Back 40

T cells in Transplanted bone marrow are activated against recipient MHC

Recipient MHC class I recognized by sensitized CTLS = killing of mucosal and epi cells

Front 41

How does GVHD manifest?

Back 41

NOTE: Skin, Liver, GI - major sites

Skin rash
Profuse watery diarrhea
Abnormal Liver Function Test

Front 42

What are the MAJOR sites of reaction seen in GVHD? WHY?

Back 42

Skin, Liver, GI

= they express higher levels of MHC than other tissues

Front 43

What diseases is stem cell transplant currative?

Back 43

Diseases where the recipient's are immunodeficient:

Primary Immunodeficiency
Some Leukemias
Aplastic Anemia
Autommune disease

(Exs = SCID, Agammaglobulinemia, Hyper IgM Syndrome, Wiskott-Aldrich syndrome, Selective IgA deficiency)

Front 44

Whats the advantage of using CORD BLOOD t oget stem cells from vs. Bone marrow or peripheral blood?

Back 44

There are NO mature T cells in cord blood = less chance of GVHD

Front 45

Whats the limitation of using cord blood as a source of stem cells?

Back 45

There's usually not ENOUGH stem cells.

Front 46

WHY does a corneal transplant NOT require immunosuppressive drugs?

Back 46

Gradt antigens don't access Lymph vessels or Nodes meaning they can't sensitize recipient's lymphocytes

Front 47

What drives immune reactions between T cells and MHC molecules?

Back 47

If T cell doesn't recognize MHC, it will attack it

Front 48

If you see MHC-A, MHC-B MHC-C, you KNOW its what type of MHC?

Back 48

MCH I

Front 49

If you see MHC-DM, MHC-DQ, MHC-DR, you KNOW its what type of MHC?

Back 49

MHC II

Front 50

THE MAJOR MHCs that predict rejection?

Back 50

MHC-A, MHC-B, MHC-DR

Front 51

Your MALE pt needs a transplant. RATE family members in order of most likely to contain compatible MHC molecules

Back 51

1. gentically identical sibling (=have SAME MHC)
2. Brother (ie same sex sibling)
3. Sister
4. dad (ie same sex)
5. mom

Front 52

Which are better, younger or older donors? same race or does it matter?

Back 52

YOUNGer, same race

Front 53

Whats an example of a NATURAL situation that can lead to production of anti-HLA?

Back 53

pregnancy (ie fetus expressed paternal HLA thats not part of mother's HLA type) --> Anti-HLA Abs develop

Front 54

Difference between CD8 cytotoxic T cells and CD4 Helper T cells in Acute rejection?

Back 54

CD8 cytotoxic T cells = kill graft by releasing granzyme + porforin

CD4 Helper T cells = Activate macrophages by secreting inflamm cytokines


These mediate BOTH acute and CHRONIC rejection, they are just INITIATED by dif. processes

Front 55

In Chronic rejection (ie INDIRECT pathway), Recipient Dendritic cells do what? 1. present graft peptide t oCD8 T cells in the context of MHC I OR 2. present graft peptide to CD4 T cells in context of MHC II?

Back 55

present graft peptide to CD4 T cells in context of MHC II?


Vs. Acute rejection = DIRECT pathway = recipient dendritic cells present graft peptide to CH8 via MHC II OR CD4 via MHC I

Front 56

Which, chronic or acute involves ONLY dedritic cells presenting to CD4 T cell via MHC II?

Back 56

CHRONIC

Front 57

Whats the treatment for GVHD disease?

Back 57

Give something that reduces the T cells that lead to the reaction ie T-cell depleting agent