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Question 1

I just performed an Orthotopic transplantation. What did I do?

Answer 1

You placed a graft in the same anatomical location

Question 2

My boss is mad at me because I did a heterotopic transplantation of a heart. Why?

Answer 2

You placed the heart (graft) into a different anatomical location

Question 3

What kind of fucking transplant is this?

Mouse to chicken

Answer 3

This is Xenogeneic transplant

Question 4

What kind of fucking transplant is this?

Between me and kiki (identical twins)

Answer 4

This is Syngeneic transplant

Question 5

What kind of fucking transplant is this?

Me to the realest fella I know (myself)

Answer 5

This is autologous transplant

Question 6

What kind of fucking transplant is this?

Me to another person

Answer 6

This is Allogeneic transplant

Question 7

Alloreactive are a special type of lymphocytes created to combat alloantigens. True or false?

Answer 7

False. They are normal lymphocytes. The “allo” (hi!) part comes from them reacting to alloantigens, which are antigens recognized as foreign in allografts

Question 8

There is no functional difference between alloantigens and xenoantigens. True or false?

Answer 8

True, the only thing that changes is the type of graft performed.

Question 9

An allograft can be rejected by memory or by lymphocytes. True or false?

Answer 9

True

Question 10

Grafts are rejected if they express an MHC type that is not expressed by the recipient, which is why children can usually give to parents but parents can’t give to children. True or false?

Answer 10

False. The first part is right, but its parents who can give to children and children who can’t give to parents.

Question 11

What are the major players when it comes to transplant rejection?

NOT CELL TYPES

Answer 11

It’s the MHC, the blood group antigens and mHC

Question 12

Blood-related transplant rejection is mediated by T lymphocytes. True or false?

Answer 12

False. It’s by antibodies.

Question 13

I just made an MHC-identical graft, but there was rejection. The blood type was the same. What happened?

Answer 13

There were problems with the mHC peptides.

Question 14

A graft with mismatched mHC is rejected as fast as a graft with mismatched MHC. True or false?

Answer 14

False. mHC gets rejected slowly.

Question 15

If donor and recipient are HLA-identical, how can a graft be rejected?

Answer 15

Because mHC antigens can differ due to genetic polymorphisms

Question 16

Give an example of an mHC antigen

Answer 16

Any antigen that is present in the Y chromosome is not tolerated in women.

Question 17

Explain the two ways a T cell can recognize an alloantigen

Answer 17

1. Direct alloantigen recognition
   A T cell binds directly to an intact allogeneic MHC molecule on an APC belonging to the donor,
2. Indirect alloantigen presentation
   An APC from the recipient picks up and processes an MHC molecule from the graft and present it to the T cell.

Question 18

In direct allorecognition, the T cell recognizes not the peptide the donor APC’s MHC is holding, but rather, the intact donor MHC. True or false?

Answer 18

True

Question 19

A T cell selected during development to weakly recognize self-MHC can recognize a self-MHC + foreign peptide complex very strongly. True or false?

Answer 19

True

Question 20

A T-cell can recognize a foreign MHC-antigen complex as being a “SELF” MHC-antigen complex and treat it as if it were a normal/recipient MHC. True or false?

Answer 20

True

Question 21

It’s impossible for a T-cell to recognize a structure formed by both an allogeneic MHC molecule and the bound peptide; it will always interpret it as “MHC + antigen”. True or false?

Answer 21

False. Yes it can. (Slide 413)

Question 22

What is the purpose of Mixed lymphocyte reaction?

Answer 22

See if T cells will reject a graft

Question 23

Explain in one sentence a mixed lymphocyte reaction

Answer 23

Extract mononuclear cells from two donors, put them in a petri dish, see if the Donor X’s lymphocytes kill the Donor Y’s APCs.

Question 24

Explain the three types of allograft rejection.

Answer 24

Hyperacute:
Right after a transplanted organ is connected to the patient’s blood vessels (within minutes to hours), the blood supply to the graft gets blocked by clots since the recipient somehow already had antibodies for the donor’s endothelial antigens.

Acute:
Alloreactive T cells and antibodies attack the graft’s tissues and blood vessels.

Chronic:
Repeated attacks to the graft with alloreactive T cells and cytokines, which then repair the injuries with fibrosis.

Question 25

Whats the difference between acute and chronic rejection?

Answer 25

An acute rejection is like a battle against the graft; it features T cells and antibodies, but can be suppressed if you "inhibit the army": A chronic rejection features T cells and cytokines, is much slower and gradual, and features other mechanisms besides just flat out attacking the tissue (for example, scarring)

Question 26

How do clots form in hyperacute rejection?

Answer 26

Antibodies that react to the foreign MHC/blood group antigens trigger the complement system, which causes the influx of neutrophils and inflammation, which inevitably leads to clot formations.

Question 27

In acute rejections, is there inflammation? If so, what causes it? If not, what inhibits it?

Answer 27

There is inflammation, and it is caused by cytokines produces by Th cells.

Question 28

The main mechanism in an acute rejection is CD4-mediated killing of graft and parenchymal and endothelial cells. True or false?

Answer 28

False. It's CD8-mediated

Question 29

Hyperacute rejection is characterized by alloantibodies binding to alloantigens (mainly MHC molecules), which leads to endothelial injury, intravascular thrombosis and eventually graft destruction. True or false.

Answer 29

False. What you're describing is Acute antibody-mediated rejection

Question 30

If a transplant fails, subsequent transplants are faster and stronger. True or false?

Answer 30

True

Question 31

Since the kidneys clear the blood of impurities, and, as such, pick up lots of dietary and microbial molecules, the body has evolved mechanisms to favor immune tolerance over activation in this organ, thus preventing constant inflammation. This has a side effect which makes kidney transplants more likely to be accepted. True or false?

Answer 31

False. Its the liver that has it. The liver is an organ that naturally processes large amounts of gut-derived antigens, including harmless dietary and microbial molecules. To avoid continuous inflammation, it has evolved mechanisms that favor immune tolerance over activation

Question 32

What organ has the highest rate of rejection? And why?

Answer 32

Its the skin, because: - It has a lot of APCs - Has a strong innate immune activation (since it's the frontline barrier against infection, it needs to be able to become inflamed easily, and, as such, this environment helps with rejecting a graft) - Skin cells have a high amount of MHC (HLA) by default, and can quickly generate more in response to inflammation - There are a lot of tissue-resident memory T-cells that are primed and ready to act - Bitch there is no "regulatory T cells to dampen the immune response"; this is the skin, you're getting jumped.

Question 33

What is graft-versus-host disease?

Answer 33

When hematopoietic stem cells are transplanted, and the T cells in the transplant attack the recipient's tissues

Question 34

Whats the difference between HLA and MHC?

Answer 34

The name. HLA are MHC but for humans.

Question 35

What are the 3 conditions that must be met for graft versus host disease to trigger?

Answer 35

1. The graft must contain immunocompetent donor T cells 2. The host must be expressing antigens not present in the donor (for example, HLA mismatches or mHC mismatches) 3. The host must be unable to eliminate the transplanted immune cells (by being, for example, immunocompromised)

Question 36

After a hematopoietic stem cell transplant, there is a period of time until the transplanted cells begin producing the same immune cells as the recipient originally had. True or false?

Answer 36

False. In a HSC graft, the HSC replaces the patient's hematopoietic system, resulting into immune reconstitution.

Question 37

After a HSC graft, immune reconstitution can be done in two ways: Thymus-____________ pathway, in which the donor HSC's give rise to new __________________, which is a very slow process, being able to take up to __________ Thymus-_______________ pathway, where __________________ expand peripherally by homeostatic proliferation and provide early cellular immunity. This is a fast process, taking _________ at most to happen.

Answer 37

Dependent naive T cells years Independent mature donor T cells weeks

Question 38

In a HSC graft onto a leukemia patient, Mature donor T cells can be considered a double edged sword. Why?

Answer 38

On one hand, they recognize mHC antigens expressed by leukemic cells and kill them. But on the other, they are also the principal mediators of graft-vs-host-disease.

Question 39

Give me the pros and cons of a T-cell repleted graft vs a T-cell depleted graft.

Answer 39

Repleted has a faster immune reconstitution, but increases the risk of severe GVHD Depleted is the opposite, meaning it has a slower immune reconstitution (which may increase early infection morbidity), but on the bright side it reduces GVHD

Question 40

Treg infusion is a high risk, high reward strategy for HSC grafts, as it allows the presence of donor T cells for reconstitution and the GVL effect, but also increases GVHD risk. True or false?

Answer 40

False. It PREVENTS GVHD

Question 41

When a patient receives a hematopoietic cell graft of a completely different HLA type from their own, the donor-derived lymphocytes do not respond to anything. True or false?

Answer 41

True

Question 42

What's the problem of a patient receiving a hematopoietic cell graft from a completely different HLA type from their own?

Answer 42

T cells formed are only trained to recognize the donor's HLA, meaning they don't interact with the recipient's HLA. As such, when an APC presents an antigen from an infection, the lymphocytes don't do anything because they don't even recognize the HLA as a place they can bind to.

Question 43

What is mixed chimerism?

Answer 43

It's when hematopoietic cells from both donor and recipient coexist.

Question 44

I want to do mixed chimerism, but I keep fucking up and killing my patients. Tell me what I'm probably doing wrong.

Answer 44

You need to engraft immune cells from the donor alongside the transplant, as this way the immune system will relearn tolerance through both central and peripheral tolerance mechanisms.

Question 45

Central tolerance is thymus-independent. True or false?

Answer 45

False. It depends on the thymus.

Question 46

How does central tolerance prevent the rejection of donor tissue?

Answer 46

Because the donor's own APCs participate in negative selection of the maturing T cells, which leads to alloreactive T cells being deleted. No alloreactive T cells, no injury.

Question 47

We know for a fact that even after thymic selection, some donor-reactive T cells persist. Why don't they lead to a massive immune attack?

Answer 47

They are controlled through Tregs, Anergy by lack of costimulatory signals, and apoptosis

Question 48

__________ tolerance is related to stable long term tolerance, while ___________ tolerance is more related to an active suppression of a graft immune attack. Why?

Answer 48

Central (because it reshapes the immune system from the ground up) Peripheral (Because it prevents the already-formed T cells from fucking up the graft)

Question 49

Trophoblasts do not express any sort of HLA, MHC (I or II) or mHC, thus preventing maternal CD8+ and CD4+ T cell activation. True or false?

Answer 49

False. They express HLA-G, which is a special type of HLA I that inhibits T cells and NK-mediated killing and induces tolerogenic DCs.

Question 50

Besides the receptors, a way the placenta has to lower immune problems is by producing tryptophan, which depletes IDO and, as a consequence, reduces maternal T cell responsiveness. True or false?

Answer 50

False. The placenta produces IDO, which depletes tryptophan, etc

Question 51

The NK cells in the decidual are poorly cytotoxic. True or false?

Answer 51

True.

Question 52

Trophoblasts produce cytokines and chemokines that suppress the development of any B and T cell. True or false?

Answer 52

False. The molecules produced by them favor the development of pTregs

Question 53

Every receptor and molecule produced by the placenta has the objective of suppressing, inhibiting or lowering the immune response and T cell development in some way. True or false?

Answer 53

False. They favor the development of pTregs.