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MICR2221 - Medical Immunology > L10 - Transplantation > Flashcards

L10 - Transplantation Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the 2 important barriers against transplants?

A

Rejection

tissue availability (shortage)

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2
Q

What is the most simple transplant used in clinical practice?

A

blood transfusion - ABO system

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3
Q

What does allele A of the blood do?

A

modifies H into A

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4
Q

What does allele B of the blood do?

A

modifies H into B

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5
Q

What does Allele O of the blood do?

A

NON-FUNCTIONAL enzyme

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6
Q

What do humans produce IgM against blood of?

A

IgM against blood group carbohydrate YOU LACK!

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7
Q

What is an autograft?

A

graft of tissue from one site to another - SAME INDIVIDUAL

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8
Q

What is an allograft?

A

transplant from unrelated individual of same species

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9
Q

What is a Xenograft?

A

transplant using tissue of different species

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10
Q

What is acute rejection?

A

initial success
NO immunosuppression
fail after 10-14 days

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11
Q

What is chronic rejection?

A

effective immunosuppression
last months/years
degraded

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12
Q

What is hyperacute rejection?

A

Xenographs

rejected within HOURS

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13
Q

What molecule is a major barrier to transplantation?

A

MHC

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14
Q

Why do animals given a 2nd allograft reject it quicker than 1st?

A

primed rejection

memory-type response

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15
Q

What is acute rejection mediated by?

A

MHC and T cells

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16
Q

Are Allografts put onto nude mice, lacking T cells, rejected?

A

NO

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17
Q

What are alloantigens?

A

antigens that differ between members of same species

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18
Q

What are the most polymorphic proteins in the human pop?

A

MHC - diversity between donor and recip

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19
Q

What is polymorphism for MHC?

A

for single gene

e.g. allele from father and mother - codominant

LOOK AT SLIDES IF CONFUSED

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20
Q

What is polygeny for MHC?

A

for (3) different genes

COMBINED WITH 2 ALLELES FROM POLYMORPHISM = 6 DIFF MHC CLASS I

LOOK AT SLIDES

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21
Q

What is the other loci that contributes to graft rejection?

A

Minor Histocompatibility antigens

Y-chromosome encoded, any polymorphic protein

22
Q

How was the other loci than MHC found?

A

mice with identical MHC but different strains had a longer rejection

23
Q

What are the 2 main pathways for how donor MHC is recognised as an alloantigen?

A

DIRECT ALLORECOGNITION - APCs, T-cells,

INDIRECT ALLORECOGNITION - T-helper cells activate macrophages

24
Q

What is the 3rd mechanism of allorecognition?

A

Semi-direct - similar to indirect

transfer of donor MHC to recipient APC

25
Q

What occurs during direct allorecognition?

A

APC migrate out of graft into lymph nodes

engage with T-cells

TCR recognises allo-MHC/peptide

host effector T-cells attack graft

donor DC die

26
Q

What is another way to get rejection of graft?

A

if you deplete donor DC from the graft

27
Q

What occurs during indirect allorecognition?

A

Allogenic molecules processed by recipient DCs

presented to T cells

T-helper cells activate macrophage (presenting graft peptides)

inflammation, tissue damage - induce ALLOANTIBODIES

28
Q

What signals to T-cells provide to macrophages?

A

IFN-y
respiratory burst
cytokine production

29
Q

How do CD8 cells cause tissue damage?

A

attack graft directly

30
Q

How do CD4 cells cause tissue damage?

A

help B-cells make anti-graft antibodies against graft

31
Q

How do antibodies bound to the graft lead to destruction?

A

via complement
via ADCC

= antigen presentation

32
Q

What is thymic education?

A

T-cells learn self from non-self

33
Q

How can Allo-MHC-peptide complex bind efficiently to some TCRs?

A

similar net contacts between TCR and MHC-peptide

activation

34
Q

What are the initial and current focuses for transplantation?

A

initial - MHC matching, HLA-typing

current: immunosuppressive drugs

35
Q

What do immunosuppressive drugs target?

A

T-cell activation steps

deplete grafts of immune cells

36
Q

Downside of immunosuppressive drugs?

A

ALL transplants will still have some degree of chronic rejection

susceptible to infection

37
Q

What is the ‘future’ of transplantation?

A

xenotransplantation

38
Q

What are immunological problems with pig xenotransplantation

A

Hyperacute rejection

different carb structures

a-Gal epitope added via UDP–Gal : a1,3GT

PSEUDOGENE IN HUMANS

anti-a-Gal antibodies

pig organs rapidly coated = complement-mediated destruction

39
Q

Why do humans produce anti-a-Gal antibodies?

A

antigen carried by gut bacteria

40
Q

can pigs be gen mod to minimise hyperacute rejection?

A

try to express human complement regulators

inactivate a1,3GT

disrupt endogenous MHC I/II expression

add genes for negative regulators of immunity

extensive immunosuppressants

41
Q

What is another aspect to consider when using pig organs?

A

has to function correctly too

genome engineering tools - CRISPR-Cas9

42
Q

What is an animal chimera?

A

single organisms composed of two or more different populations of genetically distinct cells

43
Q

How can a diabetic mouse be treated (animal chimera)?

A

mouse stem cells into rat embryo

mouse pancreas inside rat

pancreatic islets transferred to mouse - also includes rat tissue = immunosuppressants required

after a while - mouse-derived vessels go through pancreas

44
Q

What are issues with xenotransplantation beyond immunological rejection?

A

transfer infectious agents from donor

ethical considerations

45
Q

What is HSC transplantation?

A

recipient immune system remove to allow repopulation with donor-derived HSC

recipient is allogenic to donor HSC and donor-derived immune system

46
Q

What disease occurs from HSC transplantation?

A

graft v host disease (GVHD)

47
Q

how can the allo-reaction in HSC transplantation be beneficial?

A

Graft v leukemia (GVL)

48
Q

What is the most common allograft?

A

foetus is half mother, half father

50% genes have MHC from father

HEMI-ALLOGRAFT

REPEATED exposure if have more children

49
Q

How is fetomaternal tolerance ahcieved?

A

does NOT express MHC II

very low MHC I

specialised MHC I = HLA-G : INHIBITS NK CELLS

factors suppress effector T-cells

promote inhibtory Treg

uterine tissue - chemokine limit T-cell attraction

50
Q

How can fetomaternal tolerance help transplants?

A

understand tolerance mechanisms - apply to solid organs

MICR2221 - Medical Immunology (16 decks)

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