Transplantation Immunology Flashcards

1
Q

Tests before kidney transplantation

A

Compatibility

  • HLA (A, B, DR)
  • ABO (blood Ag’s)

Pathogens

HIV, HepB/C, AMV, HTLV, Syph, EBV

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2
Q

Most common type of transplantation

A

allogenic

(from genetically different individuals)

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3
Q

Allogenic immune responses after transplantation are caused by ______

A

Genetic differences (MHC, ABO) between donor and recipient

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4
Q

What is a hyperacute reaction?

What two things can cause it?

A

An immediate response to either ABO or MHC expressed by endothelial cells

  1. Preexisting AB’s to A/B antigen = acute rejection
  2. Preexisting _AB’s to MHC_I or II from pregnancy, blood transfusion, or transplantation
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5
Q

What needs to be tested before blood transfusion or organ donation

A

ABO blood antigens

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6
Q

RBC’s dont express ____

They do express ______

A

Dont express MHC

Do express CHO antigens (ABO)

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7
Q

Antibodies to blood antigens A or B can cause ______ or _______.

What kind of reaction is this?

A

Complement fixation/rapid RBC clearance or hyperacute rejection

Type 2 HS reaction

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8
Q

All blood types/genotypes express __ enzyme

A

H

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9
Q

A antigen ends in ____

A

GalNAC

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10
Q

All ABO antigens are connected to _____ at its base

A

A ceramide

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11
Q

Blood types are inherited from…

A

both parents

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12
Q

Minor blood group antigens

The most important one is ____, due to…

Other minor blood group antigens such as ___, __, and ___ are less _____

A

Rhesus: C, D, E

RhD is morst important because it has high immunogenicity

Kell, Duffy, MN are less immunogenic

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13
Q

TImeframe for acute rejection

A

Occurs within WEEKS

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14
Q

Acute rejection caused by what?

This is similar to what kind of reaction?

How can this be prevented?

A

effector CD4+ TH1 cells or CD8 Tcells responding to HLA differences between donor and recipient

Like a Type 4 HS reaction

Immunosuppressive drugs or anti-T-cell antibodies

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15
Q

Accelerated acute rejection (AAR) ocurs within…

Mediated by what?

A

days

mediated by sensitized memory T cells from previous exposure or grafts

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16
Q

What happens during acute rejection?

A

Alloreactive CD8 T cell responds to antigen on parenchymal cells = damage to parenchymal cell and interstitial inflammation

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17
Q

Allorecognition occurs when (2 ways)

A
  1. TCR recognizes an allogenic MHC whose structure resembles the MHC-foreign epitope complex
  2. TCR recognizes structure formed from allogenic MHC + bound peptide
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18
Q

Direct vs Indirect allorecognition

A

Direct = CD4 and CD8 bind directly to donor DC

Indirect = Donor DC death produces membrane vesicles that contain the allogenic complexes –> get internalized and presented by recipients DC to CD4/CD8 cells

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19
Q

After transplantation, __________ migrate to the recipient’s _____ to activate T cells (which mediate rejection)

A

Donor’s dendritic cells

Spleen

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20
Q

What is a Mixed lymphocyte reaction test?

It measures ____ and ______

How is it read?

A

Co-culture of donor + recipient blood cells, measures T-Cell proliferation and T-cell cytotoxicity

More proliferation = More mismatch

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21
Q

Chronic rejection occurs ______ after transplantation

_______ occurs, leading to ______

A

Months to years after transplantation

Thickening of vessel wall leadds to ischemia

22
Q

Which HLA’s are most important in matching kidney transplant?

A

A, B, DR

23
Q

______ that differ in amino acid sequences give rise to ________________ between donor and recipient

A

Polymorphic self proteins

minor histocompatibility antigen differences

24
Q

2 types of alloreactions

A
  1. Transplant rejection = recipient’s T cells attack transplant
  2. GVHD = When hematopoietic cells are transplanted the T cells in the transplant attack the recipient’s tissues (in Soviet Russia, graft attacks you!)

*there is also Graft-versus-Leukemia against leukemic or tumor cells (a type of GVHD)

25
Q

Three conditions for GVHD to occur

A
  1. Graft must have immunocompetent T cells
  2. There must be an MHC mismatch
  3. The recipient must not be capable of rejecting the graft
26
Q
  • During GVHD, T cells circulate in blood to ________
  • Alloreactive cells interact with _______ and proliferate
  • _______ and ______ enter tissues inflamed by the conditioning regimen and cause further tissue damage
A

Secondary lymphoid tissues

Dendritic Cells

Effector CD4 and CD8 T-cells

27
Q

Pros and cons of BMT

A
  • Pros
    • Can cure lots of diseases
    • Lots of donors
    • Simple procedure (marrow from iliac crests… local anesthesia, 30 minutes)
  • Cons
    • GVHD
    • Non-functional T cells due to MHC mismatch
    • Failed reconstitution (graft failure)
28
Q

Alternative stem cell sources to minimize GVHD

A
  • Autologous marrow (obtained before radiation)
  • Umbilical cord blood cells (lots of CD34+ hematopoietic cells)
  • Isolated stem cells free of T cells
29
Q

Donor cells kill recipient tumor cells based on _______

A

MHC1 differences

30
Q

Haploidentical transplant in which the recipient has only one of two ___________ of the donor.

Donor hematopoietic cells inhibit _____

Recipient hematopoietic and leukemia cells inhibit ______

A

inhibitory HLA-C

Donor = inhibit ALL donor NK cells

Recipient = inhibits only SOME donor NK cells

31
Q

GVHD has ____ stages/grades

These are based on what tissues?

A

4 stages

Skin, Liver, and GI tract

32
Q

____ are the xenoplantation donor of choice

3 problems with this procedure?

Solutions?

A

Pigs

Problems:

  1. humans have antibodies to pig endothelial CHO
  2. human complement attacks pig cells
  3. Zoonoses

Solutions

  • Transgenic pigs expressing DAF
  • Transgenic pigs that dont express the reactive antigens
  • Germ free pigs
33
Q

What is the advantage of xenotransplantation?

A

MHC molecules differ between species = human T cells dont recognize

Therefore T cell response is mild

34
Q

___________ make allogenic transplantation possible, and also treat __________

Four Examples?

A

Immunosuppressants, Autoimmune diseases

  • Corticosteroids
  • anti-lymphocyte proliferation drugs
  • microbial immunosuppressives
  • Immunosuppressive antibodies
35
Q

Short and long term sides from immunosuppressive drugs

A

Short = susceptibility to infection

Long = higher incidence of cancer

36
Q

Immunosuppressive targets for:

  • Belatacept
  • Alemtuzumab
  • rATG
  • Basiliximab
  • Anti-CD3 mAB
A

Belatacept = CD28
Alemtuzumab = CD52
rATG= immunodepletion
Basiliximab = IL-2
Anti-CD3 mAB = TCR/CD3 complex

37
Q

Target for:

  • Tacrolimus, Cyclosporin
  • Methotrexate, Mycophenolate, Cyclophosphamide, Azathioprine
A
  • Ca–> calcineurin
  • DNA replication
38
Q

Anti-CD52 is efficient at…

A

depleting leukocytes before organ transplantation

39
Q

Prednisolone mechanism

Side effects?

A

induces IkB-alpha = inhibits NFkb activation

Side effects = cortisol sides

40
Q

Corticosteroid effects (5)

A
  • Reduces cytokine-mediated inflammation
  • Reduces NO
  • Reduces PG’s/LT’s
  • Reduces emigration of leukocytes from vessels
  • Induces apoptosis in lymphocytes and eosinophils
41
Q

Annexin/Lipocortins suppress

A

PLA2

42
Q

Cyclosporine A derived from _____

Targets ____

Blocks _____

A

a cyclic decapeptide from soil fungus

Targets calcineurin

blocks NFAT activation

43
Q

Fk506 (a.k.a.___) definition

Targets ____

blocks _____

A

macrolide from soil actinomycete

Targets calcineurin

blocks NFAT activation

44
Q

Rapamycin definition

Blocks ___, which is required for ______

A

macrolide from soil bacterium

Blocks mTOR, required for cell proliferation (inhibits IL-2 signaling)

45
Q

Mechanism of Anti-CD3 monoclonal antibody (2 effects)

it is used to treat what?

A
  • depletes T cells
  • Promotes phagocytosis or complement-mediated lysis

*used to treat acute rejection

46
Q

Calcineurin is a ________ that activates ______ and is inhibited by _____/_____

A

ST kinase

activates NFAT

inhibited by CsA or tacrolimus (FKBP)

47
Q

calcineurin is a ______ protein, required for _______

A

calcium-binding protein

required for T, B, and granulocyte activation

48
Q

effect of CsA or FK506 in granulocytes

A

reduced calcium-dependent exocytosis of granules

49
Q

Nonspecific cytotoxic drugs target _______ cells

Examples? (with mechanisms)

A

dividing cells

Azathioprine = inhibits DNA replication (all dividing cells)

Cyclophosphamide = cross links DNA (bladder damage sides)

Methotrexate = Inhibit Thymidine synthesis (prevents DNA rep)

50
Q

Uses and limitations for antibodies specific to human T cells

A

Used to deplete T cells or to suppress their functions

Limitation = the non-human antibodies can induce formation of antibodies to the anti-Tcell antibodies (yo dawg)

This reduces the effectiveness of the anti-Tcell Ab’s