Transplantation Immunology

Question 1

● Lifesaving treatment for end- stage organ failure,
cancers, autoimmune diseases, immune deficiencies, and a variety of other diseases.

Answer 1

Transplantation

Question 2

DEFINITION
 The transfer of cells or tissues from one individual to another or from one site
to another in the same individual.

Answer 2

TRANSPLANTATION

Question 3

TRANSPLANTATION
DEFINITION
 The _______between the donor and host is the most important factor that determines whether a transplant will be successful.

Answer 3

genetic match

Question 4

 The closer the genetic match between
the donor and recipient in terms of_______, the_____ the risk of rejection.

 However, even with a good HLA match, rejection can occur due to________, which are encoded by genes outside the
MHC.

Answer 4

HLA types, lower

minor histocompatibility antigens (mHAs)

Question 5

HLA SYSTEM/MHC
• Composed of:
• Class I: (3)
Expressed on all nucleated cells
• Presents to CD8+ T cells (Cytotoxic T cells)

Class II: (3)
Expressed on antigen-presenting cells
• Presents to CD4+ T cells (Helper T cells)

Answer 5

HLA-A, HLA-B, and HLA-C

HLA-DR, HLA-DQ, and HLA-DP

Question 6

HLA SYSTEM/MHC

Short arm of chromosome 6 in MHC.
Inherited
as haplotypes from parental
chromosomes
_____HLA identical
_____HLA haploidentical
_____HLA nonidentical
_____Recombination

Answer 6

25%

50%

25%

<1%

Question 7

• these are expressed on the
surface of almost all nucleated cells and exhibit significant diversity among individuals.

Answer 7

HLA SYSTEM/MHC

HLA antigen

Question 8

• Largest immunologic barrier to successful allogeneic organ transplantation.

Answer 8

HLA SYSTEM/MHC

Question 9

• Largest immunologic barrier to successful allogeneic organ transplantation.

Answer 9

HLA SYSTEM/MHC

Question 10

(___________), meaning there are numerous possible variations or alleles for each gene.

Answer 10

Allelic polymorphism

Question 11

• Non-HLA proteins that demonstrate variation in the amino acid sequence between individuals and are able to
trigger an immune response
in a transplant recipient

Answer 11

MINOR HISTOCOMPATIBILITY
COMPLEX (mHAs)

Question 12

X-linked and Autosomal inheritance

“slower” rejection pace”

Answer 12

MINOR HISTOCOMPATIBILITY
COMPLEX (mHAs)

Question 13

CD4 or CD8 T cells recognize the variant protein in an MHC-restricted fashion and mediate the immune response.

This response is analogous to the
reaction to a microbial antigen.

Answer 13

mHAs

Question 14

• a cell surface protein that is involved in gamma or delta T-cell responses.

• Polymorphic (_____allelic variants)

Answer 14

MHC CLASS I-RELATED CHAIN A (MICA) ANTIGENS

> 50

Question 15

• Expression
Expressed on: endothelial cells, keratinocytes, fibroblasts, epithelial cells, dendritic cells, and monocytes

Answer 15

MHC CLASS I-RELATED CHAIN A (MICA) ANTIGENS

Question 16

Not expressed on: T or B lymphocytes.

Answer 16

MICA

Question 17

• The only blood group system that affects clinical transplantation.

• Can cause_______ rejection (occurs within minutes to hours)

Answer 17

ABO BLOOD GROUP ANTIGENS

hyperacute

Question 18

• ……develop in individuals lacking the corresponding blood group antigens.

As such, recipient-donor pairs must be
______to avoid this adverse outcome.

Answer 18

Anti-A or anti-B antibodies

ABO identical or compatible

Question 19

ABO Blood group

Remedy:

Answer 19

plasma exchange and intravenous immunoglobulin administration

Question 20

• (KIRs)

Answer 20

KILLER IMMUNOGLOBULIN-LIKE
RECEPTORS

Question 21

• Regulate the activity of NK lymphocytes

The KIRs contain activating and inhibitory receptors that vary in number and type on any individual NK cell.

Answer 21

• KILLER IMMUNOGLOBULIN-LIKE
RECEPTORS (KIRs)

Question 22

• Normally:
Interaction between the MHC protein and the no reaction inhibitory KIR maintains the NK cells in a quiescent state.

If an NK cell encounters a cell with absent or decreased HLA class I expression, inhibitory receptors are not engaged, and a loss of negative regulatory activity occurs, resulting in…

Answer 22

NK cell activation

Question 23

• Stem cell donors have been selected for recipients who lack a corresponding class I MHC protein for the donor’s inhibitory KIR type.

• This results in alloreactivity by NK cells that repopulate the recipient
after transplant.

These alloreactive NK cells have been shown to mediate a graft-versus-
leukemia (GVL) reaction and prevent relapse after transplantation for certain types of hematologic malignancies.

Question 24

• When a recipient receives a transplant, their immune system may recognize the donor’s HLAs as foreign, initiating an immune response that can lead to graft rejection.

Answer 24

ALLORECOGNITION

Question 25

• Types of graft: : the transfer of tissue from one area of the body to another of the same individual. : the transfer of cells or tissues between individuals of the same species who are genetically identical, for example, identical twins. : the transfer of cells or tissue between two genetically disparate individuals of the same species. Most transplants fall into this category. : the transfer of tissue between two individuals of different species.

Answer 25

• Autograft • Syngeneic graft (isograft) • Allograft • Xenograft

Question 26

ALLORECOGNITION • Two main pathways of allorecognition:

Answer 26

Direct Indirect

Question 27

• Recipient T cells directly recognize intact foreign MHC molecules on donor cells.

Answer 27

• Direct allorecognition:

Question 28

• This involves the uptake, processing, and presentation of foreign HLA proteins by the recipient's antigen-presenting cells (APCs) to recipient T cells, leading to the production of antibodies and cell-mediated responses against the graft.

Answer 28

• Indirect allorecognition:

Question 29

• The effector responses against transplanted allogeneic tissue include:

Answer 29

• Direct cytotoxicity • Delayed-type hypersensitivity responses • Antibody-mediated mechanisms

Question 30

TYPES OF TRANSPLANT REJECTION

Answer 30

HYPERACUTE REJECTION ACUTE CHRONIC

Question 31

TYPES OF TRANSPLANT REJECTION • HYPERACUTE REJECTION • Timing: • Occurs _______after vascular supply is established. • Mechanism: • Mediated by ______reacting with donor vascular endothelium. • Target antigens: ***ABO, HLA, and specific endothelial antigens.*** • Causes of Preformed Antibodies: (3) • Pathophysiology: Antibody binding activates ____ and ____ cascades • Results in (3)

Answer 31

minutes to hours preformed antibodies • Blood transfusions • Prior transplantation • Maternal exposure to paternal fetal antigens during pregnancy complement and clotting cascades. thrombus formation, ischemia, and necrosis.

Question 32

• Rare in Clinical Practice due to preventive measures: • ABO compatibility matching • Pre-transplant HLA antibody screening • Crossmatch tests to confirm the absence of donor HLA-specific antibodies

Answer 32

HYPERACUTE REJECTION

Question 33

• Accelerated Rejection

Answer 33

Hyperacute

Question 34

ACCELERATED REJECTION • Timing: Occurs over______ in patients with very low levels of donor-specific antibodies pre-transplant . • Similar Features: Involves intravascular thrombosis and necrosis, like hyperacute rejection.

Answer 34

several days

Question 35

ACUTE REJECTION Timing: Occurs_____ after transplantation.

Answer 35

days to months

Question 36

2 types of acute rejection

Answer 36

Cellular alloresponse Antibody mediated response

Question 37

Mechanism: Parenchymal and vascular injury. Cellular infiltrates: Predominantly CD8+ T cells, along with CD4+ T cells and macrophages.

Answer 37

CELLULAR ALLORESPONSE (ACR)

Question 38

Cellular alloresponse • Role of Cells: _______: Cytotoxic reactions to MHC-expressing cells. _______: Cytokine production and induction of delayed-type hypersensitivity (DTH).

Answer 38

CD8+ T cells CD4+ cells

Question 39

Mechanism: • Antibodies bind to vessel walls, activating complement. • Results in transmural necrosis and inflammation (different from thrombosis in hyperacute rejection).

Answer 39

ANTIBODY-MEDIATED RESPONSE (AMR)

Question 40

• Diagnostic Criteria: Histological findings characteristic of AR. C4d deposition in peritubular capillaries. Detection of donor-specific HLA antibodies.

Answer 40

Antibody mediated response

Question 41

Months or Years • ***Progressive graft arteriosclerosis*** with fibrosis, scarring, and narrowing of vessel lumen due to smooth muscle proliferation. • Leading cause of ***graft loss*** after the first year post-transplant; difficult to treat.

Answer 41

CHRONIC REJECTION

Question 42

• Immunologic Component: • Delayed-type hypersensitivity to foreign HLA proteins. • This reaction is driven by the indirect pathway of allorecognition

Answer 42

Chronic rejection

Question 43

Cytokine and Growth Factor Effects: • Secreted by endothelial cells, smooth muscle cells, and macrophages activated by IFN-y. Stimulate smooth muscle cell accumulation in graft vasculature.

Answer 43

Chronic rejection

Question 44

• Immune response by graft lymphoid cells against the host's histocompatibility antigens.

Answer 44

GRAFT-VERSUS-HOST DISEASE (GVHD)

Question 45

GRAFT-VERSUS-HOST DISEASE (GVHD) • Common Transplants Involved:

Answer 45

• Hematopoietic stem cell (HSC) transplants (most common) • Lung and liver transplants (less common)

Question 46

• Donor T cells in the graft attack the host/recipient. • Targets: Host HLA proteins (mismatched transplants) or minor histocompatibility antigens (mHAs) (matched transplants).

Answer 46

GVHD

Question 47

• Beneficial Effects of Donor T Cells:

Answer 47

• Promote engraftment and immunity reconstitution. • Mediate graft-versus-leukemia (GVL) effect.

Question 48

• Acute GVHD • Timing: Occurs within the first____ days post-transplant. • Affected Organs: Skin, gastrointestinal tract, liver.

Answer 48

100

Question 49

• Pathophysiology: • Cytokine release due to ***donor cell activation by mismatched MHC proteins.*** • Tissue destruction via ***infiltration of donor T cells.*** • Risk Factors: • Donor-recipient match status and other clinical variables.

Answer 49

Acute GVHD

Question 50

• Chronic GVHD • Timing: Beyond____ days post-transplant. • Characteristics: Resembles______ • Affected Areas: Skin, eyes, mouth, and mucosal surfaces.

Answer 50

100 autoimmune disease.