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Immuno-Sero LEC > Transplantation Immunology > Flashcards

Transplantation Immunology Flashcards

1
Q

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

A

Transplantation

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2
Q

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

A

TRANSPLANTATION

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3
Q

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

A

genetic match

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4
Q

 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.

A

HLA types, lower

minor histocompatibility antigens (mHAs)

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5
Q

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)

A

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

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

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6
Q

HLA SYSTEM/MHC

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

A

25%

50%

25%

<1%

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7
Q

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

A

HLA SYSTEM/MHC

HLA antigen

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8
Q

• Largest immunologic barrier to successful allogeneic organ transplantation.

A

HLA SYSTEM/MHC

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9
Q

• Largest immunologic barrier to successful allogeneic organ transplantation.

A

HLA SYSTEM/MHC

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10
Q

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

A

Allelic polymorphism

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11
Q

• 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

A

MINOR HISTOCOMPATIBILITY
COMPLEX (mHAs)

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12
Q

X-linked and Autosomal inheritance

“slower” rejection pace”

A

MINOR HISTOCOMPATIBILITY
COMPLEX (mHAs)

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13
Q

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.

A

mHAs

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14
Q

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

• Polymorphic (_____allelic variants)

A

MHC CLASS I-RELATED CHAIN A (MICA) ANTIGENS

> 50

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15
Q

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

A

MHC CLASS I-RELATED CHAIN A (MICA) ANTIGENS

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16
Q

Not expressed on: T or B lymphocytes.

A

MICA

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17
Q

• The only blood group system that affects clinical transplantation.

• Can cause_______ rejection (occurs within minutes to hours)

A

ABO BLOOD GROUP ANTIGENS

hyperacute

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18
Q

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

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

A

Anti-A or anti-B antibodies

ABO identical or compatible

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19
Q

ABO Blood group

Remedy:

A

plasma exchange and intravenous immunoglobulin administration

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20
Q

• (KIRs)

A

KILLER IMMUNOGLOBULIN-LIKE
RECEPTORS

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21
Q

• Regulate the activity of NK lymphocytes

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

A

• KILLER IMMUNOGLOBULIN-LIKE
RECEPTORS (KIRs)

22
Q

• 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…

A

NK cell activation

23
Q

• 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.

A
24
Q

• 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.

A

ALLORECOGNITION

25
Q

• 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.

A

• Autograft

• Syngeneic graft (isograft)

• Allograft

• Xenograft

26
Q

ALLORECOGNITION
• Two main pathways of allorecognition:

A

Direct
Indirect

27
Q

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

A

• Direct allorecognition:

28
Q

• 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.

A

• Indirect allorecognition:

29
Q

• The effector responses against transplanted allogeneic tissue include:

A

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

30
Q

TYPES OF TRANSPLANT REJECTION

A

HYPERACUTE REJECTION
ACUTE
CHRONIC

31
Q

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)

A

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.

32
Q

• 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

A

HYPERACUTE REJECTION

33
Q

• Accelerated Rejection

A

Hyperacute

34
Q

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.

A

several days

35
Q

ACUTE REJECTION
Timing: Occurs_____ after transplantation.

A

days to months

36
Q

2 types of acute rejection

A

Cellular alloresponse

Antibody mediated response

37
Q

Mechanism:

Parenchymal and vascular injury.

Cellular infiltrates: Predominantly CD8+ T cells, along with CD4+ T cells and
macrophages.

A

CELLULAR ALLORESPONSE (ACR)

38
Q

Cellular alloresponse

• Role of Cells:
_______: Cytotoxic reactions to MHC-expressing cells.

_______: Cytokine production and induction of delayed-type
hypersensitivity (DTH).

A

CD8+ T cells

CD4+ cells

39
Q

Mechanism:
• Antibodies bind to vessel walls, activating complement.

• Results in transmural necrosis and inflammation (different from thrombosis in hyperacute rejection).

A

ANTIBODY-MEDIATED RESPONSE (AMR)

40
Q

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

A

Antibody mediated response

41
Q

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.

A

CHRONIC REJECTION

42
Q

• Immunologic Component:

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

A

Chronic rejection

43
Q

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.

A

Chronic rejection

44
Q

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

A

GRAFT-VERSUS-HOST DISEASE (GVHD)

45
Q

GRAFT-VERSUS-HOST DISEASE (GVHD)

• Common Transplants Involved:

A

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

46
Q

• Donor T cells in the graft attack the host/recipient.

• Targets: Host HLA proteins (mismatched transplants) or minor histocompatibility antigens (mHAs) (matched transplants).

A

GVHD

47
Q

• Beneficial Effects of Donor T Cells:

A

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

48
Q

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

A

100

49
Q

• 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.

A

Acute GVHD

50
Q

• Chronic GVHD
• Timing: Beyond____ days post-transplant.

• Characteristics: Resembles______

• Affected Areas: Skin, eyes, mouth, and mucosal surfaces.

A

100

autoimmune disease.

Immuno-Sero LEC (30 decks)

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