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Flashcards in Transplantation Deck (26)
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1
Q

What is allorecognition?

A
  • The ability of an organism to distinguish its own tissues from those of another
  • It manifests itself in the recognition of antigens expressed on the surface of cells of non-self origin

​​= transplant rejection

2
Q

What are the cellular processes behind allorecognition?

A
  • MHC dramatically different for each individual
  • ALLORECOGNITION
  • Random, instant activation of 10% of all CD4 and CD8 T cells in the body
  • Many are memory and effector cells already programmed to defend against pathogens
3
Q

What is the major histocompatibility complex (MHC)?

A
  • Set of cell surface proteins essential for the adaptive immune system
  • Contains large number of immune-related genes
  • MHC molecule (class I & II) binds to epitope from antigen and presents it to T-cell receptor
4
Q

How is MHC expressed?

A
  • MHC expression is co-dominant for each MHC gene
  • both sets of inherited alleles are in each cell
  • Total 14 MHC genes
5
Q

How is diversity in MHC achieved?

A
  1. An organism’s MHC repertoire is polygenic (works with other genes to have an effect)
  2. MHC expression is co-dominant (from both sets of inherited alleles);
  3. MHC gene variants are highly polymorphic - greatly varying from organism to organism within a species, many different alleles for each MHC gene
6
Q

Why is MHC diverse?

A
  • Driven by the need to be able to present as many different peptide antigens as possible (to T-cells)
  • Each different MHC allele can present a select set of peptides
  • To be same from all viruses, need a set of different MHC alleles

→ ∴ infectious diseases are driving the evolution of MHC

7
Q

List 3 mechanisms of rejection

A

Adaptive immune response

Depends on type of organ and the type of antigenic mismatch:

  1. Antibody-mediated cell killing (like type II hypersensitivity)
  2. T cell-mediated cell killing
  3. T cell-mediated inflammation (like Type IV hypersensitivity)
8
Q

What is an allogeneic transplant?

A
  • Patient receives bone marrow or peripheral blood stem cells from another person
  • Usually a sibling but can be an unrelated donor
  • Usually required following high dose whole body radiotherapy = kills bone marrow cells = loss of blood cell replacement
9
Q

What is Graft vs Host Disease? (GvHD)

A

Condition that can occur after an allogeneic transplant

  1. Allorecognition → The donated bone marrow/peripheral blood stem cells view the recipient’s body as foreign
  2. Donor’s lymphocytes become activated
  3. The transplanted lymphocytes attack the body
10
Q

What is the only way to avoid transplant rejection/GvHD?

A

Remove antigen:

The perfect MHC match of donor and recipient

11
Q

Why is it difficult to get a good MHC match?

A
  • Have to match up 7 different genes
  • And 2 different types (alleles) of each gene = 14 genes
12
Q

What are the sources of the 2 best possible MHC matches?

A
  1. Genetically identical twins = syngeneic
  2. Self = autograft
13
Q

List the 3 classes of immunosuppressant drugs which block alloantigen-specific/adaptive immune priming

A

By blocking signals or killing lymphocytes:

  1. Calcineurin inhibitors
  2. Proliferation blockers
  3. Monoclonal antibodies

Therefore alloantigen-specific effector functions cannot occur

14
Q

Name the class of drugs used to block alloantigen-specific effector functions

A

Glucocorticoids

15
Q

List the 3 classes of drugs which inhibit the adaptive immune system

A

Block all lymphocyte activity = inhibit ongoing and new adaptive immune system

  1. Anti-proliferative drugs - e.g. methotrexate
  2. Inhibitors of lymphocyte signalling - e.g. ciclosporin
  3. Biologic inhibtors of lymphocyte signalling
16
Q

What are the major differences in therapy between transplantation and autoimmunity?

A
  • Different types of immunosuppressant used in the 2 situations
  • Can provide blanket immunosuppression from 1st day of transplant, unlike autoimmunity
  • Standard best treatment known for transplantation, unlike autoimmunity where a series of drugs are tried to see what works
17
Q

What is the major consequence of immunosuppression (adaptive IS) after transplantation?

A

Increased sensitivity to infection

However adults have already encountered many important pathogens which immune system has created memory cells for and antibodies are long-lived

18
Q

What is AIDS?

A
  • Acquired Immune Deficiency Syndrome
  • Caused by HIV
  • The final stage of HIV infection
  • Body can no longer fight infections
19
Q

How does HIV develop in the body?

A
  • Virus infects CD4 T lymphocytes
  • Increased viral load as decreased CD4 cell count
20
Q

What causes a patient to reach the AIDS stage of HIV infection?

A
  • AIDS results from catastrophic killing of all CD4 T lymphocytes
  • As CD8 killer cells recognise all CD4 cells as virally infected
  • Leaves patient highly sensitive to fungal, viral and bacterial infections
21
Q

What is the first opportunistic infection that many AIDS patients may present with?

A
  • Oral thrush

= infection with Candida fungal infection

  • Also Mycobacterium tuberculosis that may have been latent (dormant)
22
Q

List 3 other opportunistic infections that AIDS patients may present with

A
  1. Shingles (Varicella zoster virus)
  2. Herpes infection (Herpes virus)
  3. Pneumonia (from fungal Pneumocystis carinii)
23
Q

List 2 cancer-causing opportunistic infections which AIDS patients may present with

A
  1. Karposi’s sarcoma (Human herpes virus 8)
  2. B-cell lymphoma (uncontrolled Epstein-Barr virus)
24
Q

In summary, outline the profile of Autoimmunity

A
  • What: Inflammatory damage or specific interference
  • When: Chronic or acute
  • Where: Systemic or organ-specific
  • How: Immune response to self-antigens
  • Why: Often genetic
25
Q

In summary, outline the immune response to Allergy

A
  • What: Inflammation on allergen encounter
  • When: Immunopathology, acute
  • Where: Organ specific (systemic can be fatal)
  • How: Priming to antigens encountered in the environment
  • Why: Possibly genetic
26
Q

In summary, outline the immune response to Transplantation

A
  • What: Killing or inflammatory damage to transplanted organ
  • When: Acute or chronic
  • Where: Transplanted organ
  • How: Immune response to non-self MHC and antigens
  • WHy: MHC diversity