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Immunology Pt. 2 > Transplantation and Tumor Immunology > Flashcards

Transplantation and Tumor Immunology Flashcards

1
Q

Define autograft.

A

Self-donation

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2
Q

Define syngraft.

A

Genetically identical recipient

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3
Q

Define allograft.

A

Genetically different recipient

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4
Q

Define xenograft

A

Graft to/from a different species

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5
Q

What are the two ways a recipient’s T cells recognize a graft?

A
  1. T cells regognized processed donor peptides that are presented by recipient APCs.
  2. Recipient T cells recognize unprocessed donor MHC molecules on graft APCs.
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6
Q

What are the three types of rejection?

A
  1. Hyperacute
  2. Acute
  3. Chronic
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7
Q

How long does it take for hyperacute rejection to occur?

A

Minutes or hours

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8
Q

How long does it take for acute rejection to occur?

A

10-14 days

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9
Q

How long does it take for chronic rejection to occur?

A

Months or years

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10
Q

What is hyperacute rejection mainly due to (what is the mechanism)?

A

Due to pre-formed antibodies in the recipient, activating complement system - Abs could have been formed due to a previous blood transfusion.

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11
Q

What are the four mechanisms involved in acute rejection?

A
  1. Direct contact between CD8+ cells and the graft - release of perforin and granzyme, Fas L expression.
  2. Locally released cytokines and chemokines –> inflammation, macrophage activation, infiltration of phagocytic cells.
  3. Antibody attack against donor HLA molecules –> complement binding and ADCC by NK cells.
  4. Direct NK cell attack
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12
Q

What cells/factors are responsible for chronic rejection?

A

Ab, T cells and NK cells attack the graft.

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13
Q

What major disease sometimes arises after stem cell transplantation?

A

Graft vs. host disease (GVHD).

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14
Q

How does graft vs. host disease (GVHD) work?

A

Some CD4+ T cells that were present in the graft recognize the host antigens and proliferate and cause a “cytokine storm” that recruits cell-mediated effectors and results in inflammation.

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15
Q

What are three requirements for graft vs. host disease (GVHD) to occur?

A
  1. Graft must contain live T cells
  2. Recipient must be immunosuppressed
  3. Donor and recipient must have different HLA types (no identical twins)
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16
Q

Name two drugs that block calcineurin.

A

Cyclosporine and FK506

17
Q

What does calcineurin do?

A

A phosphatase that is activated during T-cell binding of MHC+peptide that stabilizes IL-2 and IL-2R mRNA —> T cell activation

18
Q

Do corticosteroids block cytokine production?

A

For sho

19
Q

What do anti-CD3 and anti-IL2R monoclonal antibodies do?

A

Block T cell activation!

20
Q

What might virally-induced cancer cells express on their surfaces?

A

Virally-controlled antigens, modified glycoproteins, etc.

21
Q

What are oncofetal antigens and how do they relate to cancer?

A

They are normally only expressed during fetal development that can be expressed in adulthood in malignant cells.

22
Q

Name two oncofetal antigens.

A
  1. Alpha-fetoprotein (primary hepatocellular carcinoma)

2. Carcino-embryonic antigen (colon/GI cancers and breast cancers)

23
Q

Name an anti-Her2/neu drug

A

Herceptin (MAb with immunotoxin attached)

24
Q

Name tissue-specific differentiation antigens that are often increased in prostate cancer and separately in lymphomas.

A

Prostate-specific antigen (PSA) in prostate cancer.

B and T cell markers are examples (CD19, 20, CD3, 4, 8 etc.) in lymphomas.

25
Q

Do tumors sometimes lose their HLA class I molecules?

A

Yup

26
Q

Which immune cells kill cells that have lost HLA class I molecules?

A

NK cells through the direct mechanism with perforin and granzyme, FasL

27
Q

Are NK cells large granular lymphocytes?

A

Yeah

28
Q

What type of NK cell receptor is involved in ADCC?

A

Fc-gamma binds IgG on cells that need to die

29
Q

Which cytokines can activate NK cells? (name 3)

A

IL-2, IL-12, IFN gamma

30
Q

What is the principal mechanism of cell-mediated tumor rejection?

A

Killing by CD8+ cells with granzyme, perforin and FasL

31
Q

Can NK cells and macrophages kill tumor cells?

A

Yeah

32
Q

Name three ways in which tumors evade the immune system.

A
  1. They release immunosuppressive factors like IL-10 and TGF-beta.
  2. They release factors that activate Tregs (which also release IL-10 and TGF-beta).
  3. They select antigen-negative variants (they express antigens that don’t evoke immune response).
33
Q

Name two drugs that stimulate innate immune system responses to fight cancer.

A

Imiquimod activates TLR-7, BCG produces bladder inflammation to fight bladder cancer.

34
Q

Name two immunotoxic monoclonal antibodies that are used to fight lymphoma, and some breast cancers, respectively.

A

Rituximab targets CD20 on B cells to fight lymphomas, Herceptin targets Her2/neu in some breast cancers.

Immunology Pt. 2 (10 decks)

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