Chapter 21

Question 1

Which cells express MCH class 2?

Answer 1

CD, macrophages and B-cells

Question 2

Which of the 3 pathways of peptide binding are there, which T-cell is activated by which and which pathway is most important for recognition of tumour antigens?

Answer 2

Exogenous - bind to MCH 2 and activate CD 4 + cells, endogenous - bind to MHC 1 (all cells) and activate CD 8+ cells, cross-over pathway display exogenous peptides on MCH 1 and activate CD 8+ cells - this is the most important pathway for recognition of tumour antogens taken up from tumour apoptotic bodies.

Question 3

What is the Mao for imiquimod?

Answer 3

It activates toll like receptors 7 which result in production of interferon-alpha.

INF-alpha induce apoptosis of tumour cells; enhances effect of CTL and NK cells, modulate MHC expression and inhibit tumour angiogenesis

Question 4

How are APCs activated/matured?

Answer 4

By activation of special cell surface receptors or intracellular receptors that recognise PAMPS, these include TLRs, NODs, RIG-1

Question 5

Which lymphocyte has the ability to react to unprocessed antigen, and which will only respond to peptides bound to MHC on APCs?

Answer 5

B cells can respond to unprocessed antigens, and T cells to the APCs

Question 6

Where do you find gamma/delta T cells?

Answer 6

Intestine and skin

Question 7

Memory T cells are ______ positive and can be divided into 2 subtypes ___________ and __________.

Answer 7

CD8+, effector memory and central memory cells.

Question 8

Which IL is essential for T cell proliferation and survival?

Answer 8

IL-2

Question 9

What are tumour-associated antigens?

Answer 9

Antigens expressed preferentially on tumour cells, but often can be expressed on normal cells too

Question 10

Name the 6 different categories of tumor associated antigenes?

Answer 10

Mutated, cancer testis, differentiation, overexpressed, viral , postranscriptionally modified

Question 11

What are the 3 phases of immunosurveillance?

Answer 11

Elimination, equilibrium, escape

Question 12

Name some mechanisms for how tumours can escape the immune system?

Answer 12

Reduce expression TAA, down regulate MCH class 1, negative regulatory immune cell types, immunosuppressive factors produced by tumour cells, surface receptors that reduce T-cell response

Question 13

Which mechanisms may lead to failure of immune-mediated tumour control?

Answer 13

The same mechanisms which regulate autoimmunity; T-cell deletion, T-cell anergy, the function of negative regulatory cells and molecules

Question 14

Name two examples of tumour related immunosuppressive factors?

Answer 14

TGF-beta and IDO

Question 15

Which cells produce TGF-beta?

Answer 15

Tumor associated macrophages and Tregs

Question 16

What is the result of increased TGF-beta production by tumour associated macrophages?

Answer 16

Reduced DC activity by dowregulation MHC and surface DCs. It inhibits IL-12 production (important pro-inflammatory cytokine), interferon-alpha and tumour necrosis factor (TNF-alfa).

Question 17

How does the enzyme IDO excert immunosuppressive effect?

Answer 17

IDO is involved in oxidative catabolism of tryptophan, which is important for. T-cell proliferation and activation. Depletion of tryptophan by IDO activity will therefore result in reduced t-cell activity and response.

Question 18

Name 3 strategies for non-specific immunotherapy?

Answer 18

The use of cytokines, immunological adjuvants and agents that target immunomodulatory molecules.

Question 19

Name 5 examples of nonspecific immunotherapies?

Answer 19

Bacillus of calmette and guerin (BCG)
Interferon alpha
IL-2
Imiqiumod
Anti-CTLA-4 blockade

Question 20

Name 3 examples of specific immunotherapies

Answer 20

Tumour associated peptides, tumour associated proteins, irradiated tumour cells

Question 21

Name 4 examples of adoptive cell therapies

Answer 21

Dendritic cell
Sipuleucel-T
T-cell clones
Tumour infiltrating lymphocytes

Question 22

Alemtuzumab; cancer, molecules, type of mAB

Answer 22

CLL, CD5, Humanized IgG1

Question 23

Bevacizumab; cancer, molecules, type of mAB

Answer 23

Colorectal, lung cancer; VEGF; humanised IgG1

Question 24

Cetuximab; cancer, molecules, type of mAB

Answer 24

Colorectal cancer, EFGR, chimeric IgG1

Question 25

Gemutzumab; cancer, molecules, type of mAB

Answer 25

AML, CD33, Humanized IgG4

Question 26

Ibritumomab tiuxetan: cancer, molecules, type of mAB

Answer 26

non-hodgkin lymphoma, CD20, mouse

Question 27

Ofatumumab; cancer, molecules, type of mAB

Answer 27

CLL, CD20, Human IgG1

Question 28

Panitumumab, cancer, molecules, type of mAB

Answer 28

colorectal cancer, EGFR, human IgG2

Question 29

Rituximab, cancer, molecules, type of mAB

Answer 29

Non-hogkins, CLL, CD20, Chimeric IgG1

Question 30

Tositumomab, cancer, molecules, type of mAB

Answer 30

Non Hodgkin, CD20, mouse

Question 31

Trastuzumab, breast cancer, Her-2/neu, humanised IgG1

Question 32

Define chimeric, humanised and human antibodies

Answer 32

Chimeric- the variable fragment of the antibody molecule is of mouse origin and the constant region is human Humanised- only the hyper variable region is of mice origin, the rest of the AB is human Human- the AB is fully human, usually produced in Chinese hamster ovary (CHO) cells with the desired ab gene.

Question 33

By which mechanisms can antibodies work?

Answer 33

1. Block receptor signalling 2. Trigger receptor signalling 3. Induce cell lysis by activating complement protein cascade or initiation of antibody-dependent cell mediated cytotoxicity 4. Enhance T-cell priming

Question 34

Give an example of a mAB which work both by inhibiting cell signalling and through antibody-dependent cell mediated cytotoxicity?

Answer 34

Trastuzumab

Question 35

How may mAb lead to enhanced T-cell priming?

Answer 35

Lysis of tumour cells result in fragments of the tumour cells, they may bind to TAA-specific antibodies. The complexes can be recognised by FcRs expressed in DCs, and the TAA derived peptides presented to T-cells via cross-presentation

Question 36

Explain antigen-depended cell-mediated cytotoxicity (ADCC)?

Answer 36

The AB bind to a TAA on the tumour cell, the AB is the bound by the FcR, which trigger the cytolytic activity of the NK cell

Question 37

Explain how use of mAB can cause complement activation?

Answer 37

The AB binds to TAA on the tumour cell, a complement protein bind to the Fc domain of the AB/AG complex resulting in a cascade ending in MAC formation which causes pore formation and cell death by lysis.

Question 38

How can

Question 39

How can T-regs suppress the immune system?

Answer 39

1. Directly by killing T-cell and APCs via granzyme B production - reduces the t-cell activity and APC activity 2. Inhibit the ability of effector CTL to kill cells by inhibit release of granzymes 3. Increase IDO production - which inhibit T-cell proliferation 4. Bind IL2- inhibit T-cell proliferation 5. Produce IL-10 and TGF-beta - stimulate differentiation of more Tregs

Question 40

What are the 5 mechanisms tumour cells induce immunosuppression?

Answer 40

1. Avoid immune activation - by increasing inhibitory checkpoint molecules, increase production immunosuppressive cytokines, reduce MHC expression on the cell surface 2. Attract MDSC - by inducing inflammation and release from bone marrow via IL-13 and GM-CSF 3. Activate T-regs 4. Alter DC- effect 5. produce immunosuppresive cytokines