Immunity to Cancer Flashcards

1
Q

-RECAP-

What do MHC molecules do?

A

Major histocompatibility complex.
They display internally processed antigens inside a cell.
MHC 1: self-protein
MHC 2: only on cells of the immunity

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2
Q

-RECAP-

What processes are involved in the innate, and adaptive immunity?

A

Innate: Phagocytosis, opsonisation, complement system

Adaptive: T/B cell proliferation, antibody production

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3
Q

Which type of T cells bind to MHC class I, and which binds to MHC class II?

A

MHC class I: cytotoxic T cells

MHC class II: T helper cells

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4
Q

What are RAG1 and RAG2 genes?

A

They are recombinant activating genes which repair double stranded DNA breaks in lymphocytes (T/B).

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5
Q

What happens if RAG1/RAG2 genes are knocked out?

A

We can breed animals so they don’t repair these lymphocyte damages, and so T/B/NK cells are eradicated.
This hence induces carcinogenic induced tumours in these animals.

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6
Q

What are RAG knockout mice more prone to?

A

Spontaneous tumours.

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7
Q

What is associated with melanoma, bladder, colon, lung, pancreatic, and kidney tumours?

A

Immunosuppression (due to the drugs taken post-surgery), which increases cancer risk.

These are non-viral cancers.

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8
Q

Experimentally, what is the immune response of carcinogen induced tumours, spontaneous animal tumours, and viral/UV associated tumours?

Which one of these tumours is also a very good candidate for vaccines?

A

Carcinogen induced tumours: weakly immunogenic, does not produce a strong immune response

Spontaneous animal tumours: weakly immunogenic, as above

Viral/UV: strongly immunogenic, very good candidates for vaccines e.g. HPV for cervical/oral cancers

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9
Q

What surrounds a tumour?

A

Mononuclear cell infiltrates (immune system cells), e.g. activated T/NK cells, and macrophages

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10
Q

What are the 2 classifications of tumours, based on their patterns of expression?

A
  1. Tumour specific antigen (TSA): tumour itself produces the antigens
  2. Tumour associated antigen (TAA): tumour creates a system where whatever its making is associated with the antigens
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11
Q

What can T cell recognition of these tumour cells be induced from?

A
  1. Over-expression of self-protein
  2. Expression of oncogenic virus antigens, e.g. HPV
  3. Expression of antigen from an oncogene/mutated suppressor gene
  4. A mutated self protein
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12
Q

Which T lymphocyte recognises tumour antigens?

A

Cytotoxic T cells.

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13
Q

What can poor natural killer cell function lead to in cancer?

A

Poor NK cell function = future metastasis (fragments of the cancer migrating to other parts of the body)

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14
Q

What can the absence of NK cells lead to?

A

An increase of spontaneous tumours.

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15
Q

What is the process in which NK cells kills tumour cells?

A
  1. NK cell releases granzymes, which produce caspases
  2. This induces apoptosis of the NK cell
  3. Fas ligand generated which binds to the receptors on the tumour cell and causes nuclear destruction (apoptosis)
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16
Q

What do NK cells bind to?

A

Antibodies surrounding a tumour

17
Q

What do NK cells depend on when killing a tumour cell?

A

The presence of antibodies, as NK cells don’t have T cell receptor binding.

18
Q

What is the linkage between the innate and the adaptive immune system in cancer?

A
  1. Tumour antigen expressing cells are phagocytosed by dendritic cells
  2. Dendritic cells digest them, so antigens are present on its MHC I & MHC II surface
  3. Dendritic cell travels up to the lymph nodes, where it comes to contact with a T cell
  4. The APC presents its antigens to T cells and causes their activation
  5. Activated T cells proliferate and kill the cells expressing the tumour antigen
19
Q

How does the adaptive system respond to a tumour cell?

A

Cytotoxic T cells kill the tumour via granzymes, perforin & Fas ligand.

T helper cells release pro-inflammatory cytokines e.g. IGN-gamma, IL-2 and IL-4.

Dendritic cells also release TNFa, and H2O2 to aid in cell death.

20
Q

Why is it hard to detect the early stages of cancer?

A

Because cytotoxic T cells control the tumours in the early stages, so by the time we detect it, these T cells would be resistant to the immune system.

21
Q

What do T helper cells in cancer produce?

A

IFN-gamma & promotion of T regulatory + B cells.

22
Q

What happens if IFN-gamma is neutralised in cancer?

A

The protection of CD4 T helper cells gets abolished.

23
Q

Which type of antibody is highly increased in cancer?

A

High levels of IgG are present around the tumours.

24
Q

What can be a valuable treatment in cancer?

A

Monoclonal antibodies.

25
Q

What is the humoral response to tumour cells?

A

Antibodies would activate complement, causing opsonisation, phagocytosis and MAC.
Opsonic fragments from the complement system would cover the tumour cell, readying it for phagocytosis, MAC, and inflammation to attract other cells.

26
Q

What are some factors that can interfere with the recognition of tumour cells by T cells?

A
  1. Tumours sometimes do not produce antigens, so T cells don’t recognise them
  2. Mutations in MHC genes, causing T cell non-recognition
  3. Tumours can produce immunosuppressive proteins that can inhibit T cells.
  4. No induction of anti-tumour T cells
27
Q

What can tumour cells produce that binds to WBC’s and causes them to apoptose?

A

They can secrete soluble Fas ligand, which causes this.

28
Q

What are the aims of immunotherapy?

A
  1. Produce a vaccine with tumour antigens
  2. Enhance the immune system to tumours
  3. Passively be T cells/antibodies
29
Q

What are some benefits of cancer vaccines?

A
  1. Uses the own body’s immune defence mechanisms
  2. Less side effects
  3. Prevents against virus-associated cancers
  4. Provides an alternative to chemotherapy (which just kills everything)
30
Q

What are some potential side effects of cancer vaccines?

A
  1. Cold/flu-like symptoms
  2. Redness/itching/soreness at injection site
  3. Muscle/joint aches and pains
  4. Potential autoimmune disorders
31
Q

What are the 2 potential mechanisms of action of a cancer vaccine?

A
  1. Dendritic cells are pulsed through - antigens are presented to them
  2. Dendritic cells are transfected - gene for the tumour is put into a bacterial plasmid & is expressed inside the dendritic cell