Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IMMUNOLOGY: CMOD-Block 2 > (20) Tumor Immunology > Flashcards

(20) Tumor Immunology Flashcards

1
Q

Why does the immune system not typically see cancer cells as foreign?

A

They are Derived from Host Tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are carcinomas?

A
  • Cancers of Epithelial Cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are Sarcomas?

A
  • Cancers of Other Cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 3 cancers we see that involve cells of the immune system?
- what characterizes them>

A
  1. Leukemias - involve Circulating Cells
  2. Lymphomas - involves Solid Lymphoid Tumors
  3. Myelomas - involve Bone Marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How can our immune system recognize and kill tumor-specific antigens?

A
  • Abnormal Proteins will be presented on MHC class I molecules
  • Once our CD8’s are primed against that response since these mutant proteins weren’t available during thymic development, they will be able to recognize and kill tumor cells (ideally)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a Tumor Associated Antigen?

A
  • UN-mutated protein that is encoded on the germ-line or somatic DNA of a cell whose EXPRESSION level has been dramatically altered by the neoplastic process
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Do you think that embryonic genes would be recognized as a non-self antigen by the immune system?
- why or why not?

A
  • Recognized as NON-self

Why?:
- Embryonic genes were not being expressed during THYMIC Selection, therefore it is likely that T cells WILL have specificity AGAINST embryonic genes because these T cells would NOT be negatively selected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T or F: overexpression of a normal protein can lead to recognition on death by CTL.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the difference between a tumor Specific antigen and a tumor Associated antigen?

A

Tumor-Specific antigens are MUTATED proteins, they are not a normal part of the host protein make-up nor have they ever been

Tumor ASSOCIATED antigens can be any normal protein that gets overexpressed or expressed at the wrong time (e.g. embryonic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the different outcomes of an experiment were tumor cells are isolated from a mouse and injected into an allogeneic mouse and a syngeneic mouse?
- why is this the case?

A

Syngeneic Mouse:

  • will DIE of Cancer
  • MHC class I from Tumor mouse matches the host MHC class I so proteins nor MHC will be recognized as foreign
  • The cancerous tissue will persist

Allogeneic Mouse:

  • will LIVE and kill the cancer
  • MHC class I from tumor mouse as well as proteins presented by the tumor mouse MHC class I will be recognized as foriegn
  • T cells in our repertoire with specificity for these MHC’s or proteins presented by them will kill the Cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some common proto-oncogenes that can mutate resulting in cancer?
- what do they do?

A
  1. HER2 - Growth Factor Receptor
  2. B-RAF - Intracellular Signaling
  3. MYC - Transcription Factor
  4. RAS - Intracellular Signaling
  5. ß-Catenin - intracellular signaling
  6. VEGF - angiogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some common Tumor Suppressor genes?

A
  1. APC
  2. TP53
  3. RB
  4. CDKN2A
  5. CDK4
  6. p53
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

T or F: mutated forms of tumor suppressor and oncogenes can serve as tumor specific antigens

A

True, they are MUTATED and this USUALLY happens BEFORE thymic selection, therefore the body will not tolerate them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why might T cells be more apt to kill at tumor that has arisen as a result of radiation or chemicals than one that was not?

A
  • Tumors driven by Radiation and Chemicals typically have more mutations and mutations in random (non driver genes)
  • Presentation of these antigens helps the immune system to recognize these cells and kill them
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is MAGE?

  • why is it important?
  • what does it stand for?
  • what other proteins are similar?
A

MAGE
- Melanoma-antigen E

What is it?
- Genes EXPRESSED only in testes but not in other tissues

Importance:
- Testes are immunologically privileged so these proteins were NOT AVAILABLE DURING THYMIC SELECTION

  • This means is be a TARGET FOR CTLs

Others:
GAGE, BAGE, RAGE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the advantage to making a vaccine to MAGE, BAGE, CAGE, or RAGE?

A
  • If you body is primed to respond against these it will mount a quicker, more effective response with a mutation in a cancer cell causes expression of MAGE, BAGE, CAGE, or RAGE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is an effective treatment for NER2/NEU mutations?

- why is this the case?

A
  • Overexpressed protein in many Breast Cancers

- We can thus block it used mAb therapies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are oncofetal antigens?

- how does the immune system respond to these?

A
  • Genes that are normally expressed only during embryonic development but are DE-repressed in Tumors
  • Immune system can mount a potent response against these
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does the glycocalyx of a cell change once it has become a tumor?
- what is the clinical significance of this?

A

Glycocalyx - will have elevated levels of glycoprotein and glycolipid or mutated forms of these macromolecules

  • This is clinically significant because we can use this for DIAGNOSIS and for treatment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are CA-125 and CA-19-9?

- what are they indicative?

A

Mucins - glycoprotein component of mucus

  • Ovarian Carcinomas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is MUC-1?

  • what is it indicative of?
  • response mounted?
A

Mucin

MUC-1 contains TUMOR SPECIFIC carbohydrate and peptide epitopes (INDUCES BOTH B and T CELL RESPONSE)

  • Breast Carcinomas
22
Q

What are Cell-Type Specific Differentiation Antigens?

- why are they important?

A

Antigens expressed at different Developmental Stages of different cell types.

Important because Cancer Cells often RETAIN these markers and this tells us where the cancer is coming from

23
Q

What cell-type specific differentiation antigen would you be looking for in a B cell lymphoma?
- what drug targets this marker?

A
  • CD20

- Rituximab (mAb) targets CD20

24
Q

T or F: the body makes anti-bodies that are specific to Cell-Type Specific Antigens.

A

False, we don’t do this because these are normally expressed on our cells

25
Q

What cell marker would you look for in a cancer caused by thymocytes?
- what is this cancer called?

A

CD1

  • T lymphoblastic Leukemia (T-all)
26
Q

If you see CD3 and either CD4 or CD8 on the surface of a cancer cell, how do you know where it came from and when?

A

T cell Derived

Cancer Came about AFTER reaching the Thymic Medulla

27
Q

Why can the immune system more adequately react to cancers caused by viruses?

A

These cancers should express VIRAL antigens that will be recognized as foreign by T cells

28
Q

What are some common DNA viruses that cause cancer?

- what kind of cancer?

A

Papillomavirus -Carcinoma of Uterine Cervix
HBV - Hepatocellular Carcinoma
EBV - Burkitt’s Lymphoma, Nasopharyngeal Carcinoma

29
Q

What are some common RNA viruses that cause cancer?

- what kind of cancer?

A

Human T-cell Leukemia Virus Type 1 (HTLV-1) - Adult T cell leukemia

HIV-1 - Kaposi’s Sarcoma

30
Q

What virus causes B-cell lymphoproliferative disease?

A

Epstein-Barr Virus

31
Q

What treatment can be used to prevent Virally derived cancers?
- why?

A

We can make vaccines for these like GARDASIL because there are foreign antigens present

32
Q

What mechanism do 1/3 to 1/2 of tumors use to evade the acquired immune system?

A

1/2 to 1/3 of tumors down regulate MHC class I expression to evade CTL killing

33
Q

Besides down regulating MHC class I on their surfaces, what are 3 other methods that cancer cells use to avoid immune surveillance?

A
  1. Secrete immunosuppressive cytokines like TGF-ß to create an immunosuppressive environment around the tumor
  2. Some express Fas ligand and cause immune cells to undergo apoptotic Death
  3. Some tumors express PD-L1
34
Q

What is PD-L1?

A

PD-L1 is a ligand for PD-1 that is expressed on the surface of T effector cells to down regulate their effector function

35
Q

In what ways can we use humanized monoclonal antibodies to treat cancer?

A
  • hmAbs can work as ligand agonists or antagonists
  • hmAbs can be conjugated to toxins or Radionucleotides for killing tumor cells
  • hmAbs can also be used to target cells for killing by NK cells (ADCC) and via the complement cascade
36
Q

In what 6 ways can mAbs act on cancer cells?

A
  1. Direct Delivery
  2. Receptor Blockage
  3. Ligand Blockage
  4. Receptor Downregulation
  5. Signal Induction
  6. Depletion
37
Q

What is depletion in terms of mAb cancer drugs?

- examples?

A

Depletion:
- You attract T cells or NK cells to the cancer cell so that it can be killed.

Example:
1. Rutiximab binds to CD20 and attracts NK cells to do ADCC

  1. Sometimes mAbs can attract so much MAC that the cells anti-complement regulators are overcome and the cell dies by lyses
38
Q

What are Trastuzumab, Pertuzumab, and T-DM1 all used to treat?

A

Breast cancer

39
Q

Which of the anti-cancer drugs binds to HER2?

- how does is work?

A

T-DM1

  • Binds to HER-2 preventing it from binding with HER-3
  • It also carries a chemotherapy drug with it, making it good for pre-treated HER2-positive breast cancer
40
Q

What drug(s) bind(s) the Epidermal Growth factor Receptor to prevent breast cancer growth?

A
  • Cetuximab

- Panitumumab

41
Q

What is Lymphokine activated Killer Cell Therapy?

- how does it work?

A
  • PMBC (peripheral mononuclear blood cells) are obtained from the patient and treated with IL-2 ex vivo
  • IL-2 activates NK cells so that they can now perform their effector function more effeciently
  • NK cell can become better at recognizing ADCC, MIC, and lack of MHC class I
42
Q

What is the point of making mAb drugs that have specificity for CTLA-4?

A

CTLA-4 is found most frequently on Tregs

CTLA-4 has high affinity for B7 and its binding

Treg Binding has 2 main affects

1) CD28 cannot bind to C7 if its all bound by CTLA-4
2) When Tregs release TGF-ß when they bind preventing T cell proliferation

43
Q

What mechanism do melanomas often use to evade host cell defenses?

A

PD-L1 expression

44
Q

What does PD-L1 do?

- why does it confer a selective advantage for forming tumors like melanomas?

A

PD-1
- Member of CD28/CTLA-4 family and is expressed on EFFECTOR T cells

  • Binds to its ligands PD-L1 or PD-L2 that are NORMALLY expressed in by APCs in secondary Lymph Tissue
  • DOWN REGULATES CTL’s to keep them from performing their Host function until they’ve left the 2˚ Lymphoid Tissues
45
Q

What happens when PD-L1 or PD-L2 get expressed on Cancer cells?
- what is the advantage of making a mAb drug that is PD-L1 or PD-1 specific?

A

PD-L1 on a cancer cell keeps the CTL from killing it

Advantage of mAb is it binds either PD-L1 or PD-L2 and prevents the two from interacting and CTLs can still perform their effector functions on cancer cells

46
Q

How do Bispecific mAbs work?

A

Antibodies that have specificity for CD3 on one heavy chain and light chain pair and specificity for a target on the cancer cell as the other

  • THIS RESULT IN CTLs KILLING THE CANCER CELL AS IF IT HAD RECOGNIZED AN MHC WITH NON-SELF DETERMINANTS
47
Q

How does Blinatumomab work?

A
  • Bispecific mAb drug with anti-CD3 specificity on one side and anti-CD19 specificity on the other
  • used to fight B cell Lymphomas that are expressing CD19
48
Q

What is a CAR?

- what is the advantage to CAR?

A

Chimeric Antigen Receptor

Patient Specific Therapy where Antibodies are put onto CD8 T-cells where they can work like a TCR to recognize bad cells

How it works:

  • Make in vitro Ab response to the patients tumor antigens
  • Rearranged genes are inserted into a gene that connects them to a CD3 zeta-chain
  • T cells expressing this gene are cultured and re-inserted into the patient and can now be activated in 2˚ lymphoid tissue to kill the tumor
49
Q

When is it most beneficial to use IL-2 therapy?

- what cell type is targeted by this therapy?

A
  • NK cells are targeted
  • This is beneficial when MHC class I is no longer expressed on the tumor cells (NK cells should recognize this deficiency and Kill the cancer cells)
50
Q

What is a potential link between the adaptations that our cancer cells make and pregnancy?

A

Growth:
- Embryo is a rapidly growing mass of cells that has non-self antigens on the its cell surfaces

Placenta: 
- Placenta down regulates MHC class I expression and secretes TGF-ß to prevents the mom from mounting any kind of immune response
51
Q

How does therapy with PD-1/PD-1L and CTLA-4 binding antibodies work?

A

CTLA-4:

  • Present on Tregs and binds B7 with higher affinity than CD28
  • Tregs recognize self-antigens and secrete TGF-ß to down regulate T cells near it that may also be binding to self-antigens
  • DE-REPRESSING and lifting peripheral tolerance mechanism allow for MORE T cell EFFECTOR ACTIVITY (not necessarily more activation)

PD-1/PD-1L:

  • Acts in 2˚ lymph. to prevent CTLs from acting on APCs but some cancers also expresses it to down regulated CTL effector mechanisms
  • Cancers may also express this to inhibit CTLs
52
Q

What is your main risk using CTLA-4 and PD-1/PD-1L therapy?

A

CTLA-4:
- Lifting peripheral tolerance could trigger autoimmune type effects

PD-1/PD-1L:
- Lifting this could allow some CTLs to attack inside 2˚ lymph tissue

IMMUNOLOGY: CMOD-Block 2 (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions