Thrush- Tumor Immunology

Question 1

cancer cells are ____ self cells. they may express diff markers and have abnormal growth control. (lack of apoptosis, and p53 mutations)

Answer 1

altered

Question 2

what is a malignant cancer cell? what is metastasis

Answer 2

when cancer cells invade other cells and go where they are not supposed to be

Question 3

what are the different mutations

Answer 3

1. chemical carcinogens; nitrates, asbestos, nicotine/tar
2. physical carcinogens; UV light (sun), radiation
3. viruses; Human T cell lymphotrophic virus 1 (HTLV-1), Epstein Barr virus (EBV), hepatitis virus, human papillomavirus (HPV)

Question 4

Because of the mutations, cancers are:

Answer 4

1. complex genetic disease
2. heterogenous; constant changes and evasion of host control
3. often has lack of antigenicity; derived from host
4. metastatic; able to move form one location to another

Question 5

how do you increase gene expression

Answer 5

move regulatory gene next to a diff promoter region.

Question 6

____ gets expressed in certain situations and not. if moves to a gene that is always turned on, the gene constantly gets turned on, B cell proliferates and you get burst lymphoma (8–> 14). If you move cyme next to T cell receptor enhancer, it won’t be a problem. (usually silenced)

Answer 6

c-myc

Question 7

colon cancer is due to_____mutations in a stepwise fashion. You make a mutation in a tumor suppressor gene, then the protein that was encoded by the gene is not working well then you get mutation in oncogene and other TSG’s until you get to the stage of metastatic cancer.

Answer 7

multiple

Question 8

There is a variable immune response, Since ____ derived (self), tumors may not be recognized as foreign = no immune response. Also if immunosuppressed, increased incidence of cancer formation. Some tumors do have significant antigenic determinants and can be recognized as “altered.” –>melanomas (uv light), or virally induced tumors. Tumor infiltrating lymphocytes are usually suppressed

Answer 8

host

Question 9

what are tumor antigens

Answer 9

Ag expressed only by the tumor, therefore they are abnormal/foreign antigens. Reality is there aren’t a lot of these out there.

Question 10

what are tumor associated antigens

Answer 10

not unique to tumor cells but there is something abnormal about them. Normal proteins, but not normal proteins for an adult. (expressing moleucules at abnormal time in stage of development). may be proteins expressed at low levels in normal cells but much higher on the cancer cell.

Question 11

what are the two categories of tumor antigens

Answer 11

1. tumor specific

2. tumor associated antigens

Question 12

what are oncofetal antigens

Answer 12

normal proteins exp during fetal dev but during cancer formation they get formed again. CEA is found in some colon cancers and these levels of marker proteins could be used to measure cancer burden

Question 13

what are markers of oncofetal antigens

Answer 13

1. Carcinoembryonic antigen (CEA): found in some colon cancers and also can be used to measure cancer burden.
2. Alpha fetoprotein (AFP): increased in hepatitis or pregnancy. It can also mean they have cancer; found in patients with liver and germ cell tumors.

Question 14

___ antigens; you can have viral proteins by expressed and presented with MHC class I.

Answer 14

viral;

Question 15

what are the oncoviral proteins associated with?

Answer 15

HPV type 16, E6, and E7 proteins
Nautre of antigen: viral transforming gene products.
Tumor type: cervical carcinoma

Question 16

surface immunoglobulins are associated with ____

Answer 16

lymphoma; specific IG after gene rearrangements in B cell clone.

Question 17

if tumor antigens, why no immune recognition

Answer 17

tumor related immune evasion

1. lack of antigenic epitope; self cells (not exp # of foreign antigens)
2. decreased MHC expression; Class I (unless b cell lymphoma); deficient antigen processing
3. lack of costimulation: cells reduce levels of B7 (imp in activating T cells)
4. produce inhibitory substances: such as cytokines
5. shedding of tumor antigens: tolerance induction due to a certain protein

Question 18

How to you detect tumors

Answer 18

1. radioimmunoassay, immunoelectrophoreis, ELISA of secretion/sera/urine for:
2. myeloma proteins: look for B cell tumors
3. oncofetal antigens: CEA or AFP
4. alkaline phosphatase: prostate and liver cancer
5. prostate specfic antigen (PSA): normal protein expressed at higher levels in prostate cancers

Question 19

You see increased level of CEA in some types of cancer or pathology. These antigens are tumor associated but just bc you see increased level it could also be _______ not just cancer.

Answer 19

pathological

Question 20

_____ moniters certain tumor markers on cells in the blood (flow cytometry) or in situ (microscopy)

Answer 20

immunoflourescnce

Question 21

How do you detect minimal disease to see if the tumor will come back in the future

Answer 21

1. PCR: detects cancer genes witihin cell

2. changes in cytokine level:

Question 22

what are conventional therapy of cancer

Answer 22

1. surgery
2. radiotherapy
3. chemotherapy

Question 23

what is passive immunotherapy

Answer 23

1. monoclonal Ab to tumor specific antigens–> to cause ADCC and/or C’ activation
2. monoclonal Ab to signal apoptosis–> Ab binding to Fas protein
3. monoclonal Ab to prevent angiogenesis: tumors need to stimulate blood vessel formation if they are to grow beyond 1mm

Question 24

_____ is a major marker on B cell

Answer 24

CD20

Question 25

If you have Ab against Ag, Ab had to be gen in animal that rec protein as foreign. If you take mouse Ab and put it ind it will bind to cancer cells and kill them, but you can't use mouse An amymore cause it will recognize antigen as foreign, You can _____ these Ab --> molecular attach human Fc region. Amount of mouse foreign molecule is reduced.

Answer 25

humanize

Question 26

_____ is where you stick something to other proteins. Where you deliver toxicity specific to cancer cells.

Answer 26

conjugate

Question 27

what is active immunotherapy

Answer 27

1. tumor infiltrating lymphocytes: Isolate T cells,a ctivate with IL-2 and put them back in. 2. Dendritic cells pulsed with tumor antigens: allows for better antigen processing/presentation and costimulation. 3. Bone marrow transplant: can be useful for some tumors of lymphoid origin. 4. cytokines: to activate an immune response ("break" suppression). 5. Vaccination: Good for viral infection; papilloma virus vaccine for cervical cancer

Question 28

What are select FDA approved cytokines for cancer therapy

Answer 28

1. IL-2: helps CD8 T cells and NK cells (altered self cells); get cells activated to prevent suppression and respond to cancer. (inc. vascular permeability) 2. IFN-alpha: stimules better immune recognition by enhancing MHC expression along with Ag on the surface of the tumor cell.

Question 29

_____ is an antiviral cytokine

Answer 29

IFN-alpha

Question 30

future includes new tumor _____ as well as ____ antibodies

Answer 30

vaccines; bispecific