Tumor Immunity Flashcards

1
Q

What are the two main types of tumor antigens?

A

TSA: tumor-specific antigens
TAA: tumor-associated antigens

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2
Q

Which types of tumor antigens are tumor specific antigens?

A

Virus induced: cross reactive and immunotherapy should be applicable to all individuals infected with the cells
Chemical/physical carcinogen-induced : random mutations in affected cell causing AG differences - no cross protection

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3
Q

Which types of tumor antigens are tumor associated antigens?

A

Oncofetal Ag/Carcinoembryonic antigen (CEA): high concentration disappear at birth and return in colorectal cancer
Oncofetal Ag/alpha-fetoprotein: Also expresed in liver during inflammation, high in fetal/maternal, low in adults

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4
Q

What will tumor Ags activate when presented to to the naive cells by APCs?

A

T-cells

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5
Q

When observed histologically, lymphocytes can be viewed around tumors and lymph nodes enlarge. What does this mean?

A

Immune like lymphocyte proliferation responses against tumors inhibit tumor growth

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6
Q

If an immunodeficient individual has cancer what would you observe?

A

An increased incidence of certain types of tumors indicating the immune system protects against tumor growth
“immune surveillance”

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7
Q

What does diminished T-cell function mean to the immune response in tumors?

A

CD4+ T cells can’t secete cytokines that activate macrophages and CD8+ T cells
No CTL mediated tumor eradication

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8
Q

When a transplant is rejected by an animal previously exposed to a specific tumor what occurs?

A

Immunity tumor transplants can be transferred by lymphocytes from a tumor-bearing animal
Tumor rejection is mediated by lymphocytes

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9
Q

How do CD8+ T cells in the adaptive immune system respond to tumors?

A

Perform immune surveillance function recognizing and killing potentially malignant cells that express peptides derived from tumor antigens ad are presented with class I MCH

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10
Q

How do CD4+ T cells in the adaptive immune system respond to tumors?

A

Secrete IL-2 to activate CTLs and IFN-g to activate macrophages

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11
Q

How do antibodies in the adaptive immune system response to tumors?

A

Mediate antibody-dependent cell mediated cytotoxicity (ADCC) so Fc receptors-bearing macrophages or NK cells mediate killing

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12
Q

How does the NK cell respond to tumors in innate immunity?

A

Kills many tumor cell types, espeically with reduced class I MHC expression
ADCC and lysis
IL-12, IL-15 and IFNg inc killing
Lymphokine-activated killer (LAK) cells - IL-2

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13
Q

How does a macrophage respond to tumors in innate immunity?

A

M1: classically activated inhibit tumor growth via TNF inducing thrombosis in tumor vessels

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14
Q

How do tumors escape immune response?

A

Losing expression of Ags
Down regulating MHC-1
Producing immunosuppressive cytokines
Tumor arising in immunologically privileged site

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15
Q

How can tumor gene evade by failure to produce tumor antigen?

A

Antigen-loss variant of tumor cell

Causes the T-cell to be blind to the tumor cell

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16
Q

If a tumor cell lacks an MHC gene what occurs?

A

The T-cell cannot recognize it

17
Q

If a tumor produced an immunosuppressive protein (inhibitory ligand PD-L1) what occurs?

A

T-cell action is inhibited

18
Q

Tumor associated macrophages

A

M2: alternatively activated to promote tumors and spread of cancers by altering tissue micro-environment and suppressing T-cell responses
IL-10, prostoglandin E2, arginase, TGF-B and VEG-F

19
Q

Regulatory T cells

A

Suppress T-cell response to tumors
Number of T-regs inc in tumor-bearing individuals and these cells are found in the cellular infiltrates of certain tumors

20
Q

Myeloid-derived suppressor cells (MDSCs)

A

Suppress anti-tumor innate and T-cell response

21
Q

How can tumors be eradicated by the same effector mechanisms used to eliminate microbes?

A

Opsonization and phagolysis, activation of complement system and ADCC
ex: Anti-CD20 in B cells lymphoma pts

22
Q

What are some ways anti-tumor monoclonal antibodies and destroy tumors?

A

Eradicate tumors the same way as microbes

Use antibodies that can directly activate intrinsic apoptosis pathways in tumor cells

23
Q

Which antibody is specific for oncogene product HER2/Neu?

A

mAB Herceptin

Elicits an immune effector mechanism and interferes with growth signaling functions of HER2/Neu

24
Q

How can there be adoptive transfer of tumor-specific T cells?

A

Lymphoctes isolated from the blood or tumor infiltrate of a pt
Expanded by culture in IL-2
Infused back into pt
Tx often combine w/ systemic IL-2 admin - some tumor regression

25
Q

What are some say to enhance tumor suppression responses?

A

Vaccinating with tumor cells transfected with genes encoding B7 costimulators or cytokine genes
Vaccinate with tumor-antigen presenting dendritic cell
Vaccinate w/ plasmids containing complementary DNAs encoding tumor antigens that are injected directly into pts or use direct transfer of dendritic cells