Studied by 8 people
Which of the following is true of about half of the CT antigens?
a. They are expressed by somatic cells.
b. They are not immunogenic.
c. They are encoded on the X chromosome.
d. They are expressed only by males.
c
Which of the following circumstances put an individual at a higher risk of developing cancer than most individuals in the general population?
a. immunodeficiencies affecting key components of the immune system
b. overexpression of tumor suppressor proteins
c. heterozygosity in HLA class I region genes
d. immunosuppressive drugs taken by individuals with transplants who have chronic autoimmune diseases
a, d
Which component of the melanoma cell that represents a tumor-specific antigen?
a. gp100
b. proteasome
c. sliced peptide (40, 42, 47, 52)
d. sliced peptide (43, 46)
c
The figure shown is a light micrograph of a tumor section that has been stained to identify the expression of HLA class I. Brown staining is indicative of the presence of HLA class I molecules. As noted by the relatively limited amount of brown staining, this micrograph shows how tumors can lose the expression of HLA class I.
What are the implications of this result for the immune response against the tumor?
a. Tumor cells are resistant to T-cell attack.
b. Tumor cells are susceptible to anti-tumor antibody.
c. Tumor cells are susceptible to NK-cell attack.
d. Tumor cells have enhanced Treg activation ability.
a, c
The majority of individuals with cancer make adaptive immune responses against which of the following?
a. oncogenic viruses
b. tumor antigens
c. mutagens
d. normal self antigens
b
Human epithelial tumors expressing MIC glycoproteins are attacked by which of the following cell types?
a. CD8 T cells
b. γδ T cells
c. NK cells
d. Treg cells
e. M cells
a, b, c
In the majority of cases of chronic myelogenous leukemia (CML), a novel fusion protein (BCR–ABL) is the cause of malignant transformation. Which of the following are true of peptide antigens that span the point of fusion?
a. They can be presented by HLA class I and class II molecules.
b. They are an example of cancer neoantigens.
c. They are produced by peptide splicing.
d. They are cryptic epitopes that are hidden from the immune system.
a, b
Which of the following is true regarding tumor-specific antigens?
a. They are not associated with viral proteins because tumor-specific antigens are encoded only in the human genome.
b. They are unique to tumor cells and not expressed in normal cells.
c. They are associated only with hybrid proteins that arise through gene recombination.
d. They are found in both normal and tumor cells, but in normal cells their levels are significantly reduced.
b
How do MIC glycoproteins have the capacity to negatively regulate tumor immunity?
a. They transmit either activating or inhibitory signals to NK cells when bound to tumor cells.
b. They exert different effects in the membrane-bound versus the soluble form.
c. They stabilize or destabilize HLA class I molecules on the surface of cancer cells.
d. They deliver either an apoptotic or a mitogenic signal to the cancer cell upon ligation.
b
The figure shown documents the growth of a breast cancer in an individual. This figure also illustrates which of the following?
a. the formation of cancer neoantigens
b. the benefit of adjuvant effect in cancer treatment
c. a failure of immunosurveillance
d. the accumulation of mutations
c
What is the term for the process in which the immune system continuously searches the body for cancer development?
a. anti-angiogenesis
b. transformation
c. metastasis
d. immunosurveillance
d
Which of the following have potential as therapeutic interventions for cancer immunotherapy to treat epithelial tumors?
a. an antibody or small molecule that shields membrane-associated MIC from proteolysis
b. neutralizing antibody specific for soluble MIC
c. high-affinity soluble MIC proteins engineered to outcompete endogenously secreted MIC proteins
d. anti-NKG2D antibodies that cross-link and stimulate NK cells
e. anti-MIC antibodies that stimulate antibody-dependent cytotoxicity of NK cells
a, b, e
How does bladder instillation of viable Mycobacterium bovis (BCG vaccine), a treatment for superficial bladder cancer, mediate its antitumor effect?
a. by stimulating TLR9
b. by inducing a state of T-cell exhaustion
c. by activating IL-17-secreting γδ T cells
d. by stimulating cross-reactive antibodies that recognize tumor antigens on the surface of tumor cells
e. by inducing a state of chronic inflammation
a, c, e
What is a major difference in how the immune system responds to cancer cells versus virus-infected cells?
a. cancer does not induce inflammation
b. only innate immune responses are activated in response to cancer
c. the tempo of the immune response
d. NK cells respond to virus-infected cells but are unable to recognize cancer cells
c
Which of the following is not an example of how cancer cells evade or manipulate the immune response?
a. TNF-α expression
b. TGF-β expression
c. downregulation of HLA class I molecules
d. induction of anergy
e. endocytosis of NKG2D
a
What can HPV vaccines do?
a. prevent cancer caused by existing infections
b. prevent infections by HPV
c. stimulate immune responses that eliminate established virus infections
d. stimulate an antitumor response against an established cancer
b
Which of the following correctly describe a tumor-associated antigen?
a. an antigen whose peptides are presented at higher levels by a tumor cell compared with a normal cell
b. an antigen that is not expressed in any normal cell
c. an antigen encoded by an embryonic gene that is expressed abnormally in a differentiated cell
d. an antigen that derives from a viral protein
a, c
How is the soluble form of MIC glycoprotein made by epithelial tumor cells?
a. Soluble MIC is a component of the cell debris from dying cancer cells.
b. Differential mRNA splicing gives rise to an alternative isomer of the MIC protein that lacks a transmembrane region.
c. The tumor cells express a protease that releases the MIC protein from the cell surface.
d. Cell-surface MIC is cleaved from the surface of tumor cells undergoing apoptosis by apoptosis-induced proteases.
c
When is the immune system best equipped to eliminate cancer?
a. after the cancer cells acquire more genetic variance
b. before cancer cells acquire neoantigens
c. when cancer-cell numbers are small
d. after cancer cells colonize multiple sites
c
HPV vaccines contain which recombinant protein?
a. L2
b. E1
c. E6
d. L1
d
What is the name for the small proportion of tumor cells that are self-renewing and exhibit higher levels of resistance to chemotherapeutic agents and radiation compared with most of the other cells in the same tumor?
a. cancer stem cells
b. centroblasts
c. carcinogens
d. carcinomas
a
What HPV protein activates telomerase?
HPV E6
Which of the following are associated with cervical cancer?
a. The HPV DNA integrates into the genome of infected cells.
b. L1 and L2 inhibit tumor suppressor proteins.
c. The cancer cells express elevated levels of tumor suppressor proteins.
d. It is caused by oncogenic human papillomavirus (HPV).
e. Telomerase is activated in cancer cells.
a, d, e
What type of DNA damage is induced by chemical carcinogens?
produce single-nucleotide substitutions in DNA
What type of DNA damage is induced by radiation?
DNA strand breaks, nucleotide cross-links, abnormal recombination, and chromosomal translocation
What tumour is associated with papillomavirus?
Genital warts (benign), Carcinoma of uterine cervix
What three types of cancers are induced by the epstein-barr virus?
Burkitt’s lymphoma (cancer of B lymphocytes)
Nasopharyngeal carcinoma
B-cell lymphoproliferative disease
What 2 viruses cause kaposi sarcoma?
Human herpesvirus 8 and HIV-1
What reasons do the immune system not readily detecting cancers?
Cancers are not infectious agents so they do not have PAMPs
Tolerance
What results in tolerance of tumour antigens?
Lack of T cell co-stimulation
How do tumours induce tolerance?(active tolerance)
secreting factors such as IL-10 and VEGF to make nearby dendritic cells tolerant. Tumours also secrete other factors like TGF-beta to suppress T cell activation, proliferation and differentiation.
How do tumours evade the immune system?
tumour cells are derived from normal cells, so they don’t have NONSELF determinants
adaptive immune cells do not usually enter tissues unless they have been recruited there by innate cells as a result of PAMP-initiated inflammatory response. As cancer cells lack PAMPs, the innate cells cannot bind them, and consequently cannot recruit the adaptive immune cells to the tissues.
Lack of PAMPs
Dendritic cells in the tissues are immature and do not migrate to lymph nodes to present antigen unless activated by a PAMP or another source of pattern recognition receptor stimulation-such as DAMP (danger associated molecular pattern-a structure or molecule produced by necrotic cells and which provides danger signals to activate the immune response following tissue damage).
Therefore a tumour neoantigen will be ignored by the immune system unless presented by a mature dendritic cell so tolerization to the tumour antigen will occur-this occurs passively.
Why do tumours recruit tumour-associated macrophages and neutrophils?
Proliferation and progress
Why do tumours secrete pro-inflammatory cytokines and chemokines (such as IL-1, il, IL-8)?
Drive tumour growth
Purpose of tumours secrete pro-inflammatory
cytokines and chemokines (such as IL-1, IL-6, IL-8)?
recruit neutrophils and macrophages which produce cytokines that promote proliferation of the tumour and angiogenesis (growth of new blood vessels) that are required for rapidly growing cells
What induces DNA mutations that drive disease
progression and metastasis?
tumour associated inflammatory cells, especially macrophages produce reactive oxygen and nitrogen species
What correlates with poor prognosis in 80% of cancers?
macrophage density
How can macrophages support tumour growth?
Tumours produce anti-inflammatory cytokines (IL-10 and TGFβ)
How can tumours maintaining an inflammatory response be treated?
neutralizing antibodies against the cytokines driving tumour growth and angiogenesis, or by giving the patients anti-inflammatory drugs
What leads to the recruitment of macrophages, neutrophils, myeloid-derived suppressor cells?
Pre-exisiting inflammatory condition
Infection
Oncogenic mutations
Senescent cells
Cell associated DAMP release
These all produce inflammatory mediators
Li Frameni Syndrome
p53 mutation (increases risk of cancer as they only have one functional p53 allele)
Mutagens
Increases risk of mutations
Chemical carcinogens
single-nucleotide substitutions
Radiation
DNA strand breaks, nucleotide cross-links, abnormal recombination, and chromosomal translocation
Oncogenic viruses
Viruses leading to transformation of human cells (15%)
Epstein Barr
Infection of B cells induces proliferation. If the dividing B cells are not quickly cleared by the immune response, they can acquire mutations that lead to malignant transformation and cancer.
HPV makes proteins that do what to abrogates tumor suppressor function, facilitating proliferation of the virus-infected epithelial cells?
bind to the p53 and Rb tumor suppressor proteins in the infected epithelial cells
Hep B
Hepatocellular carcinoma (SE Asia, tropical africa)
Papillomavirus (many distinct strains)
Genital warts (benign)
Carcinoma of uterine cervix
Epstein Barr Virus cancers
Burkitt’s lymphoma (cancer of B lymphocytes)
Nasopharyngeal carcinoma
B-cell lymphoproliferative disease
Epstein Barr Areas of high incidence
West Africa
Papua New Guinea
Southern China
Greenland (Inuit)
Immunosuppressed or immunodeficient patients
Essential characteristics of cancer cells
Stimulating their own growth
Ignoring growth-inhibiting signals
Avoiding death by apoptosis
Developing a blood supply: angiogenesis
Seeding from site of origin to invade other tissues: metastasis
Constant replication to expand the tumor-cell population
Evasion and outrunning the immune response
How are cancer cells able to evade the immune response?
must proliferate at a greater rate than their rate of elimination by the human immune response
high incidence of cancer among transplant patients taking immunosuppressive drugs provides indirect evidence that
T cells of healthy individuals can recognize and eliminate tumor cells
neoantigens, or cancer neoantigens
peptide antigens recognized by such T cells, in complexes with HLA class I
What leads to CD8 T cell dsyfunction?
When cancer progresses to the point at which tumors are detectable and disseminating, the cytotoxic T-cell response can no longer control the proliferating tumor cells.
T-cell exhaustion
persistence of antigen and inflammation
T cell exhaustion is associated with
progressive loss of effector functions, a distinctive pattern of gene transcription, including the expression of several inhibitory receptors and a metabolic change from glycolysis to oxidative phosphorylation
Which gene codes for the most CT antigens?
Of the 90 different genes that encode CT antigens, approximately half of them are on the X chromosome.
Of the 90 different genes that encode CT antigens, approximately half of them are on the X chromosome.
Changes in the cell-surface expression of MHC class I and in the peptides it binds are detected by
NK cells and CD8 T cells
Intravesicular BCG therapy
Mycobacterium bovis cells are introduced into a patient’s bladder through a catheter. The active adjuvant in this treatment is the mycobacterial DNA, which contains unmethylated CpG, the ligand for TLR9. γδ T cells expressing TLR9 and secreting IL-17 are implicated in mediating the antitumor response.
Study of the cytotoxic T-cell response to EBV identified 19 distinctive peptide antigens that derive
EBV BZL1F1 protein (which initiates the lytic cycle and the release of infectious virus), each being presented by one of 3 HLA-A, 11 HLA-B, and 3 HLA-C allotypes.
Which type of tumour antigen is present only on tumour cells?
Tumour-specific (neoantigens)
Which type of tumour antigen is present on tumour cells and also on some types of normal cell, often at relatively low level?
Tumour-associated antigens
Tumor-specific T cells recognize which antigens?
tumor-specific peptides presented by HLA class I and class II.
Where are tumour specific peptides derived?
viral proteins, cellular proteins such as p53 that contain a tumor-specific mutation, or from amino acid sequences spanning tumor-specific recombination sites
Peptides containing the mutations in p53 and other self proteins are bound by what?
HLA class I and class II and presented to CD8 or CD4 T cells, respectively
What is a feature of 95% of CML have?
chromosomal rearrangement that fuses part of the kinase-encoding BCR gene on chromosome 22 with part of the ABL proto-oncogene on chromosome 9
The novel protein encoded by the fusion gene in CML is necessary for?
progression to leukemia and is also a source of peptide neoantigens that are presented by HLA class I to CD8 T cells
Cancer stem cells
one of a minority population of cells in a tumor that are self-renewing and more resistant to the cytotoxic drugs and radiation that are commonly used to treat cancer
HPV
small 8-kilobase DNA genome encoding eight proteins.
What are the two structural proteins in the HPV genome?
L1 and L2
What are the 6 non-structural proteins function in HPV genome?
E1, E2, E4, E5, E6 and E7
Which one of the following is not a non-structural proteins in HPV?
a. E1
b. E2
c. E3
d. E4
e. E5
f. E6
g. E7
c
What do the structural and non-structural proteins do in HPV genome?
function in viral replication and subversion of host defense mechanisms
During persistent infections what happens with infected HPV cells?
some infected cells integrate HPV DNA into their genomes and selectively express the viral E6 and E7 proteins.
What does E6 bind to and inactivate?
p53
What does E7 bind to and inactivate?
Rb
Inactivation of p53 and Rb leads to what?
allows the infected cells to acquire and accumulate mutations, which over years or decades can eventually lead to malignant transformation and cancer
How many of the 100 different HPV genotypes infect genatalia?
30
The immune response to natural HPV infection is directed toward what?
Variable regions in L1
What is the viral component of the HPV vaccine?
synthetic L1 protein
Purpose of synthetic L1 protein?
spontaneously assembles to give noninfectious particles that in structure and appearance resemble the natural virus
What is the bivalent vaccine an derivative of?
endotoxin
What does the endotoxin in the bivalent vaccine bind to?
TLR4 and activates innate immunity
Which HPV vaccine is given to men and women?
tetravalent
What HPV vaccine is given to women only?
bivalent
When are HPV vaccines given?
vaccine given even if someone is infected, as it can prevent infection by other serotypes
Females not usually infected with how many targeted strains of HPV?
not usually infected with all four of the targeted strains
Current immunisation HPV
three immunizations over a 6-month period for females aged 11–26 years and males aged 13–21 years
How many times greater is the HPV specific antibody response to a natural infection?
80- to 100-fold greater
A clone of CD8 T cells was isolated from a melanoma patient and shown to
recognize a nonamer peptide derived from a melanocyte glycoprotein and presented by HLA-A*32:01.
The sequence of the peptide does not correspond to a contiguous sequence in the melanocyte glycoprotein but is a fusion of residues 40–42 with residues 47–52. This chimera was generated in the proteasome by the process of peptide splicing during the proteolytic degradation of the glycoprotein
When epithelial cells become transformed, they increase the amount OF WHAT?
MIC stress proteins on their surfaces
wHAT DO mic GLYCOPROTINS DO?
ligands for the activating NKG2D receptor
What expresses NKG2D?
NK cells and γδ T cells
T-cell exhaustion _____. (Select all that apply.)
occurs during chronic viral infections, such as hepatitis C
results from the interaction between PD-1 and PD-L1
helps promote the removal of cancer cells by CD8 T cells
cannot be addressed by current immunotherapies for cancer
may occur when CD8 T cells target tumor-specific antigens
results from the interaction between CD28 and B7
a, b, e
Which of the following statements is not true with reference to human papillomaviruses (HPVs)?
a. HPV causes genital, anal, mouth, and throat cancers and genital warts.
b. There are more than 100 different genotypes of HPV, but vaccines are made against only two (bivalent) or four (quadrivalent) genotypes.
c. HPV has a small DNA genome.
d. HPV encodes E6 and E7 proteins, which incapacitate p53 and Rb; over time this may cause malignant transformation.
e. About 95% of HPV-infected individuals make antibodies against the variable region of the L1 viral capsid protein.
f. HPV vaccines are ineffective in individuals who have an established infection.
e
When primary tumor cells are transplanted from a donor to an MHC-incompatible recipient, which of the following is likely to occur?
a. The recipient’s somatic cells become malignantly transformed.
b. A secondary localized tumor develops in the recipient at the site of transplantation.
c. The recipient’s alloreactive T cells kill the tumor cells.
d. Cancer stem cells in the transplant remain quiescent with the potential to reactivate if the recipient becomes immunocompromised.
e. Serum proteases in the recipient cleave MIC from the surface of the tumor cells, enabling these cells to evade immune detection.
c
All of the following are examples of how tumors or the microenvironment in which they develop suppress immune responses except _____.
a. induction of T-cell anergy
b. peptide splicing of self proteins
c. cleavage of MIC glycoproteins from tumor-cell surfaces
d. TGF-β–induced recruitment of regulatory T cells
e. release of TGF-β and IL-10 by regulatory T cells
b
Note 
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