Brainscape's Knowledge GenomeTM

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


See full index

Microbiology & Immunity > 26- Anti-Tumour Immunity and Immunotherapy for Cancer > Flashcards

26- Anti-Tumour Immunity and Immunotherapy for Cancer Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

characteristics of cancer cells

A

rapid uncontrolled growth
increased motility and invasion into tissue
evading immune system
metastasis

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

relationship between the immune system and cancer?

A

imbalance in the immune system affects the development of tumours and prognosis – e.g. immunodeficiency, inflammatory conditions = increase tumour development

immune system can defend against cancer – CD8+ T cells generate to fight specifically against the tumour antigens against your body, but ineffective against the same tumour type from another source due to different antigens

CD8+ T cells can be protective against tumour growth, forms immunological memory against specific tumour antigens

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

what is immunosurveillance/ immunoediting?

A

process where the immune system recognises cancerous/ pre-cancerous cells, leads to their elimination before they can cause damage

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

what are the three phases for tumour immunosurveillance?

A

elimination
equilibrium
escape

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

describe the elimination phase of tumour immunosurveillance

A

immune system detects danger signals - e.g. MIC A/B)/ tumour antigens

DCs and macrophages present tumour antigens to naïve T cells in lymph nodes
activates innate and adaptive immune responses

tumour specific CD4+ & CD8+ T cells are activated to kill the tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

describe the equilibrium phase of tumour immunosurveillance

A

incomplete elimination, some tumour cells remain dormant and modulate tumour antigen expression & stress signals to evade immune detection

immune system eliminates the tumour cells it does detect to reduce tumour antigen - exerts a selection pressure, survival of the fittest of tumour cells that evade immune system detection

contributes to tumour heterogeneity and development of escape mutants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

describe the escape phase of tumour immunosurveillance

A

if immune system is compromised/ imbalanced = escape mutants take advantage

escape mutants emerge from dormancy and contribute to tumour development and progression - increase expression of danger signals and tumour antigens

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

examples of tumour associated danger signals

A

MIC A/B
ULBP
tumour antigens

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

type 1 interferons in cancer immunomodulation

A

produced as an innate response by virally infected ells - tumour cells can induce viral detection pathways through type 1 IFN production

upregulates MHC molecules, increases tumour antigen presentation = stimulates T and B cells

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

BCG in cancer immunomodulation

A

lie attenuated M. bovis organism used against bladder cancer cells

activates immune response:
1. BCG binds to TLRs 2 & 4 = activates DCs =
increase tumour antigen presentation to naïve T cells
2. activates NK cells, produce cytokines which activate T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

IL-2 in cancer immunomodulation

A

T cell growth factor for T cell survival, growth, activation and proliferation

toxic in high doses, sometimes used with GM-CSF OR infused in LAK cells ex vivo and then re-inserted into patient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

GM-CSF in cancer immunomodulation

A

granulocyte macrophage colony stimulating factor

stimulates APCs, increases tumour antigen presentation to T cells

sometimes used with IL-2 for T cell activation and proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Trastuzumab - mechanism?

A

targets ERBB2 on breast cancer cells, blocks signalling

promotes tumour cell killing = allows NK targeting of tumour cells and killing via ADCC

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

Avastin/ Bevacizumab - mechanism?

A

targets VEGF (vascular endothelial growth factor) and blocks signalling for angiogenesis = kills tumour cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Rituximab - mechanism?

A

anti-CD20 antibody

binds against CD20+ non-Hodgkin’s lymphoma B cells and induces apoptosis

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

Alemtuzumab/ Campath - mechanism?

A

anti CD52 antibody

binds to CD52 on B cells involved in chronic lymphocytic lymphoma, induces apoptosis

however it does bind to all B cells with CD52 and depletes B cell population, affects immune responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Ipilimumab

A

anti CTLA-4 antibody = blocks downregulation of T cell activity by blocking CTLA-4 binding, allows T cell to prolong activity

however CTLA-4 is important for immune system regulation – non-specific actions of anti-CTLA4 may lead to autoimmunity
- non-specific action = can affect lots of T cells

18
Q

different methods of immune mediated tumour cell killing with antibodies?

A

antibody binds to specific tumour antigen, forms a complex with Fc region sticking out - triggers:

  1. NK cell activation & ADCC = CD16 receptor on NK cells binds to Fc region - release of cytotoxic granules
  2. complement cascade activation via classical pathway = MAC formation
  3. phagocytosis via macrophage Fc receptors binding to Fc region
  4. antibodies bind to both T cells and tumour cells = enhances T cell recognition of tumour antigens independent of MHC presentation
  5. anti-CTLA4 antibody prevents T cell downregulation, prolongs activity
19
Q

different methods for direct tumour cell killing via antibodies?

A
  1. antibodies bind to tumour cell surface receptors = prevent signalling for tumour cell survival and proliferation
  2. antibodies inhibit enzymes involved in key metabolic processes needed for survival
  3. antibodies conjugated with cytotoxic drugs or toxins - selective killing with direct delivery of drugs to tumour cells with complementary antigens
  4. antibodies act as receptor agonists, activate tumour cell apoptotic pathways
20
Q

how are antibodies involved in vascular and stromal cell ablation of tumours?

A

antibodies break down blood vessels tumour needs for growth & removes tumour cell-stromal contact so tumour has nowhere to attach to and no blood supply = dies

21
Q

different methods for delivering antibody therapies

A

anti-CD20 antibody/ ibritumomab - delivers radiotherapy to CD20 B cells in non-Hodgkin’s

anti-CD30 antibody delivers Aurostatin toxin to CD30+ B cells

Ontak is IL-2 = delivers diphtheria toxin in T cell lymphoma

22
Q

anti-PD1 antibodies - mechanism?

A

anti PD-1 antibodies for PD-1 receptor on T cells - prevent PDL-1 on tumour cells binding and inducing T cell apoptosis

T cells survive and continue attacking tumour

sometimes combined with anti-CTLA4 antibodies (ipilimumab) = reduce conc of antibodies needed for treatment, reduce side effect

23
Q

examples of PD-1 antibodies

A

Nivolumab
Pembrolizumab

24
Q

method for therapeutic vaccination/ using DCs in cellular cancer therapy

A

patient blood sample is taken and monocytes are isolated - exposed to GM-CSF & IL-4 and generated into immature DCs

immature DCs loaded with tumour antigen from isolated tumour cells/ peptide presentations/ tumour cell lines

immature DCs are matured with tumour antigen exposure and activation of TLRs

inserted back into patient via vaccination - mature DCs present tumour antigen to T cells = generates anti-tumour T cells

25
Q

what are TILs/ tumour infiltrating lymphocytes?

A

primary T cells that have migrated into tumours and can recognise & kill tumour antigens

26
Q

significance of TILs in tumour?

A

more TILs and CD8+ T cells in tumour = better prognosis

27
Q

how are TILs involved in cellular cancer therapy? - method?

A

assuming that TILs are present in the tumour but not working well - adoptive cell therapy with TILs

T cells from tumour are extracted

in culture - exposed to IL-2 and anti-CD3 for polyclonal stimulation and expansion in vitro

lymphodepletion depletes patient’s existing T cell population = creates amore favourable environment for the activity of transferred TILs

stimulated T cells are reinserted with enhanced activity against tumour cells

28
Q

disadvantage of adoptive TIL cellular therapy?

A

need a big enough tumour to extract TILs present

culture can take too long (may be too late for patient)

culturing can reduce the quality of T cells, leads to a high rate of failure

29
Q

what are LAK cells?

A

lymphocyte associated killer cells

30
Q

how are LAK cells involved in cellular cancer therapy? - method?

A

PBMC cells are isolated from a blood ample and cultured with IL-2

culture produces NK-T, NK and T cells with high anti-tumour activity which can target & kill the tumour

NK cells are the main type of LAK cell - recognise and kill cells with MHC downregulation - e.g. tumour cells - through antibody-dependent cellular cytotoxicity and release of lytic granules

31
Q

how do NK-T cells recognise foreign/ non-self cells?

A

recognise lipid antigens, triggers NK-T cell activation and proliferation - no MHC or peptide-antigen recognition

produce cytokines & activate immune responses against target cells

32
Q

how are NK-T cells involved in cellular cancer therapy? - method?

A

NK-T cells are expanded using alpha-galactosyl ceramide pulsing DCs

increases endogenous NK-T population = increases immune response against tumour cells & production of cytokines which modulate anti-tumour activity

33
Q

how are gamma-delta T cells involved in cellular cancer therapy? - method?

A

gamma-delta TCRs/ T cells detect stress molecules on the surface of tumour cells- e.g. MIC A/B

activates anti-tumour activity

34
Q

how are dendritic cells involved in cellular cancer therapy? - method?

A

involved in cancer vaccination - from blood sample, immature DCs are exposed to tumour antigens which activates their TLRs, making them mature DCs

mature DCs are inserted into patient via a vaccine - present tumour antigens to T cells and activate anti-tumour activity `

35
Q

what is a CAR/ chimeric antigen receptor?

A

a recombinant receptor that redirects specificity and activity of immune cells to one single molecule - e.g. tumour antigens

36
Q

how are chimeric antigen receptors involved in cellular cancer therapy? - method?

A

CARs have an antigenic recognition domain, and a cytoplasmic tail with multiple signalling domains to activate T cells

allow for high specificity and affinity of immune cells to a range of tumour antigens without MHC restriction

37
Q

disadvantages of CAR therapy?

A

links to autoimmunity

38
Q

how is adoptive cellular therapy applied with PBMC T cells?

A

PBMCs are isolated from a blood sample and stimulated with:
- IL-2
- tumour antigens
- autologous dendritic cells

clonal expansion of T cells that response to certain tumour-associated antigens

genetically engineered TCRs with high affinity for a range of commonly expressed tumour associated antigens (TAAs) are also transduced into T cells and reinfused back into patient

39
Q

examples of commonly expressed TAAs?

A

gp-100
p53
MART-1

40
Q

advantages of adoptive cellular therapy with T cells & TCR transduction?

A

patient specific
remain in blood for approx. 1 yr

41
Q

disadvantages of adoptive cellular therapy with T cells & TCR transduction?

A

low success rate
TAAs must be present in patient’s tumour
must match epitopes to patient HLA = risk rejection of cultured immune cells otherwise

Microbiology & Immunity (37 decks)

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