Brainscape's Knowledge GenomeTM

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


See full index

Principles of tumour biology for FRCR CO1 > 1.5 The role of the immune system > Flashcards

1.5 The role of the immune system Flashcards

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

What is immunoediting?

A

The immune system can either constrain or promote tumour development

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

What are the three phases of immunoediting?

A
  1. Elimination
  2. Equilibirum
  3. Escape
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What occurs during Elimination?

A

Immune surveillance - the immune system detects and destroys emerging tumour cells - if successful this prevents cancers from growing.

Innate immunity: Natural killar cells and macrophages recognise and kill stressed or abnormal cells

Danger Cytokines release: pro-inflammatory cytokines like interferon-gamma enhance immune cell activity. Cytokines such as interfero alpha and Heat shock proteins cause activation and maturation of dendritic cells.

Adaptive immunity: dendritic cells present tumour antigens to CD4+ and CD8+ T cells - which are activated to target and eliminate the tumour cells

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

How is Interferon Gamma released?

A

MHC class I bind to NKG2D releasing interferon gamma

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

What occurs during Equilibrium?

A

If some tumour cells survive Elimination, the immune system enters a state of balance with the tumour that can last for decades

Tumour cell dormancy: some tumour cells enter a non-proliferative state, evading the immune system while remaining viable

Angiogenic dormancy

Immune pressure: cytotoxic T cells and NK cells exert selective pressure, they keep tumour gorwth in check but don’t completely eradicate the cells

Genetic instability: under the pressure of the immune system tumour cells accumulte mutations which start to allow them to evade the immune response (resistant clones)

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

What occurs during Escape?

A

Tumour cells can now evade the immune system and proliferate unchecked, the immune system can no longer control tumour growth, leading to tumour expansion and metastasis, clinically detectable cancer arises.

Immune suppression: tumour cells can start to secrete immunosuppressive molecules like TGF-B or recruit regulatory T cells (Tregs) to inhibit immune repsonses

Down regulation of tumour antigens: tumour cells can lose or alter their expression (don’t load them into MHC1) of antigens, making them unrecognisable to T cells

Up regulation of host antigens: become invisible to immune system

Checkpoint activation: tumours can exploit immune checkpoint pathways e.g. PD-1 or PD-L1 to suppress T cell acitivity

Apoptosis of T cells: Fas ligands on tumour cell surface bind to Fas receptors on CDG8 T cells and cause apoptosis of T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the key features of the innate immune system?

A
  1. First line of defence
  2. Essenntial for survival
  3. No memory
  4. Fascilitates activation of the adaptive immune response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are they key cells of the innate immune system?

A
  1. WBCs aka Granulocytes e.g. Neutrophil, Basophil, Eosinophil
  2. Macrophages
  3. Dendritic cells
  4. Phagocytes
  5. Natural Killer cell
  6. Mast cell

and
Complement proteins

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

What are the main antigen presenting cells of the innate immune system?

A
  1. Dendrtitic cells
  2. Macrophages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do dendritic cells do?

A
  1. Main antigen presenting cells
  2. Secrete and respond to cytokines and chemokines: -
    - they secrete cytokines - promote or express inflammation e.g. IL-12, IL-6, TNFa
    - they secrete chemokines - attract other immune cells e.g. T, B, NK to the site
    - they respond to cytokines for cell maturation, migration, and function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do Natural Killer cells do?

A

Default position is activated

They act as a back-up mechanism when viruses or tumour cells downregulate MHC antigen presenting to avoid recruitment/activation of T cells

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

What are danger signals?

A

Pathogen Associated Molecular Patterns (PAMP)
and
Damage Associated Molecular Patterns (DAMP)

They alert immune cells to the presence of infection, tissue damage, and stress.

  1. These are recognised by Toll-like receptors
  2. Toll like receptors stimulate the NFkB pathway
  3. NFkB pathway activates cytolines and co-stimulatory molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are PAMPs?

A

Molecules derived from pathogens e.g. bacterial lipopolysaccharides (LPS), viral RNA, fungal Beta-glucans

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

What receptors recognise PAMPs?

A

Pattern Recognition Receptors (PRRs)

Toll-like receptors (TLRs) - which are on the surfaces of macrophages, dendritic cells, and neutrophils

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

What are DAMPs?

A

Molecules released from damage or stressed cells e.g. ATP, mitochondiral DNA

Recognised by PRRs and TLRs which are on the surfaces of macrophages, dendritic cells, and neutrophils

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

What are the key features of Adaptive immunity?

A
  1. Slower response
  2. Memory
  3. Clonality - able to make lots of the same cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the cells in Adpative immunity?

A
  1. B cell - produce antibodies
  2. T cell - CD4+ and CD8+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What cells are involved in both innate and adaptive immunity?

A

gamma6 T cell

Natural killer T cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do B cells cause phagocytosis of bad cells?

A
  1. B cells produce antibodies
  2. Antigens binds to the antibodies
  3. B cell is activated
  4. B cell turns into a plasma cell
  5. Floods bad cell with antibiodies
  6. Opsonisation occurs - immune system identifies as bad
  7. Phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are T cells?

A
  1. Produced in the bone barrow
  2. Mature in the thymus - ‘educated’
  3. T cell receptors recognise specific MHCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the 4 types of T cells?

A
  1. Helper CD4+
  2. Cytotoxic CD8+
  3. Regulatory (Tregs)
  4. Memory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What to Helper T cells (CD4+) do?

A

Produce cytokines that
- promote CD8+ e.h. IL12
- B cell activation and function e.g. IL4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What do Regulatory T cells (Tregs) do?

A

CD4+, CD25+, FOXP3+

Suppress immune responses to maintain tolerence of CD8+ and prevent autoimmunity

Release factors e.g. TGF-B or by cell-cell contact e.g. CTLA-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What do Cytotoxic T cells (CD8+) do?

A

Identify and kill infected, damaged, or cancerous cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What do Memory T cells do?

A

Provide long-term immunity by ‘remembering’ past infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How are T cells activated?

A

Antigens are presented by antigen presenting cells (APCs) binding the antigen to MHCs on their surface

28
Q

What are antibodies?

A

a.k.a Immunoglobulins

Antibodies recognise antigens on the pathogen

29
Q

What is the structure of an antibody?

A

4 polypeptide chains
2 x heavy
2 x light

Y shape

30
Q

What are tumour associated antigens?

A

Antigens (proteins) expressed on surface of tumour cells (and normal cells in lower concentrations) that can be recognised by the immune system and trigger antibody response and recruiting T cells

Some are Oncofetal e.g. alpha-foeto protein (AFP) and Carcinoembryonic antigen (CEA)

Some are differentiation e.g. MART-1 in melaboma

Some are mutated e.g. p53 mutations

31
Q

What are the Class 1 Major Histocompatibility Complexes?

A

HLA - A, B and C

Human Leukocyte antigen

32
Q

How long are the MHC Class 1 peptides?

A

Short (8-12 amino acids)

33
Q

What do MHC Class 1 bind to?

A

Intracellular peptide antigens

34
Q

What cells do MHC Class 1 present their antigens to?

A

CD8+ T cells only

35
Q

What cells express MHC Class 1?

A

Basically all cells with a nucleus

36
Q

What are the Class 2 Major Histocompatibility Complexes?

A

HLA
- DP
- DQ
- DR

37
Q

How long are the MHC class II peptides?

A

Long (12-24 amino acids)

38
Q

What do MHC Class II bind to?

A

Extracellular peptide antigens that have been phagocytosed

39
Q

What cells do MHC Class II present to?

A

CD4+ T cells only

40
Q

What cells express MHC Class II?

A

Antigen presenting cells only

APCs can also load exogenous antigens onto MHC Class I to present to CD8+

41
Q

How are T cells activated?

A
  1. T Cell Receptor (TCR) binds to specific antigen presented on the MHC (CD8+ Class I, CD4+ Class II)
  2. Co-stimualtion - a second signal is recuired to ensure T cells are activated only when danger cells are pesent - e.g. CD28 on the T cell binds to B7 molecule (CD80/86) on the APC

If both signals are present T cells are activated - they proliferate (clonal expansion) and differentiate (become cytotoxic, helper, memory)

Cytokines - interleukins and TGF-B e.g. IL3 amplify acitvation and proliferation

42
Q

What do activated T cells release?

A

Granzyme A and B
Perforin

43
Q

What is Immune tolerence?

A

The ability of the immune system to recognise and avoid attacking self and harmless antigens such as food proteins on commensal microbes.

Prevents autoimmunity and hypersensitivity.

44
Q

What is Central immune tolerence?

A

Occurs during the development of T cells in the Thymus and B cells in the bone marrow

Lymphocytes against self undergo apoptosis or modified into regulatory T cells before entering the circulation

45
Q

What is Peripheral Tolerence?

A

Acts on mature lymphocytes in peripheral tissue to supress self-reactive cells that escaped central tolerence

They do this by:
1. Anergy - functionally inactivate self-reactive lymphocytes
2. TRegs actively suppress immune repsponses to self
3. Immune privilege - certain tissues limit immune access to prevent damage

46
Q

What is the Danger Hypothesis?

A

Theory that proposes that the immune system responds primarily to ‘signals of danger’ aka cell stress or damage (PAMPs and DAMPS), rather than just recognition of ‘self’ vs ‘non-self’

This explains autoimmunity
Tumour immunity - they release DAMPs

47
Q

What is Immunomodulation?

A

Alteration of immune responses so they are enhanced or suppressed

48
Q

How do tumours exploit immunomodulatory mechanisms to evade immune destruction?

A
  1. Manipulate co-stimualtory signals which are required for immune activation e.g. CD28 binding to B7
  2. Enhance negative regulatory pathways that suppress immune responses
49
Q

How to tumours modulate co-stimulation?

A
  1. Downregulate co-stimulatory molecules e.g. B7 on the surface of antigen presenting cells
  2. Suppress antigen presenting cell maturation to prevent effective co-stimulation
50
Q

How do tumour cells cause negative regulation?

A
  1. Immune checkpoints - overexpress PD-L1 (bind to PD1 on APCs and hide via T cell exhuastion due to chronic stimulation ) and secrete more immunosuppressive cytokines
    Recruit:
  2. Tregs
  3. myeloid-derived suppressor cells
51
Q

How do tumours cause immune suppression?

A
  1. Secretion of immunosupressive factors
  2. Upregulation of immune checkpoints
  3. Metabolic supression
52
Q

What Immunosuppressive factors are secreted by tumour cells? What do they do?

A

Cytokines e.g. TGF-B, IL-10 and VEGF

These:
- suppress T cell acitivity
- inhbit dendritic cell maturation
- promote Treg recruitment

53
Q

How do tumour cells upregulate immune checkpoints?

A

Tumour cells express immune checkpoint ligands like PD-L1 which bind to PD-1 on T cells.

When PD-L1 and PD1 interact the tumour remains undetected

Thes inhibit T cell activation and promote T cell exhuastion

54
Q

How do immune checkpoint inhibitors work against cancer?

A

Checkpoitn inhbitors block PD-1 and PD-L1 interactions - the cell becomes visible to the immune system so T cells recognise and destroy it

55
Q

What are some Anti-PD1 immunotherapies?

A
  • Pembrolizumab
  • Nivolumab
  • Cemiplimab
56
Q

What are some Anti-PD-L1 immunotherapies?

A
  • Atezolizumab
  • Avelumab
  • Durvalumab
57
Q

What is an Anti-CTLA-4 immunotherapy?

A

Ipilimumab

58
Q

How can immunotherapies be combined?

A

Combining checkpoint inhbitiors that act at different points in the cancer immunity cycle can be synergisitic

e.g. anti CTLA-4 primes and activates T cells
Anti-PD-1promots T cell killing

e.g. Ipi/Nivo

59
Q

How do tumour cells cause metabolic suppression of the immune response?

A

Alter their microenvironment by depleting nutrients e.g. glucose, tryptophan

Produce lactic acid which inhbit immune cell function

60
Q

What are Tumour Infiltrating Lymphocytes?

A

TILs are immune cells (mostly T cells) that infiltrate the tumour microenvironment

61
Q

What do TILs do?

A

The presence and type of TILs correlate with tumour immunity

CD8+ TILs have effective anti-tumour responses

Exhausted T cells: express immune checkpoint hinhibitors such as PD-1 and are functionally impaired, this means they can’t control tumours

Tumours can suppress or exclude TILs thereby evading the immune system

62
Q

What do Tregs do in tumours?

A

Tregs are immunosuppressive CD4+ T cells that maintain immune tolerence and prevent autoimmunity

High levels of Tregs in the tumour microenvirnoment correlate with poor prognosis as they suppress anti-tumour immunity

In tumours they:
- Suppress effector T cells by secreting cytolines e.g. IL-10, TGF-B
- Inhibit dendritic cell function
- Inhbit cytotoxic T cell activation
- Prompote tolorence in the tumour microenvironment

63
Q

How can tumour immune suppression be targeted therapeutically?

A
  1. Immune checkpoint inhibitors e.g. anti-PD-1 or PDL-1 restore T cell activity (e.g. pembro)
  2. Adoptive T cell therapy (CAR-T)
  3. Treg depletion
64
Q

What is CAR-T therapy?

A

T cells are given synthetic T cell receptors that can bind even if the antigen is not present on the MHC

65
Q

What is T Cell Receptor therapy?

A

Patients with no T cell response to tumours, give T cells new TCRs and re-infuse

66
Q

How can Tumour infiltrating Lymphocytes be a therapuetic target?

A

Harvest them from tumours, activate them and reinfuse

Principles of tumour biology for FRCR CO1 (5 decks)

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