Inflammation

Question 1

What does inflammation protect against?

Answer 1

Infectious agents.

Question 2

What is the role of the epithelium in inflammation?

Answer 2

Proliferation, to repair damaged barrier

Question 3

What is the role of the endothelium in inflammation?

Answer 3

Angiogenesis and vasodilation to increase blood flow, increased vascular permeability to provide serum/nutrients for repair.

Question 4

What is the role of fibroblasts in inflammation?

Answer 4

Repair the structure of the damaged tissue.

Question 5

What is the role of leukocytes in inflammation?

Answer 5

Detect damage/infection, initiate inflammation and direct inflammation type, destroy pathogen, regulate other tissue cells, stimulate tissue repair, direct resolution of inflammation.

Question 6

What detects pathogen-associated molecular patterns (PAMPs)?

Answer 6

Toll-like receptors (TLRs)

Question 7

What are host molecules released from damaged/stressed cells called?

Answer 7

Damage-associated molecular patterns (DAMPs)

Question 8

What detects DAMPs?

Answer 8

TLRs

Question 9

What does TLR stimulation induce?

Answer 9

Cytokine and chemokine production and cell differentiation (e.g. dendritic cells).

Question 10

What do TLRs require for signal transduction?

Answer 10

MyD88

Question 11

What do TLRs, DAMPs, PAMPs and other pattern recognition receptors (PRRs) do?

Answer 11

Initiate and potentiate inflammation, influence adaptive responses.

Question 12

What do cytokines do?

Answer 12

Regulate broad aspects of leukocyte function and differentiation.

Question 13

What do chemokines do?

Answer 13

chemoattractans: recruit leukocytes into tissues and control their localisation.

Question 14

Which cells mediate adaptive immunity?

Answer 14

T and B cells.

Question 15

What do T cell receptors and B cell receptors recognise?

Answer 15

Antigens

Question 16

Which antigens do T cell receptors recognise?

Answer 16

Protein derived antigens presented in the context of MHC molecules on the surface of antigen presenting cells.

Question 17

What is an antigen?

Answer 17

Any substance that can be recognised by a TCR and/or a BCR. Host-derived or pathogen-derived.

Question 18

What happens to lymphocytes that recognise self antigens?

Answer 18

They are destroyed or converted into regulatory T cells. This prevents autoimmune disease.

Question 19

What do dendritic cells do?

Answer 19

Pick up and present antigens.

Question 20

Which type of T cells are CD4+ cells?

Answer 20

Helper T cells.

Question 21

Which type of T cells are killer cells?

Answer 21

CD8+ cells.

Question 22

How does T cell priming work?

Answer 22

Dendritic cell activates CD4+ T cells
CD4+ T cells license the dendritic cells.
Dendritic cell then primes CD8+ T cells.

Question 23

What do Naiive B cells become?

Answer 23

Memory B cells or plasma B cells.

Question 24

What does the germinal centre reaction do?

Answer 24

Increase affinity for antigen.

Question 25

What percentage of cancer deaths are linked to pre-existing infection or inflammation?

Answer 25

15-20%

Question 26

Which pro-tumorigenic processes occur in chronically inflamed tissue?

Answer 26

``` Continuous tissue damage and repair. Hyperproliferative epithelilum. Hypoxia disrupts DNA repair. Inhibition of p53 activity. Mutagenic products from leukocytes. Extensive angiogenesis. Protease remodelling of the stroma. Release of stromal growth factor stores. ```

Question 27

What is MyD88 required for?

Answer 27

Signalling through most TLRs, and IL1R.

Question 28

Which molecule is required for liver tumorigenesis?

Answer 28

MyD88

Question 29

How does the immune response control early tumours?

Answer 29

NK cells recognise and attack early tumour cells. NK cells and other effectors recruited to site by chemokines. Dendritic cells head for the lymph node carrying tumour antigens. Dendritic cells activate tumour specific T cells which home to tumour site. Cytotoxic T cells and Th1 (CD4). Along with macrophages these cells help to eliminate tumour cells.

Question 30

What are the three Es of tumour immunoediting?

Answer 30

Elimination Equilibrium Escape

Question 31

What are the 6 hallmarks of cancer?

Answer 31

``` Tissue invasion and metastasis. Evasion of apoptosis. Sustained angiogenesis. Limitless replicative potential. Self sufficiency in growth signals. Insensitivity to growth inhibitors. ```

Question 32

Give three examples of evidence of cancer-associated inflammation.

Answer 32

1. Inflammatory leukocytes in all tumours from very early stages. 2. Tumours constitutively produce cytokines, chemokines, DAMPs and other pro-inflammatory molecules. 3. Oncogene activation can induce inflammatory programmes.

Question 33

What controls leukocyte migration?

Answer 33

Chemokines.

Question 34

In tumours what causes chemokine receptors to be switched on?

Answer 34

Hypoxia.

Question 35

What does TAM stand for?

Answer 35

Tumour-associated macrophages.

Question 36

What kind of prognosis does a high number of TAMs correlate with?

Answer 36

Poor prognosis.

Question 37

In what way can TAMs help tumour growth?

Answer 37

Stimulate cell proliferation and angiogenesis. | Can make immunosuppresive molecules (IL-10, TGFβ).

Question 38

What does VEGF do?

Answer 38

Induce angiogenesis.

Question 39

What happens to the macrophages as the tumour progresses?

Answer 39

They polarise.