Mid 1: Lec 8

Question 1

TNF alpha protein type and what system cells does it regulate

Answer 1

cytokine signalling protein, primary reg of immune system cells

Question 2

TNF alpha specific effects (symptoms and pathways)

Answer 2

Pyrogen (fever inducing)

apoptosis (caspase mediated)

Activation of NF-KB tf involved in inflammatory response and cell regulation

Activation of MAPK pathways (immediate-early response
to stress)

Cytotoxic

Question 3

Where is TNFa secreted from

Answer 3

macrophages and other cell types

Question 4

TNFa production and maturation

Answer 4

produced as cell membrane protein, matures once it is cleaved

Question 5

TNFa receptors and associated proteins

Answer 5

TNFR1 and TNFR2

associated with protein complex that includes adaptor protein TRADD

Question 6

allergic respitory disease: symptoms, type of molecule interactions

Answer 6

complex cytokine interactions, airway
inflammation, reduced breathing ability,
and airway remodeling in response to
allergens

Question 7

Mild-Moderate asthma proteins/cells involved and treatment options

Answer 7

involves Th2 lymphocytes, eosinophils, and
high levels of IgE

Treatable by corticosteroids

Question 8

Severe Refractory Asthma proteins/cells involved and treatment options

Answer 8

involves Th1 lymphocytes, Th17
lymphocytes, neutrophils and some
eosinophils, and TNF-α

– Not treatable by corticosteroids

Question 9

Effects of TNFa during asthma

Answer 9

recruitment of proinflammatory cells and affected airway
remodeling

Question 10

TNFa role in influenza

Answer 10

required for clearing influenza from infected lung

Question 11

NF kapa B module: protein type, signalling module pieces and reason for functional pleiotropism

Answer 11

NF kapa B: inflammatory tf

Inhibitor of NF- kapa B (I kapa B)

I kapa B kinase (IKK)

reason: responsiveness of IKK to diverse signals

Question 12

IKK signalling pathway: players, Nf kapa B control type

Answer 12

LPS (endotoxin), TNFa are signalling molecules for this path

TNFa leads to production of A20 which decreases TNFa production through negative feedback

LPS leads to increased TNFa

all is mediated through NF kapa B which mediates “feed forward mechanisms” that produce positive feedback on IKK activity

Question 13

NF kapa B single cell microscopy exp

Answer 13

measured NF kapa B at different TNFa concentrations

fluorescent fusion protein used to visualize movement of NF kapa B

NF kapa B transported in and out of nucleus in characteristic oscillations in response to TNFa

Effect of TNFa on gene transcription is different for different concentrations.