module 05 section 04 (cytokine-related diseases)

Question 1

dysfunction in cytokine signalling can cause:

Answer 1

severe damage to the body - cytokine-related diseases

Question 2

list cytokine-related diseases

Answer 2

bacterial septic shock, lymphoid and myeloid cancers

Question 3

what do patients with bacterial-induced sepsis experience?

Answer 3

fever, weakness and rapid HR/breathing rates

Question 4

what happens in bacterial septic-shock?

Answer 4

• gram neg cell wall endotoxins stimulate the patients macrophages to overproduce IL-1 and TNF-a - resulting in shock state
• these pro-inflamm & pyrogenic cytokines amplify inflamm cascades in an autocrine and paracrine manner - activating macrophages to secrete additional pro-inflamm cytokines (IL-6 and IL-8)
• these, in combination w other molecules secreted by macrophages (lipid mediators and reactive o2/N species) result in fever, diarrhea, organ dysfunction and widespread clotting

Question 5

what is a “shock state” characterized by?

Answer 5

severe hypotension, severe pulmonary edema and hemorrhage

Question 6

infectious bacteria release what during bacterial toxic shock?

Answer 6

superantigens (SAgs)

Question 7

what are SAgs?

Answer 7

class of antigens that cause non-specific activation of T-cells 
(stimulate up to 30% of T-cells compared to normal <0.01%)

Question 8

what results from the SAg activation of T-cells?

Answer 8

cytokine storm within the body

Question 9

what is characteristic of a cytokine storm?

Answer 9

high levels of IL-1 and TNF-a

Question 10

what results in the characteristic symptoms of cytokine storms (fever and swelling)?

Answer 10

high levels of IL-1 and TNF-a

Question 11

provide an example of a pathogen that causes bacterial toxic shock

Answer 11

• Staphylococcus aureus - causes Toxic Shock Syndrome which is often contracted through the prolonged use of tampons or infection following surgery
• SAg = TSST-1 (toxic shock syndrome toxin-1) - exfoliative toxin that causes sloughing of skin

Question 12

(generally) in lymphoid and myeloid cancers, the overproduction of IL-6 leads to what?

Answer 12

exaggerated cell proliferation

Question 13

what does chronic IL-6 signalling result in? where may this occur?

Answer 13

• plasmacytosis

- can occur in the lymph nodes, bone marrow or other tissues, blood or excretions of the body

Question 14

what is plasmacytosis?

Answer 14

condition where there is an unusually large proportion of plasma cells in tissues, blood, or secreted fluids

Question 15

can IL-6 also have internal effects on proliferation of cancerous cells within the body?

Answer 15

yes - in myeloma cells, downstream effects of IL-6 signalling deactivate the critical tumor supressor gene p53

Question 16

describe Chagas disease

Answer 16

• caused by trypanosoma cruzi parasitic infection (kissing bug)
• characterized by immunosupression, swelling and fever
• pathology: suppression of IL-2a receptor expression (i.e. IL-2 is reduced), leads to chronic immune supression that becomes increasingly severe over the years and eventually results in death if left untreated