Lecture 11

1.
How does chronic inflammation arise? (3)
"Persistant exposures, abnormal immune responses, novel cells"
2.
How do persistent exposures induce chronic inflammation? (2)
"Irritants (smoking, bronchitis), microbes (TB, HBV, H. pylori)"
3.
How do abnormal immune responses give rise to chronic inflammation? (3)
"Allergies, innocuous commensal microbes (Chron’s), self attack (rhuematic fever, autoimmune diseases)"
4.
How do novel cells give rise to chronic inflammation? (2)
"Wounds that do not heal (cancers), transplants (rejection)"
5.
How can stress cause low grade inflammation?
"Noradrenaline generates TNF, IL-1beta, IL-6"
6.
How can inactivity cause low grade inflammation?
Exercise suppresses inflammaotry cytokines
7.
How can diet reduce low grade inflammation?
Fermentation of plant fibre > production of short chain fatty acids > suppression of inflammation
8.
How can obesity cause low grade inflammation?
"Hypertrophic adipose tissue releases TNF, IL-1beta, IL-6, and saturated fatty acids (TLR activators), necrotic adipocytes release DAMPs."
9.
How do commensal microbes influence the level of inflammation?
Symbionts promote Tregs
10.
Which system is acute inflammation mediated by?
The innate immune system (neutrophils and macrophages/monocytes)
11.
How do innate cells mediate inflammation?
"Phagocytose debris, lipoprotein, bacteria, kill microbes, release TNF, IL-1beta, IL-6, MMps, ROS"
12.
How is chronic immunity mediated?
Adaptive immune lymphocytes
13.
What cytokines do Th1 cells release?
Interferon (IFN) gamma
14.
What does IFN-gamma do?
Stimulates Th1 develpment and macrophage responses to intracellular pathogens.
15.
What does an abnormal response to IFN-gamma result in?
Autoimmune disease
16.
What cytokines do Th2 cells release?
IL-4
17.
What does IL-4 do?
Stimulates Th2 development and eosinophil responses to helminths (worms)
18.
What does an abnormal response to IL-4 result in?
Allergy
19.
What cytokines do Th17 cells secrete?= ="IL-17, IL-21"
20.
What do IL-17 and IL-21 do?
"Stimulate Th17 development (IL-21), epithelial responses to microbes (secretion of antimicrobial peptides, Granulocyte Macrophage-Colony Stimulating Factor -> neutrophil recruitment)"
21.
What do abnormal responses to IL-17 and IL-21 result in?
Autoimmune diseases
22.
What do Treg cells secrete in response to antigen presentation by APCs?
"TGFbeta, IL-10"
23.
What does TGF-beta do
"Development of Treg cells, suppression of inflammation"
24.
What does a deficiency in TGF-beta result in?
Excessive inflammation
25.
What are the types of macrophage granulomas?
"Foreign body granulomas, immune granulomas"
26.
Describe the Mtb infection process?
"Inhalation of Mtb bacteria in droplets, alveolar macrophages phagocytose Mtb, migration to lymph node, activation of Th1 cells, Th1 cells migrate to lungs release IFN-gamma, Mtb lipids inhibit macrophages and generate permissive macrophages, intracellular proliferation, Neutrophils release ROS, TNF causing apoptosis and necrosis releasing Mtb spreading infection"
27.
How does Mtb become latent?
"Th2 cells release IL-4 generating fibrosis impeding Th1 cells. Caseous necrosis accumulates, Mtb adopts biofilm and becomes latent"