Lecture 8

1.
What are the cardinal signs of inflammation?
"Heat, redness, swelling, pain"
2.
What does inflammation bring to a site of injury?
"Nutrients, oxygen, exudate (antibodies), leukocytes (defence), phagocytes (cleanup), fibrin mesh"
3.
What does inflammation remove from a site of injury?
"Toxins (via exudate, lymph)"
4.
What are pro inflammatory signals following tissue damage?
"Neurons release peptides, DAMPs, PAMPs (endotoxin, LPS)"
5.
"What are DAMPs, PAMPs sensed by?"
Pattern recognition receptors (PPRs)
6.
What are soluble PRRs?
Complement
7.
What are cell bound PRRs?
Toll like receptors (TLRs)
8.
What cells respond to proinflammatory signals?
"Macrophages, mast cells"
9.
What granule inflammatory mediators do mast cells release on stimulation?
"Histamines, proteases, TNF"
10.
What causes redness and heat in inflammation?
Vasodilation > hyperaemia
11.
What happens in the case of an insect bite?
"Endothelial cells retract, creating gaps (0.1-0.4microns) allowing exudate to pass"
12.
What happens in the case of sever injury?
Endothelial damage leads to their detachment from the basement membrane > leaking until clot or repair takes place
13.
What causes swelling and pain?
"Increased hydrostatic pressure in capillaries, permeability, water binding of exudate proteins > intertitial oedema > stretching of tissue causes pain"
14.
What are vasoactive amines?
Preformed histamine stored in granules of mast cells/basophils/platelets
15.
What are tryptases?
Proteases that cleave protease activated receptors which induces inflammation
16.
How do lipids mediate inflammation?
"Inflammatory signals activate phospholipase A to create lysophophatidylcholine and arachidonic acid
17.
Lysophosphatidylcholine is converted into PAF
which induces platelet aggregation, leukocyte adhesion, chemotaxis and activation. 
18.
Arachidonic acid forms
1. Cyclooxygenases (COX1, COX2) which generate prostaglandins and 2. 5-lipoxygenase which generates leukotrienes."
19.
What do prostaglandins do?
"Vasodilation and platelet disaggregation ( PCI2, PGE2), vasoconstriction and platelet aggregation (TXA2)"
20.
What do leukotrienes do?
"Neutrophil chemotaxis and activation (LTB4), vasopermeability, mucus, bronchconstriction (CysLTC4, D4, E4)"
21.
What are circulating inflammatory mediators?
"Coagulation, fibrinolytic, kinin and complement cascades"
22.
23.
What does the Hageman (FXII) factor do?
Activates thrombin to propagate thrombi
24.
What does the fibrinolytic pathway do?
"Generates plasmin that degrades fibrin, ECM proteins and activates MMPs for remodelling"
25.
What does the kinin pathway do?
"FXII activates kallikrein protease > release of bradykinin > vasodilation, permeability, neutrophil chemotaxis"
26.
Describe the complement pathway?
"Proteases, antigen - antibody complexes, bacterial products >
27.
C3 -> C3a
(mast cell degranulation, permeability, chemotaxis) ,C3b (opsonistation)
28.
C3b + C5 -> C5a
(mast cell degranulation, permeability, chemotaxis), C5b (membrane attack complex)"