Inflammation Flashcards
Which two stimuli trigger inflammation?
- inflammation is triggered by infection and/or necrosis
- the inflammation attempts to clear the pathogen or the debris
- acute inflammation will always follow necrosis before healing takes place
What are the five pillars of inflammation? In addition, what is acute inflammation characterized by? Chronic inflammation?
- 5 pillars: rubor (redness), dolor (pain), calor (heat), tumor (swelling), and loss of function
- acute inflammation is characterized by edema and the presence of neutrophils as the primary immune cell
- chronic inflammation is characterized by lymphocytes and plasma cells in the inflamed tissue
What causes each of the five pillars of inflammation?
- (5 pillars are redness, pain, heat, swelling, and loss of function)
- vasodilation yields redness and heat; it’s caused by histamine, bradykinin, and PGs
- increased vascular permeability yields swelling; the edema is caused by vascular endothelial activation, histamine, and tissue damage
- sensitization of nociceptors yields pain; PGE2 and bradykinin cause this sensitization
- loss of function occurs as a result of the other processes
Quickly compare acute and chronic inflammation.
- acute: rapid onset (seconds to minutes); lasts minutes to days; mediated by neutrophils, eosinophils, antibodies, and complement; can yield complete resolution, abscess formation, or progression into chronic inflammation
- chronic: mediated by mononuclear cells (lymphocytes) and fibroblasts; a state of persistent destruction and repair; can yield granulomas, amyloidosis, and scarring
When do neutrophils arrive in acute inflammation? Macrophages?
- neutrophils: within the first 12 - 24 hours of infection
- macrophages: 24 - 48 hours after neutrophils
What are the four major mediators of acute inflammation? What does each do?
- TLRs (toll-like receptors): a PRR (pattern recognition receptor) that recognizes PAMPs (pathogen associated molecular proteins) and up regulates NF-kB
- arachidonic acid: released by phospholipase A2 and produces prostaglandins via COX and leukotrienes via 5-LPO
- mast cells: activated by tissue trauma, C3a and C5a (these are involved in anaphylaxis), and by IgE cross-linking to release histamine (causes vasodilation and increased vascular permeability)
- complement
What is NF-kB?
- this is a major switch for innate immunity to start acting
- it is upregulated by activated PRRs (pattern recognition receptors) such as TLRs
What are COX and 5-LPO?
- these are both enzymes that act on arachidonic acid once it is released by phospholipase A2; the products of both are very potent inflammatory mediators
- COX: cyclooxyrgenase; produces prostaglandins
- 5-LPO: 5-lipooxygenase: produces leukotrienes (and lipoxes)
What are the four major chemoattractants for neutrophils?
- LTB4 (a leukotriene), C5a, IL-8, and bacterial products
Increased permeability occurs at the ________, while vasodilation occurs at the _________. What is the purpose of vasodilation?
- permeability at the post-capillary venules
- vasodilation at the arterioles
- vasodilation results in the slowing of blood flow to the area, allowing neutrophils to “fall out” of the blood stream, triggering their extravasation into the tissue
What are the six steps of neutrophil extravasation? What occurs during each step:
- 1) margination: neutrophil “falls out” of the central lamina blood flow as a result of vasodilation and comes into contact with the endothelium
- 2) rolling: neutrophil’s glycoproteins loosely bind to the endothelial cells’ P-selectins and E-selectins
- 3) adhesion: neutrophil’s integrin firmly binds to the endothelial cell’s intercellular adhesion molecules (ICAMs), stopping the rolling
- 4) transmigration (AKA diapedesis): neutrophil crosses the endothelial membrane (occurs at the post-capillary venule)
- 5) chemotaxis: neutrophil moves to the infected/necrotix area via LTB4, C5a, IL-8, and bacterial products
- (phagocytosis now occurs)
What specific part of the neutrophil’s glycoproteins does the endothelial cell’s P- and E- selectins interact with?
- the Sialyl-Lewis X glycoproteins
What activates the vascular endothelium to prepare for neutrophil extravasation?
- TNF-alpha and IL-1 (released by macrophages) cause endothelial expression of P-selectin and E-selectin; they also increase endothelial expression of ICAMs
- (P-selectin is also unregulated by histamine)
- (the neutrophil’s integrin that binds to the ICAMs is unregulated by LTB4 and C5a; it’s glycoproteins that bind to the selectins is already present)
Which factors can help enhance phagocytosis?
- enhanced mainly by by IgG and C3b (this process is referred to as opsonization)
What are the two mechanisms for destroying phagocytosed material? Which cells mainly use each type?
- O2-dependent (more efficient) and O2-independent
- O2-dependent: involves the generation of oxygen free radicals within the phagolysosome to destroy the phagocytksed material; AKA “oxidative burst”
- O2-independent: phagocytosed material is degraded using enzymes from secondary granules that fuse with the phagolysosome
- neutrophils mainly use O2-dependent
- macrophages mainly use O2-independent
