Flashcards in Inflammation Deck (75):
What is inflammation?
a host defense response to infection and tissue damage intended to eliminate the offending agents
What are 4 main causes of inflammation?
infections (bacterial, viral, fungal, parasitic), tissue necrosis (ischemia, trauma, injury), foreign bodies (exogenous or endogenous), immune reactions (hypersensitivity)
What is the onset and duration of acute inflammation?
develops within minutes to hours, short duration
What are local features of acute inflammation?
redness, heat, swelling/edema
What cells are involved in acute inflammation?
neutrophils and other phagocytes (innate immunity cells)
What are the 3 possible outcomes of acute inflammation?
resolution, resolution w fibrosis, or progression to chronic inflammation
What is the onset and duration of chronic inflammation?
develops over days to months, long duration
What cells are involved with chronic inflammation?
lymphocytes, plasma cells, monocytes, macrophages, fibroblasts (adaptive immunity cells)
What is the outcome of chronic inflammation?
progressive and sometimes severe tissue damage with fibrosis
What effect does fibrosis have on tissue?
What blood vessel changes occur in acute inflammation?
increased flow due to vasodilation, increased permeability
What is the difference between endothelial cell retraction vs. injury?
retraction is induced by mediators and is rapid, short lived, and reversible
injury is caused by burns or toxins and can be rapid but long lived (resulting in edema)
What two forces balance vessel pressure?
colloid osmotic pressure (water in) and hydrostatic pressure (water out)
What are the two types of fluid leakage?
exudate and transudate
Describe an exudate vessel.
fluid and protein leakage, vasodilation and increased permeability, characteristic feature of inflammation
Describe a transudate vessel.
fluid but no protein leakage, not a feature of inflammation, usually associated with CHF and edema
What is margination?
leukocyte movement to peripheral region of blood flow
What receptors mediate margination?
What receptors mediate leukocyte adhesion to endothelial cells?
What is diapedesis?
leukocytes traversing the endothelium
Which process follows diapedesis?
What is chemotaxis?
migration along chemical gradient due to chemoattractants
What are the two classes of chemoattractants?
exogenous (bacterial products) and endogenous (chemical mediators)
What is the primary component of cellular infiltrate 6-24 hours after inflammation begins?
What is the primary component of cellular infiltrate 24-48 hours after inflammation begins?
What are the steps in the process of phagocytosis?
1. recognition and attachment
2. engulfment of microbe and creation of phagosome
3. fusion of phagosome with lysosome to form phagolysosome
4. killing and degradation
What are 3 pathways for microbial killing?
ROS, NO, lysosomal enzymes/proteins
What is the killing agent formed in the ROS pathway?
What is the killing agent formed in the NO pathway?
What are the 2 steps in the ROS pathway?
NADPH oxidase generates superoxide anion
superoxide anion generated H2O2 which works with myeloperoxidase and Cl to generate hypochlorite
What are the 2 steps in the NO pathway?
inducible nitric oxide synthase (iNOS) generates NO
works with superoxide anion to generate peroxynitrate ONOO-
What 4 lysosomal enzymes are responsible for microbial killing?
lysozyme, collagenase, elastase, acid hydrolase
What are 3 protective mechanisms against unwanted tissue damage by killing pathways?
location, antioxidants, antiproteases
What is the function of an antioxidant?
get rid of excess ROS in body
What to antiproteases act against?
elastases and collagenases
What are 4 primary antioxidants?
superoxide dismutase, catalase, glutathione peroxidase, ceruplasmin/transferrin
What are the 2 primary antiproteases?
alpha-1-antitrypsin and alpha-2-macroglobulin
What are the 4 classes of mediators of acute inflammation?
arachidonic acid metabolites
What are the vasoactive amines?
histamine and serotonin
What are AA metabolites derived from?
cell membrane phospholipids
Which two enzymes create different AA metabolite pathways?
cyclooxygenase or lipoxygenase
What inhibits the formation of AA?
What inhibits the function of cyclooxygenase?
COX-1 and COX-2 inhibitors, aspirin, indomethacin
Which 4 AA metabolites are derived from the cyclooxygenase pathway?
prostacyclin (PGI2), thromboxane A2 (TXA2), PGD2, and PGE2
Which 7 AA metabolites are derived from the lipoxygenase pathway?
HETE, Leukotriene (LTB4, C4, D4, E4), Lipoxin (LXA4, B4)
causes vasodilation, inhibits platelet aggregation
causes vasoconstriction, promotes platelet aggregation
causes vasodilation, increased vascular permeability
LTC4, D4, E4
bronchospasm, increased vascular permeability
inhibition of inflammation
What are the primary cytokines in acute inflammation?
TNF, IL-1, IL-6, chemokines, IL-17
How do cytokines affect the endothelium?
increase permeability and expression of adhesion molecules
How do cytokines affect the brain?
How do cytokines affect the liver?
acute phase protein production increase (IL-1, IL-6)
How do cytokines affect bone marrow?
Stimulate leukocyte production (TNF, IL-1, IL-6)
How does TNF affect the heart?
How does TNF affect thrombosis?
How do cytokines affect muscles?
insulin resistance (TNF, IL-1)
What are chemokines?
small chemoattractant proteins
Where do chemokines bind?
bind to 7 transmembrane G-protein coupled receptors
Which mediator is at the central part of the complement system?
What cleaves C3 and into what parts?
C3 convertase, C3a and C3b
What is a MAC?
membrane attack complex
What makes up a MAC?
Which complement system mediators are involved in recruitment and activation of leukocytes?
C5a and C3a
Which complement system mediator is involved in phagocytosis?
What is pus?
collection of dead cells and cellular debris (both regular tissue and microbes)
What are 3 causes of chronic inflammation?
persistent infections, hypersensitivity diseases, prolong exposure to toxins
What are 3 morphologic feature of chronic inflammation?
mononuclear cell infiltration, tissue destruction, attempts at healing
What are cellular features of granulomatous inflammation?
macrophages with abundant cytoplasm, giant cells, T lymphocytes, and variable necrosis
What are some causes of granulomatous inflammation?
foreign material, mycobacterial or fungal infection, and certain immune reactions
How do acute phase protein levels change during inflammation?
How do white blood cell levels change during inflammation?