Acute Inflammation Flashcards
Define inflammation. What are the components?
def: reaction of vascularized tissue to neutralize and remove injurious/infected tissue
components:
- pathogen/injury
- host cells
- complement and coagulation
- chemokines and cytokines
What are the characteristics of acute inflammation?
- short clinical duration
- immediate reaction
- accumulation of fluid, plasma proteins, and leukocytes (PMNs)
- sudden onset
What are the characteristics of chronic inflammation?
- long clinical duration
- accumulation of lymphocytes and macrophages
- proliferation of blood vessels
- formation of connective tissue at site
- slow onset
List the factors that determine intensity of inflammation.
- duration of stimulus
- type of injury
- genetics of host
- local factors (blood supply)
- medical interventions (drug interactions)
What are clinical signs of acute inflammation?
- rubor (redness)
- calor (heat)
- tumor (swelling)
- dolor (pain
systemic: fever, leukocytosis, malaise, chills
What are the overall vascular changes that occur during acute inflammation? What are the localized and systemic symptoms of these events?
- vasodilation: nitric oxide => increased flow and permeability => erythema, warmth
- leakage of fluid, plasma proteins, complement proteins, and innate immune molecules => edema
- leukocyte (neutrophil) emigration and accumulation in tissue (recruited by cytokines)
localized symptoms = swelling and warmth
systemic symptoms = increase in CO, decrease in TPR
Recall formation of an inflammasome.
- DAMPs/PAMPs activate TLRs on macrophages and monocytes
- activation of CASPASE-1
- activation of IL-1, -6, -8, and TNF-a
- formation of an inflammasome
What are the steps to leukocyte movement?
- marginalization
- rolling adhesion
- stable adhesion
- diapedesis
- transmigration
What is required for leukocyte adhesion?
- cytokines upregulate endothelial marginalization factors
2. upregulation of adhesion proteins on endothelial barrier via inflammatory cytokines
Define pseudopods.
- extensions of neutrophils and other leukocytes through the endothelial barrier before the entire cell transmigrates
Define diapedesis.
movement of neutrophils through the membrane via pseudopods
Define chemotaxis.
unidirectional movement of leukocytes along a chemical gradient composed of:
- bacterial peptides
- complement components (esp. C5a)
- arachnidonic metabolites
- inflammatory tetrad (IL-1, -6, -8, TNF-a)
gradient components trigger PMN changes in cytoskeleton makeup to allow it to move along the gradient
Describe the steps of leukocyte phagocytosis.
- Recognition and Attachment - opsonins on the surface of the injured cell/infection will bind to complementary surface proteins on macrophages/lymphocytes
- Engulfment into a phagosome via pseudopod extension around the microbe; requires actin, myosin, energy, and intracellular calcium
- Granulation within the phagolysosome via toxic enzymes
List enzymes/methods used for degradation and killing by neutrophil degranulation.
- Myeloperoxidase (MPO) in conjunction with halides (ex: HOCl)
- lysosomal enzymes
- ROS (NADPH oxidase converts oxygen to a superoxide => H2O2 => free radical)
- NETS (neutrophil extracellular traps): neutrophils release granules and chromatin to trap bacteria and fungi
Define monocytes vs macrophages.
- monocytes are circulating leukocytes with MHCII antigen presenting capabilities
- tissue macrophages are monocytes that have exited the blood and entered the tissue. They take on regional phenotypic modifications to adjust to the area.
Describe the mechanism by which acute inflammation is controlled.
- stimulus is destroyed/neutralized => decreased PAMP/DAMP
- decreased TLR stimulation => decreased inflammatory mediator production (IL-1, -6, -8, TNF-a) by activated macrophages
- neutrophilic granule release prevents more neutrophils from entering the site; instead they recruit monocytes
- decreased TLR stimulation => conversion of M1 macrophages to M2 => production of IL-10 and TGF-b => antiinflammatory milieu sets the stage for cleanup and repair
What are the outcomes of acute inflammation?
- resolution and repair
- chronic inflammation
List the 4 classifications of acute inflammation in order of severity.
- serous
- fibrinous
- supperative/abscess
- ulcerative (special category)
Characterize serous acute inflammation.
- protein poor transudate from blood vessels into peripleural space (ex: pericardial, peritoneal, between epidermis and dermis (blister)
Characterize fibrinous acute inflammation.
- fluid with larger molecules (mostly fibrinogen) from blood vessels into extracellular space
- fibrinogen converts to fibrin => scaffold for scar formation
Characterize abscess/supperative acute inflammation.
- collection of protein-rich fluid, containing inflammatory cells and debris ==> pus
- if walled off by fibroblasts => abscess
Define abscess.
collection of inflammatory cells, debris (pus) surrounded by fibroblasts
Characterize ulcerative acute inflammation.
- underlying inflammation causes excavation of skin or mucos to form indentations (ulcers) in the mucosal linings or surface
What kind of tissue can undergo acute inflammation?
VASCULAR
Define PAMPs vs DAMPs.
PAMPs = Pathogen-Associated Molecular Patterns
- microbes
- viruses
DAMPs = Damage-Associated Molecular Patterns
- ROS
How does smoking affect acute inflammation control?
- turns off PMN prevention signal
- neutrophil recruitment and release continue
- chronic inflammation b/c monocytes aren’t recruited
Define proliferative pool vs maturation pool of PMNs.
Once PAMPs/DAMPs are activated, activated macrophages stimulate PMNs in both pools.
- proliferative = bone marrow activation of PMNs by cytokines and growth factors
- maturation = circulating monocytes
What is the characteristic immune cell of acute inflammation?
- neutrophils
- most numerous innate immune cell in circulation
Define bandemia.
- stimulation of proliferative pool causes release of not-fully-matured PMNs into circulation
- circulating PMNs undergo a “left shift” to a less mature level overall during inflammation
