Inflammation and repair Flashcards
what is the purpose of inflammation
protective response intended to eliminate cause of cell injury
Inflammation is part of what type of immunity
innate immunity
characteristics of acute inflammation
sudden and short term
characteristics of chronic immunity
gradual and prolonged
inflammation is induced by ______ produced by _____
chemical mediators; injured host cells
when a tissue is injured, different cells secrete _____ that _____ and ____ inflammatory response
chemokines; induce and regulate
what are the main components of inflammation
- vascular changes (vasodilation and increased vascular permeability)
- cellular events (cellular recruitment and activation)
what are the Five Rs of inflammatory response
- recognition of injurious agent
- recruitment of WBCs
- removal of agent
- regulation of the response
- repair (resolution)
what are the cardinal signs of inflammation
Heat, redness, swelling, pain, and loss of function
what causes redness
dilation of arterioles and increase blood flow
what causes heat
increased chemical activity and increase blood flow to surface
what causes swelling
accumulation of blood and damaged tissue cells
what causes pain
direct injury of nerve fibers, pressure
what causes loss of function
increased pain/swelling
the primary cause of redness, heat, swelling/edema is
histamine which increases fluid into tissue
the primary cause of pain is
bradykinin and PGE2
major local manifestations of acute inflammation are
- vascular dilation and increased blood flow (erythema and heat)
- extravasation of plasma fluid and proteins (edema)
- leukocyte emigration and accumulation
how do cell recognize presence of potentially harmful agents
immune cells have pattern recognition receptors designed to sense presence of pathogens (toll like receptors and inflammasome)
what are toll like receptors
microbial sensors on plasma membrane or endosomes that recognize extraceullar and ingested microbes
what are the functions of toll like receptors
activates transcriptions factors that stimulate production of secreted and membrane proteins that promote lymphocyte activation
what are inflammasome
multiprotein cytoplasmic complex that recognize products of dead cells
what is the function of inflammasome
activates caspase-1 resulting in WBC recruitment
interstitial fluid accumulation is caused by
increased hydrostatic pressure
protein rich fluid accumulation is typical in
inflammation
what are the mechanisms involved in increased vascular permeability
- endothelial cell contraction leading to gaps in post capillary venules
- endothelial injury
- increased transcytosis of proteins
- leaking from new blood vessels
what role do lymphatic response have in inflammation
increase lymph flow and help remove excess water, WBC, debris from extravascular space
lymphangitis is
inflamed lymphatics
lymphadenitis is
inflamed lymph nodes
leukocyte work to
ingest agents, kill bacteria, and eliminate necrotic tissue
the steps for leukocyte recruitment are
- margination and rolling
- adhesion
- transmigration
- migration
define what occurs at margination
when leukocytes accumulate at periphery of vessels
what occurs during rolling
cytokines activate endothelial cells, express adhesion molecules to which WBCs attach loosely
what occurs during adhesion
mediated by integrins expressed on WBC interacting with their ligand on endothelial cells
in diapedesis,
WBCs migrate through vessel wall
WBC move towards site of injury by what
chemotaxis
how are leukocytes activated
by microbes products of necrotic cells and chemical mediators
leukocyte activation promotes:
- phagocytosis
- release substances to destroy microbes
- produce chemical mediators
what are the phagocytosis steps
- recognition and attachment
- engulfment and formation of phagocytic vacuole
- killing and degradation of ingested material
what causes injury to normal cells and tissues
- defense against difficult infections
- autoimmune reactions
- XS host reaction
what are the possible outcomes to acute inflammation
- resolution
- chronic inflammation
- scarring (fibrosis)
characteristics of serous inflammation
skin blister from burn or viral infection
characteristics of fibrinous inflammation
due to see injuries that result in exudate of fibrinogen leading to fibrin
characteristics of ulcerative inflammation
ulcer on surface of organ
characteristics of supurative (purulent) inflammation
presence of large amounts of purulent exudate (pus) and edema fluid
cell derived mediators
- vasoactive amines
- arachidonic acid metabolites
- platelet activating factor
- cytokines
- reactive oxygen species
- nitric oxide
- lysosomal enzymes of WBC
- neuropeptides
plasma protein derived mediators include
- complement proteins
- coagulation protein
- kinins
complement proteins are responsible for
leukocyte chemotaxis, opsonization, and phagocytosis of microbes and cell kiling
coagulation proteins are activated by
factor XII that will active the fibrinolytic system (triggers clotting, kinin and complement cascade)
kinins are produced by
proteolytic; mediates vascular reaction and pain
chronic inflammation is characterized by
inflation with mononuclear cells, tissue destruction induced by byproduct of inflammatory cells, and repair involving anigogenesis and fibrosis
what cells is most dominant in chronic inflammation
macrophages
how are macrophages activated
- by microbial products
- induced by cytokines
role of lymphocytes in chronic inflammation
migrate to injury sites
B cells develop to what in tissues
plasma cells and CD4+ lymphocytes
eosinophils are found in
parasitics inflammatory response mediated by IgE (allergies)
Mast cells are …
sentinel cells in connective tissue. produce cytokines (TNF, chemokines)
granulomatous inflammation known as
- clusters of T cell activated macrophages to engulf foreign bodies
what are the most important mediators of acute phase reaction
TNF, IL-1, and IL-6
system effects of acute phase response
- fever
- plasma levels of acute phase proteins
- leukocytosis
repair occurs by
- regeneration of injured tissue (proliferation of uninjured cells)
- scar formation (if tissue not capable of regeneration)
what are the methods that macrophages are activated
- induced by microbial products, T-cell signals, and foreign substances (classical)
- induced by cytokines produced by T-cells, eosinophils and mast cells (alternative)
what cell types proliferate during tissue repair
-remnants of injured tissue
- vascular endothelial cells
- fibroblasts
body tissue can be divided into what kinds of tissues
- labile tissue
- stable tissue
- permeant tissue
describe labile tissues
continuously lost and replaced by stem cells (bone marrow hematopoietic cells, epithelial cells)
describe stable tissues
quiescent with minimal proliferative capacity (parenchyma of solid tissues, endothelial cells, smooth muscle fibers, fibroblasts)
describe permanet tissues
postnatally terminally differentiated and non proliferative (cardiac muscle)
what is extracellular matrix made up of
collagen, glycoproteins, basement membranes underlying epithelia and surrounding vessels
what function does ECM serve
- provide mechanical support to tissues (collagen and elastin)
- acts as substrate for cell growth
- regulates cell proliferation and differentiation
steps in scar formation are
- angiogenesis
- activation of fibroblasts
- remodeling
angiogenesis is
process of new blood vessels development from existing vessels
angiogenesis is critical in
- healing injury
- development of collateral circulation at sites of ischemia
- allowing tumors to growth
activation of fibroblasts and deposition of connective tissue occurs in two steps:
- migration and proliferation of fibroblasts into injury site
- deposition of ECM protein
what growth factors are involved in activation of fibroblasts
TGF-Beta, PDGF, FGF
