Inflammation and the regulation of the IR Flashcards
General features of inflammation
beneficial host response- defends against foreign invaders and gets rid of necrotic tissue
can itself cause damage
main components; vascular response and cellular response
activated by mediators: cellular and plasma proteins
Acute inflammation possible sequelae: resolution; repair (scarring); abscess formation (walling off), chronic inflammation
Causes of inflammation
microbial infections: bacteria, viruses, fungi
hypersensitivity: type I- IV
physical agents: burns, UV light, radiation
Chemicals: acids, alkalis, oxidizing agents
Tissue necrosis: ischemia- loss of blood supply (kidney prone to ischemic damage due to lack of collateral blood supply)
Inflammatory mediators
orchestrate IR
widely distributed through the body in the INACTIVE form
at site on inflammation–> released/synthesized/activated locally; rapidly inactivated upon resolution to minimize inflammation
Cell-derived mediators
any cell involved in inflammation can produce mediators, i.e tissue macrophages, endothelial cells and recruited WBCS
vasoactive amines: histamine, serotonin–> vasodilation and increased vascular permeability
arachidonic acid metabolites (fever/pain): prostaglandins, leukotrienes (inhibit/dampen inflammaiton)–> vascular reaction, leukocyte chemotaxis
Cytokines: lots of cells produce CKs; usually act at short range
TNF, IL-1, and chemokines
ROS: microbe killing, tissue injury
NO: vasodilation, microbe killing
lysosomal enzymes: microbial killing, tissue injury (if you get lysosomal enzymes expresed where they shouldn’t be)
Plasma-protein derived mediators
from liver: circulating proteins of 3 interrelating systems: complement; coagulation (fibrinolysis) and kinin systems
complement proteins: antibody or microbe activation– leukocyte chemotaxis, opsonisation and phagocytosis of microbes; cell killing
coagulation proteins: activated factor XII triggers: clotting, kinin and complement cascades; actiates fibrinolytic system
kinins: proteolytic cleavage of precursors–> mediate vascular reaction, pain.
NB: liver function will affect–> get decrease in liver function, get decrease in plasma proteins.
Cellular events
WBC activation, enhanced function
particle phagocytosis: early step in elimination of harmful substances
production of substances which destory phagocytosed microbes, remove dead tissues (e.g. lysosomal enzymes, ROS, RNS)
production of mediators which amplify inlammatory response (e.g. arachidonic acid metaboites and cytokines)
Phagocytosis: positive effects (ideal)
- recognition and attachment: microbes bind to phagocyte receptors
- engulfment: phagocyte membrane zips up around microbe
- microbe ingested in phagosome
- fusion of phagosome and lysosome
- phaoglysosome kills microbe by ROS and NO
- degradation of microbes by lysosomal enzymes in phagolysosome
NB: if lysosomal enzymes leak–> get problems
Luekocyte-induced tissue injury
Enhanced function for GOOD but activated cells don’t distinguish between offender and host. this leads to a release of lysosomal enzymes into the extracellular spaces which leads to WBC-induced tissue injury
Backfiring of phagocytosis
release of lysosomal granules into the extracellular space
regurgitation during feed wherein the phagolysosome briefly stays open
frustrated phagocytosis where substances are difficult to chew on different surfaces- high activation results in a lot of substances being released
phagolysosome membrane damage- sharp substances e.g. urate crystals (gout)
Clinical examples of WBC-induced injury
Asthma- eosinophils and IgE
Glomerulonephritis- antibodies and complement; n’phils and monocytes
septic shock: cytokines
arthritis: lymphocytes, macrophages and antibodies
pulmonary fibrosis: macrophages and fibroblasts
Special inflammatory lesions
Abscess: walled-off acute inflammation in solid organs- isolated from the rest of the body; have to treat
Cellulitis: pus extends through fascial planes
Epithelial surfaes: diphtheritic membrane (necrotic epithelium sloughs off as it degenerates); ulceration
Abscess development
develops when acute inflammatory response fails to eliminate the cause; enzymes and inflammatory mediators liquefy affected tissue and neutrophils
- abscessation is a defense to prevent uncontrolled multiplication of bacteria. if bacteria proliferate unchecked–> septicemia
- neutrophils are 1st line of defense. derived from blood and engulf bacteria. release enzymes which can destory bacteria and tissues.
- abscess center (pus): mixture of debris, degenerative neutrophils and bacteria. At the edge, there are scavenging cells (macrophages), and other cells (plasma cells and lymphocytes) producing antibody. Whole structure is contained by a fibrous capsule.
Bacteria enters–> neutrophil infiltration from BVs–>abscess formation (fibrotic tissue capsule, necrotic center)–> fibrous tissue scar
Cellulitis
pus tracking through fascial planes; might see oedema; very painful
diphtheritic membrane
necrotic epithelium + neutrophils + microbes
Macrophages
free and fixed macrophages
e.g. fixed: kupffer cells in liver, alveolar macs
histiocytes (fixed macrophages of skin)- Langerhan’s cells
process and present antigen to the immune system- part of innate immune system
major source of cytokines
In granulomatous inflammation, 90% of cells are macrophages
Langhan’s giant cells: multiple macrophages with a horse shoe shape
Epithelioid macrophage: activated macrophage
Foreign body giant cell: more random than Langhan’s cells (not in horseshoe shape)
