Flashcards in Evolution of Inflammatory Diseases Deck (57)
Give 2 examples of potentially lethal inflammatory responses?
anaphylaxis and septic shock
What is the advantage and disadvantge of increased mucus production by goblet cells?
enhances epithelial barrier defenses but leads to mucus plug formation and reduced gas exchange at respiratory epithelia
Why might you expect taht the cost-benefit trade-off of the inflammatory response in modern populations is not optimised to the current environmnet?
there have been massive changes in environmental factors in the past century- poplation density; diet; hygiene; antibiotics; vaccines
What are the 2 main plasma antioxidants?
urate and bilirubin
What is the function of lipoxins?
inhibit the recruitment of neutrophils and promote the recruitment of monocytes
what is hte function of monocytes in the resolution and repair phase of inflammation?
remove dead cells and initiate tissue remodelling
What is the function of resolvins and protectins?
transform growth factor b and growth factors produced by macrophages; intiation of tissue repair
What happens if macroaphges and T cells cannot resolve an an infection?
chronic inflammatory state ensues with granuloma formation and teritiary lymphoid tissue formation
What is the function of granulomas?
an attempt to wall off intruders by layers of macropahges
What cell senses the proteolytic activity of proteases produced by helminths?
Why might allergens induce inflammation?
mimic the virulence of parasites (e.g act as a protease) or irritate the mucosal epithelia
What are foreign bodies?
indigestible particles that are either too largeto be phagocytosed or cause phagosomal memrbane daamge in macropahges
What is frustrated phagocytosis?
phagocytic cup is formed but cannot close to form a phagosome (e.g large size of shapre)
What happens if a foreign body is too large for a phagocytic cup to be ofrmed?
macropahge forms a granuloma around the body
What are the actions of ATP released by necrotic cells?
binds to purinoceptors at the maceroaphge surface resulting in K efflux which activates the NLPR3 inflammasome; activates nociceptors- reports tissue injury to the nervous system
What is the action of HMGB1 released by necrotic cells?
binds to RAGE and TLRs to induce an inflammatory response
What is the non-canonical patwhay of release of intracellular proteins
not via the ER and golgi; mediated by activated caspase 1 i.e the inflammasomes (requires ATP)
When might the non-canonical secretory pathway be invovled?
HMGB1 is released from macropahges when TLR4 is stimulated with LPS in the absence of necrotic death
What hapens when there is disurption of the basement membrane?
unschedulaed epithelail-mesenchymal interactions which indicate the presence of tissue damage
What are the 2 class of microbial induce?
PAMPs and virulence factors
Give examples of non-microbial inducers?
allergens; irritants; foreign bodies; toxic compounds
How does the growth factor heregulin act as an endogenous inducer in the airway epithelium?
hergulin is apically expressed whereas its receptors are basolaterally expressed, when there is epithelial injury, hergulin can bind to its receptors and initiate a tissue-repair response
What happens when urate crytals reach a certain size?
detected by macroaphges and treated as foreign bodies, phagocytosis triggers activation of NLRP3 and IL production
What are AGEs?
products of non-enzymatic glycation of long-lived proteins eg collagen
When do AGEs accumulate?
hyperglycaemic or pro-oxidative conditions- diabetes, ageing
What receptor recognises AGE?
What are the 7 groups of inflammatory mediator?
vasoactive amines; vasoactive peptides; fragments of copmlement components ; lipid mediators; cytokines; chemokines and proteolytic enymes
give examples of vasoactive amines?
histamine and serotonin
Give an example of a vasoactive peptide that is stored in its active form in secretory vesicles?