acute and chronic inflammation part 1 Flashcards
A broad understanding of inflammation in terms of historical discovery and identification, functions and context within the body, types of inflammation, contributing components. The mechanisms of acute inflammation.
what is inflammation
is a protective response to tissue insult or injury aimed at eliminating the cause of injury, remove damaged celled and initiate repair
what are the 5 carinal signs of inflammation
calor/warmth rubor/ redness/ erythema tumor/ swelling/ oedema dolor/ pain functino laesa/ lack of function
what did john hunter propose
that inflammation wasn’t a disease but a response to tissue injury
when did john hunter propose this idea
late 18th century
who introduced the idea of functino laesa
ruodolf virchow- the father of pathology
which cells are involved in an inflammatory response
Circulating plasma proteins and cells of the immune system.
Vasculature and it’s endothelium
Liver production of proteins of complement, clotting and acute phase.
what are souces of mediators
nitric acid
histamines
cytokines
what do PMN leukocytes do
elimination of microbes and dead tissue
what do extra cellular proteins matrix do
repair
when is an inflammatory reaction triggered
induced by chemical mediators that are produced by host cells in response to injurious stimuli
what are the steps for an inflammatory response
RECOGNITION- of injurious RECUIRTMENT- of leukocyte REMOVAL- of the agent causing the injury REGULATION- of the response RESOLUTION- of the response and repair
examples of the injurious stimuli which can trigger inflammatory reactions
infectious agents- bacteria, yeast, virus
foreign bodies
immune reactions eg immune complex like antigen- antibody complex
physical
irration
thermal injury
what do we call the immune complex if it is self
auto immune complex
what can happen if the noxious stimulus cannot be removed and or the acute inflammatory response is not resolved
can lead to state of chronic inflammation
when can inflammation cause damage
Very strong inflammatory reaction (e.g. severe infection).
Prolonged reaction (agent resists eradication)
Response is inappropriate (e.g.self or harmless environmental antigen)
what does thermal injury lead to sometimes
tissue necrosis
what is the onset of acute inflammation
fast min hours
what is the duration of acute inflammation
short few mins- few days
what are the infiltrating cells in acute inflammation
PMNS and macrophage
what type of injury is caused in acute
self limiting
what are the local systemic signs of acute inflmmation
prominent
what is the onset of chronic inflammation
slow, days
what is the duration of chronic inflammation
variable
possible months and years
what are the infiltrating cells in chronic inflammation
macrophage and lymphocyte due to the fact adaptive immune system to contribute
what type of injury is caused in chronic
severe gets progressively worse
what might differ between acute and chronic inflammation macrophages
might be activated differently and might be activated differently
what is the local and systemic signs of chronic
less prominent can be subtle
what are the two major groups of activities in acute inflammation
vascular changes
cellular events
what does acute inflammation do
delivers leukocytes and plasma proteins to the injury site
leukocytes clean infection and dead cells
what is included in vascular changes
vasodilation
vascular permeability
endothelial cell activity
what is included in cellular events
leukocyte recruitment
activation og leukocyte infiltrating tissue
describe recognition of injurious stimulus
Phagocytes, Dentritic Cs and epithelial cells express PRR (Pattern Recognition Receptors) to recognise and bind to distinct molecular patterns not seen in healthy vertebrate cells.
describe the pathway of initiation of inflammation with macrophages
engulf invading pathogens which triggers them to release pro inflammatory cytokines
give examples of pro inflammatory cytokines
TNF-α, IL-1β, IL-6) and chemokine (CXCL8 aka IL-8
what is a cytokine
secreted in response to a stimulus, affect the behaviour of cells (autocrine, paracrine, endocrine)
what is a chemokine
a chemoattractant protein that stimulates the migration of cells (phagocytes and lymphocytes).
describe mast cells
located close to body surfaces
release of preformed histamine from granules
anti-parasitic activity and key player in allergic response
express receptor for IgE coated with IgE they are triggered to degranulate when this IgE binds to its ligand
describe epithelial cells
cells that line our mucosal surfaces
express PRR
maintain homeostasis with commensal bacteria but can respond to pathogens initiating inflammatory responses
what do epithelial cells secrete
CXCL-8, TNF-α , IL-1β, IL-18 and antimicrobial peptides.
what are the different types of cytokine
autocrine
paracrine
endocrine
what is an autocrine cytokine
the cytokine acts back on the one that secretes it
what is paracrine cytokine
acts on a different cell that one that secreted
what is a endocrine cytocine
has to enter the blood stream and travel to a different site
what type of structures are toll like receptors
heterodimeric
homodimeric
where are TLR found
span the plasma membrane and allow extracellular recognition
or inside the cell and allow for endosomal recognition
what does TLR3 detect
double stranded RNA- can be involved in viral replication
what does TLR7 detect
single stranded RNA- not found usually in the endosomnal space
what does TLR 9 detect
cpG DNA- recognises unmethlyated CpG DNA
which TLR are found in the endosomal space
TLR3, TLR7, TLR9
which TLR are found on the plasma membrane
TLR2, TLR6, TLR, 1,TLR5, TLR4,
which receptors come together to detect diacyl lipopeptides
TLR2, TLR6
which TLR come together tot detect triacyl lipopeptides
tlr2, tlr1
what do TLR2, TLR6 complex detect
diacyl lipopeptides
what do TLR2, TLR1 complex detect
triacyl lipopeptides
what does TLR5 detect
flagellin
what does TLR4 detect
LPS
what type of receptors provide cytosolic recognition
RIG-I and NOD like receptors
what does RIG-I bind to
viral RNA- unmodified 5 prime
what does NLR bind to
bacterial lipids eg peptidoglycan
how does RIG-I differentiate between viral RNA and self RNA
unmodified 5 prime triphosphate on the viral RNA different to messenger RNA
What does the NLRP3 inflammasome detect
dead cell components( extracellular ATP uric acid)
crystals- uric and gout and some pathogenic bacterial components
what is the pathway of the NLRP3
forms the NLRP3 inflammasome in the cytoplasm —-> joins on with caspase 1 present in proform ——> activates caspase 1 ——-> zymogen cascade—-> cleaves and activates IL1 beta
what are the three stages of recruitment of leukocytes
vasodilation
vascular permeability
endothelial cell activation
what does vasodilation include
widening of blood vessel calibre increases blood flow
leads to erythema and heat
what does vascular permeability include
permits the extravasation of plasma fluid and proteins to exit and enter the tissues - oedema
what does endothelial cell activation include
changes to luminal vessel surfaces and reduced blood flow and reduced blood flow speed to allow leukocytes to pass through the endothelial layer, gaming entry to tissues
what does vasodilation lead to clinically
erythema and heat
what does vascular permeability lead to clinically
oedema
what does endothelial cell contraction can be induced by
cytokines IL-1 (interleukin 1) and TNF (tumour necrosis factor)
Histamine and kinins
what does damage to the endothelium lead to
necrosis of cells due to a burn, UV, toxins, leukocytes induced damage
what is margination aided by
vessel dilation and reduced blood flow
what is margination
WBC found at the periphery of the vessel whereas RBC are located in the middle of the vessel
what is the rolling stage
pro inflammatory cytokines/ histamine will activate endothelial cells—-> express adhesion molecules(selectins) on luminal surfaces
what is stable adhesion
interactions between integrins (leukocytes) and cell adhesion molecules (endothelium). WBC stops rolling and adheres to the vessel wall
what are the stages of recruitment of leukocytes
margination rolling stable adhesion transmigration chemotaxis
what is transmigration/ (diapedesis)
leukocytes squeeze through intercellular endothelial junctions
what is chemotaxis
movement along a chemical gradient (cytokines/ chemokines, C5a, Arachadonic acid metabolites, bacterial products)
what do plasma proteins do
mediators of inflammation and clotting factors
