Acute Inflammation Flashcards
what’s an infectious inflammatory disease?
inflammation caused by an infectious disease
what’s a sterile infectious disease?
inflammation without an infectious cause
what’s the overarching aim of inflammation?
to remove damaged tissue/pathogen in order to allow repair
which immune system plays a central role in inflammatory line of defense?
Innate Immune system
What is acute inflammation?
rapid inflammatory response to infection/injury
how long does acute inflammation last?
hours-days
what are the 6 causes of acute inflammation?
microbial infections
hypersensitivity reactions- e.g. nickel allergy
chemical injury- e.g. burn
physical injury
tissue necrosis-e.g. during/after a stroke
autoimmune diseases- directed against a self-antigen
when does acute inflammation cease?
once the cause has been removed (pathogen/damaged tissue)
what is suppurative (purulent) inflammation?
macroscopic appearance of inflammation
large amounts of pus containing dying/dead neutrophils, microorganisms and oedema fluid. (may be walled off by tissue causes abscess)
what is fibrinous inflammation?
macroscopic appearance of inflammation
lots of fibrinogen which polymerises to form a thick fibrin coating
what’s pseudomembranous inflammation?
macroscopic appearance of inflammation
growth of surface layer made of disrupted mucosa, fibrin, mucus and inflammatory cells (often caused by antibiotics)
what is serous inflammation?
macroscopic appearance of inflammation
lots of protein-rich fluid exudate
what is cattarhal inflammation?
macroscopic appearance of inflammation
hypersecretion/ inflammation of mucous membrane
what’s hemorrhagic inflammation?
macroscopic appearance of inflammation
inflammation caused by severe vascular injury
what’s membranous inflammation?
macroscopic appearance of inflammation
epitheilium coated with fibrin, desquamated epithelial cells and inflammatory cells
what’s necrotising inflammation?
macroscopic appearance of inflammation
high tissue pressure (from oedema) leads to vascular occlusion and thrombosis, leading to widespread septic necrosis of affected organ
what are the vascular (on site) characteristics of inflammation? (5) (more prevalent in acute inflammation)
- heat
- soreness
- redness
- swelling
- loss of function
What are the systemic characteristics of inflammation? (tend to be more prominent in chronic inflammation)
- fever
- lethargy
- loss of appetite
- leukocytosis (increased leukocytes)
what’s the overall process of acute inflammation?
- recognition of damaged tissue/ pathogens
- release of chemical mediators
- recruitment of leukocytes and plasma proteins
- increased blood flow and permeability allow them to reach site
- they enter tissues and release chemical mediatiators (e.g. phagocytes) to eliminate pathogen/ necrotic tissue
- tissue can then repair
what are PRRs?
Pattern Recognition Receptors
What to PRRs recognise?
PAMPs and DAMPs
What are PAMPs?
Pathogen Associated Molecular Patterns
- highly conserved structures in bacteria, fungus and viruses
What are DAMPs?
Danger/ Damage associated Molecular Patterns
- released by necrotic cells
what are TLRs?
Toll Like Receptors
Where are TLRs found?
cell/ endosome membranes
what do TLRs detect?
both DAMPs and PAMPs
which PAMPs do TLRs detect?
microbial RNA/DNA, flagellin and LPS
what is LPS?
Lipopolysaccharides - a major component of gram-negative bacteria
which DAMPs do TLRs detect?
heat shock proteins, ECM components, oxidised LDL
What is Pentaxin?
A PRR
where is Pentaxin found?
extracullularly (in blood stream)
What does Pentaxin detect?
PAMPs- phosphocholine in microbial membranes
How many TLR types are there?
13
How many TLRs are there in humans?
10
Are TLRs membrane spanning?
yes
what do TLRs do after detecting PAMPs/DAMPs?
induce inflammatory genes
What does the extracellular region of TLRs contain?
leucine-rich repeats to form a ligand bidning domain (horseshoe shaped) which dimerises upon ligand binding
what do endothelial cells secrete in acute inflammation?
NO (nitric oxide)
what does NO do?
vasodilation
what does vasodilation do?
increases delivery of plasma and blood cells to site of inflammation
which cells enter the site first in acute inflammation?
neutrophils
which immune cells are the most numerous in the blood stream?
neutrophils
which immune cells are fastest to respond to chemokine release?
neutrophils
how do neutrophils attach to endothelial cells?
using adhesion molecules
what do neutrophils generate?
reactive oxygen and nitrogen species
what’s the difference between monocytes and macrophages?
they’re monocytes when in blood stream
they’re macrophages in the tissue
what’s the main, immune property of macrophages?
they’re phagocytic
what do macrophages generate?
cytokines
reactive oxygen species
what do mast cells produce?
histamine and other enzymes involved in allergies
what does histamine do?
causes dilation and permeability of BVs
what do platelets do in an inflammatory response?
blood clotting
synthesise serotonin
what is meant by a vasoactive chemical mediator?
chemical that’s active on blood vessels
give 4 examples of vasoactive chemical mediators
histamine
serotonin
lomoms
eicosanoids
generally, what are eicosanoids?
signaling molecules
what are the 2 main examples of eicosanoids?
Prostaglandins (PGs)
Leukotrienes (LTs)
what produces prostaglandins?
mast cells, macrophages, endothelial cells
which parts of inflammation are prostaglandins involved in?
systemic and vascular reactions
what secretes leukotrienes?
leukocytes
what are leukotrienes made from?
12- lipoxygenase
what’s the difference between lipoxins and leukotrienes?
lipoxins are anti-inflammatory
leukotrienes are inflammatory
where at PGs and LTs derived from?
phospholipid bilayer
what are cytokines?
protein/polypeptide mediators synthesised and released by cells of the immune system during inflammation
they aid in the coordination of the inflammatory response
act locally by autocrine or paracrine mechanisms
what are chemokines?
a type of cytokine that control the migration of leukocytes and mediate their activity by binding to GPCRs
what are the 2 important chemokines to remember?
TNF-a and IL-1B
what are TNF-a and IL-1B?
interleukins
other than chemokines, what receptors do most cytokines act on?
kinase-linked receptors
what vascular inflammatory actions do TNF and IL-1 have? (5)
- increase leukocyte adhesion molecules
- increase pro-coagulant activity
- reduce anti-coagulant activity
- activate leukocytes
- produce other cytokines
what repair actions do TNF and IL-1 have?
- increase fibroblast proliferation
- increase collagen synthesis
what systemic inflammatory actions do TNF and IL-1 have?
- fever
- leukocytosis
- increase acute phase proteins
- reduce appetite
- increase sleep
what makes phagocytosis more effiecient?
opsonization
how are complement proteins activated?
by proteolytic cleavage when they leave blood plasma
what’s the critical step of the complement cascade?
cleavage of C3
how many pathways can cause cleavage of C3?
3
what are the 3 pathways that cause cleavage of C3?
classical
lectin
alternative
what happens in the classical pathway?
fixation of C1 to antibody combined with antigen
what happens in the lectin pathway?
triggered by binding of mannose lectin
what happens in the alternative pathway?
triggered by microbial surface particles
what’s the general process/ order of complement proteins?
C3 (activated)–> C3a –> C3b –> C5a–> C 5,6,7,8,9 (membrane attack complex)
what are reactive oxygen species involved in?
phagocytosis
what are 2 important reactive oxygen species?
super oxide
hydrogen peroxide
what is Nitric Oxide (NO)?
soluble gas produced from arginine by the action of NOS
What’s NOS?
Nitric Oxide Synthase
how many isoforms of NOS?
3
what are the 3 isoforms of NOS?
nNOS, eNOS, iNOS
what is nNOS?
localised primarily in CNS+ PNS
acts as neurotransmitter
where’s eNOS found?
endothelial cells, epithelial cells etc.
What’s iNOS?
the only calcium independent NOS
controls vascular tone
what inflammatory responses do histamine and serotonin give? (2)
vasodilation
vascular permeability
what inflammatory responses do prostaglandins give? (3)
vasodilation
fever
pain
what inflammatory responses does NO give? (1)
vasodilation
what inflammatory response do complement proteins give? (3)
vascular permeability
chemotaxis
leukocyte recruitment/activation
what inflammatory response do leukotrienes give? (3)
vascular permeability
chemotaxis
leukocyte recruitment/activation
what inflammatory response do interleukins give? (3)
- chemotaxis
- leukocyte recruitment/activation
- fever
what inflammatory response do chemokines give? (2)
chemotaxis
leukocyte recruitment/activation
what inflammatory response do leukotrienes give? (2)
chemotaxis
leukocyte recruitment/activation
what inflammatory response do bradykinins give? (1)
fever
what inflammatory response do lysosomal enzymes give? (1)
tissue damage
what inflammatory response do ROSes give? (1)
tissue damage
what inflammatory response does LTB4 give? (1)
tissue damage
give a very general summary of acute inflammation (4 steps)
recognise PAMPs/DAMPs
vascular changes- increased BF and permeability
attracting phagocytes and leukocytes
wide range of chemical mediators
