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Flashcards in Acute inflammation Deck (91):

what is acute inflammation

how cells respond to attack, it is a sudden response if tissue is damaged


why is acute inflammation a sudden response to damaged tissue

to prevent the spread of infection e.g. bacteria & clears away dead tissue


list why and how acute inflammation occurs

- response to injury
- needs to be fast
- limit risk of infection
- not a precise science unlike humeral response
- sets up pathway to wound healing


what is meant by acute inflammation not being a precise science unlike humeral response

it is not targeted to B & T cells , so some healthy cells get killed in the process


what is the purpose of tissue responses to damage

to eliminate dead tissue which is necrotic (becomes phagocatised)


what is acute inflammations initial response to tissue damage

to be able to defend the body


list the relatively non specific responses of acute inflammation

1. eliminate dead tissue (e.g. phagocytosis)
2. protect against local infection (will be an area of neutrophils to defend the body)
3. allow immune system access (increased vascular permeability in the area to allow T & B cells to come in & target specific pathogens & begin the healing process led by macrophages)


what happens when acute inflammation allows the immune system to access

increased vascular permeability in the area to allow T & B cells to come in & target specific pathogens & begin the healing process led by macrophages


how does acute inflammation eliminate dead tissue



how does acute inflammation protect against local infection

will be an area of neutrophils to defend the body


list the causes of inflammation

- infection
bacteria (eg conjunctivitis = acute inflammation of conjunctiva)
- mechanical injury (e.g. blunt trauma)
- ischemia (causes an inflammatory response)
- chemical (e.g. burns)
- extremes of temperature
- radiation (UV)
- immune mechanisms (auto immune, may have acute inflammatory response e.g. seasonal hay fever)


list the 5 cardinal features of acute inflammation

1. rubor = redness
2. calor - heat
3. swelling (tumour)
4. dolor = pain
5. loss of function


what does rubor stand for



what does calor stand for



what is an example of swelling



what does dolor stand for



what is an important clinical sign of acute inflammation

swelling (tumour)


what must be increased to allow access for an immune response

vascular permeability


at which stage does edema occur following an injury during acute inflammation

0-1.5 days
involved in the first wave of defence


what occurs during edema

swelling of vessels becomes more leaky, as the fluid leaks out and into the area of injury, which enables entry of neutrophils


when does the entry of neutrophils to the injured sight occur during acute inflammation

0-2.5 days
involved in the first stage of defence


what do the neutrophils do

fight off infections or dead cells, clearing the decks which paves away for the macrophages


what are monocytes

found in the blood stream
once migrate, gets activated and becomes M1 or M2 type macrophages


what do macrophages do

set up wound healing, so lays down collagen & recruits other cells to help heal the area


the initial mediators of acute inflammation must be fast and so can be derived from which two things

1. cell membrane (a lot of initiated early inflammatory responses are derived from the cell membrane)
2. plasma (blood) - acute inflammatory response when get cut to decrease bleeding and protect the area & heal the wound


What are the cell derived mediators of acute inflammation

from cells, secreted or synthesised i.e. histamine from mast cell.
usually platelets, neutrophils, monocytes/macrophages and mast cells but mesochymal cells also possible


what is histamine

a powerful vasodilator which increases the vascular permeability very early & brings neutrophils in to protect


What are the plasma derived mediator of acute inflammation

inactive precursors in circulation ie complement proteins and kinins
(polypeptides of inactive proteins which circulate in the blood plasma & once its exposed to oxygen or collagen or the outside world, proteins and kinins becomes activated)


what are cell derived histamine & serotonin stored in and released from

- mast cells
- basophils
- platelets


what is the main purpose of mast cells, basophils and platelets

powerful vasodilators and increase vascular permeability


what is arachidonic acid

a fatty acid C-20 carbon chain found in the phospholipid membrane(/plasma membrane)


what does arachidonic acid produce



what is arachidonic acid present in

the membrane of the body's cells


what do eicosanoids contain

- prostaglandins
- thromboxanes
- leukotrienes


what do prostaglandins do

produces a feeling of fever & detects pain


what do thromboxanes do

'Clotting' regulates amount of permeability


what do leukotrienes do

'Leaky' increase vascular permeability


what do steroids inhibit

phospholipase, which knock out the mechanism of arachidonic acid


what do steroids suppress

initial acute inflammatory phase


what do COX-1 & COX-2 inhibitors, ASPIRIN, indomethacin inhibit



what does prostacyclin cause & inhibit

vasodilation, inhibits platelet aggregation


what does thromboxane cause

vasoconstriction, promotes platelet aggregation


what also increases vascopermeability

prostaglandin H2 (PGH2)


what does prostaglandin PGD2 & PGE2 cause

increased vascular permeability


what does leukotriene regulate

vasoconstriction, bronchospasm, when increased vascular permeability, so that the cell does not become too leaky = start & stop mechanism


list the three key points of arachidonic acid metabolism

- thromboxane 'clotting'
- prostaglandins 'pain'
- leukotrienes 'leaky'


outline what thromboxane 'clotting' regulates

platelet aggregation


outline what prostaglandins 'pain' regulates

- platelet disaggregation
- pain
- vasodilation


outline what leukotrienes 'leaky' regulates

- vasoconstriction
- neutrophil adhesion and chemotaxis
- slow action on increased vascular permeability into the area


what are cytokines

polypeptides (small proteins)


what are two important cytokines that are produced by cells

1. interleukin 1 (IL-1) & interleukin (IL-8)
2. tumour necrosis factor (TNF-alpha)


list the things that interleukins and TNF are responsible for

- increases leukocyte (white blood cells) adhesion to endothelial cells
- increases body temperature - fever by regulating hypothalamus
- degranulation of neutrophils
-attracts neutrophils to damaged areas


explain how interleukins & TNF are responsible for the degranulation of neutrophils

release their lysosomal content & reactive oxygen species to help destroy & liquify and pathogens


explain how interleukins & TNF attracts neutrophils to damaged areas

they act as chemical signals to other neutrophils to come into area of attack & draw neutrophils in e.g. act as signals to bring in more neutrophils


name a plasma derived mediators kinin

- bradykinin = potent vasodilator


what are and how do bradykinin (plasma derived kinin) work

- they are small peptides derived from plasma precursors
- are early short acting vasodilators that can cause pain
- activates complement system

(they are inactive in the blood plasma, but when the plasma comes in contact with collagen, kinin becomes activated and causes short acting vasodilation)


what initiates the kinin pathway

exposure of collagen to endothelial cells


what is the complement system made up of

a series of small proteins which interact with each other in response to help neutrophils find bacteria & destroy them


what is the complement system activated by

exposure to:
1. antigen - antibody complexes
2. mannose carbohydrates in oligosaccharides
3. pathogens


what are mannose found in



what is the complement activation for

to aid normal immune system


what do effector functions e.g. C5a and C3a: inflammation act as

cytokines to recruit more neutrophils into the area


when C3b is deposited onto the microbe, and once activated, what does it form



what does C3b also form

a complex with other proteins & forms the membrane attack complex, which clears microbes through recognition as it goes around & slices microbes & goes into microbes and the microbe explodes or gets phagocytosed or breaks down C3a & C5a & recruits macrophage neutrophils


list the cellular events in acute inflammation of neutrophils (how neutrophils get into area of infection)

1. margination
2. adhesion
3. emigration
4. chemotaxis (following C3a & C5a)
5. phagocytosis and degranulation (of neutrophil)


explain how margination occurs

- changes in haemodynamic flow (the way blood circulates)
- neutrophils align along the wall of endothelial cells (e.g. around edge of blood vessels or the bleeding person)
- and to emigrate in and to an open blood vessel & a tissue where there is acute inflammation occurring


explain how adhesion occurs

- once neutrophil is centred of into the periphery, need to adhere to cell membrane of endothelial cell bu:
1. E and P selections on endothelial cells
- lightly tether the leukocyte to the endothelial cell (i.e. it catches the neutrophil as it passes by and enters it & then gets an up regulation of P selectin which = stronger hold of P & E selectins binding to the neutrophil)
- binding to gylcoproteins on neutrophil
once those are locked in place, you get...
2. ICAM-1 on endothelial cell
- (intracellular adhesion molecule-1) bind to integrins receptors on neutrophil


what are the adhesion molecules E & P selectins

expressed on endothelial cells and bind to glycoprotein on surface of neutrophils


which out of E & P selections are the sticky ones

P selectin


what are P selectins stored in

weibel-palade bodies of endothelial cells


P selectins which are stored in the weibel-palade bodies relocate to the plasma membrane after...

stimulation by histamine and thrombin


what are P selectins released by

histamine and thrombin


what happens to P selectins if, theres a mast cell or increase basophil regulation

it increases P selectins which are regulated by histamine


what are weibel-palade bodies

cigar shaped organelles in endothelial cells that store P-selectins


what happens when endothelail cells which contain weibel-palade bodies are activate by histamine & thrombin

redistribution of P-selectin (i.e. it relocates to the cell membrane & can bind to neutrophils)


explain how emigration.migration occurs

1. requires firm adhesion by leukocyte and endothelial cell (P selectin, E selectin & ICAM1)
2. migration is mediated by PECAM-1
- platelet endothelial cell adhesion molecule
3. leukocyte passes between endothelial cells
4. leukocyte lies between endothelial cells - it releases collegenase/elastases to digest the endothelial basement membrane & get into the tissue


what does PCAM-1 do

opens up tight junctions between the endothelial cells and allows neutrophils to pass between the endothelial cells and enables passing between boundaries, allowing neutrophils into the extracellular space


explain how the continuation of migration - chemotaxis works

1. once in the endothelial cells, leukocytes migrate towards chemical signals
- examples of chemical signals are:
fragments of complement system (C5a),
prostaglandins and leukotrienes (products of arachidonic acid metabolism)


summerise the cellular events in acute inflammation of neutrophils

- leukocyte roles down and binds to P & E selectins which forms a cross linking which enables blocked sequence to be open
- so the integrin receptors break open due to E & P selectin by an intracellular signal which allows the integrin receptor to bind to ICAM1
- E & P selectin also grips the neutrophil & puts it next to the endothelial cell
- once got the whole integrity of ICAM1 with the P selectin holding the neutrophil down, it releases and manufactures PECAM-1 (CD31) on the endothelial adhesion molecule which breaks open the tight junctions and enables the neutrophil to squeeze through endothelial cells/emigrate from inside the blood vessel to tissue outside and looks for cytokines it can follow e.g. interleukins or C5a or C3a
- and carries neutrophils to area of injury


what happens once the neutrophil reaches the area of injury

once the neutrophil has escaped the compound, it is going to destruct and wants to kill bacteria, it is a non specific response so an acute immune response. so it will ingest any cell it comes across e.g. a C3b attached to a bacteria respiratory burst produces a lot of free radicals, so it depends on a good blood supply as its oxygen dependent


what disadvantage does neutrophils of a diabetic have

less ability to fight off bacteria because they don't have a good oxygen supply


name the two types of mechanisms for bacterial killing

1. oxygen dependent (respiratory burst)
2. oxygen independent (phagocytosis)


list the steps of phagocytosis 'the clear up'

- neutrophils or monocyte arrives at site of injury
- need to recognise the foreign material or dead cells
- need to ingest the debris and bacteria
- need to engulf the material


what are opsonins

factors that coat bacteria to enable recognition by neutrophils/macrophages for ingestion


what are the two key opsons

- immunoglobulin (IgG)
- C3b and component of complement


what happens in order for phagocytosis to ensue

neutrophil recognises IgG or C3b then phagocytosis ensues


list the phases of phagocytosis

1. chemotaxis and adherence of microbe to phagocyte
2. ingestion of microbe by phagocyte
3. formation of a phagosome
4. fusion of the phagosome with a lysosome to form a phagolysosome (which encapsulates organism we want to phagocytose)
5. digestion of ingested microbe by enzyme
6. formation of residual body containing indigestible material
7. discharge of waste materials
(indigestible waste material gets left behind and becomes scar tissue, and can end up in lymphatics and spleen/plasma which = pus discharge)


what are lysosomal contents

contents of neutrophils and monocytes that are contained in intracellular vesicles to protect the cells


what do lysosomal contents e.g. granules contain

1. lactoferrin - binds Fe (iron) and so reduces mitotic rate of bacteria
2. lysozyme - attacks cell wall or gram negative bacteria
3. collagenases - denature collagen & breaks up cellular degree
4. ellastases


what does the oxygen dependent mode of killing (the respiratory burst) produce

ROS (reactive oxygen species)


what can hypochlorous acid do

it is potent and can wipe out most bugs so for neutrophils to produce more hypochlorous acid can help to further protect the body from infection