acute and chronic inflammation part 1 Flashcards by Sana Rana

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

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what are the 5 carinal signs of inflammation

calor/warmth
rubor/ redness/ erythema  
tumor/ swelling/ oedema 
dolor/ pain
functino laesa/ lack of function

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what did john hunter propose

that inflammation wasn’t a disease but a response to tissue injury

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when did john hunter propose this idea

late 18th century

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who introduced the idea of functino laesa

ruodolf virchow- the father of pathology

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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.

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what are souces of mediators

nitric acid
histamines
cytokines

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what do PMN leukocytes do

elimination of microbes and dead tissue

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what do extra cellular proteins matrix do

repair

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when is an inflammatory reaction triggered

induced by chemical mediators that are produced by host cells in response to injurious stimuli

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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

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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

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what do we call the immune complex if it is self

auto immune complex

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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

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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)

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what does thermal injury lead to sometimes

tissue necrosis

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what is the onset of acute inflammation

fast min hours

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what is the duration of acute inflammation

short few mins- few days

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what are the infiltrating cells in acute inflammation

PMNS and macrophage

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what type of injury is caused in acute

self limiting

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what are the local systemic signs of acute inflmmation

prominent

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what is the onset of chronic inflammation

slow, days

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what is the duration of chronic inflammation

variable

possible months and years

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what are the infiltrating cells in chronic inflammation

macrophage and lymphocyte due to the fact adaptive immune system to contribute

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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

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.