Infection/Inflammatory response Flashcards
What are the key signs of inflammation?
heat
redness
swelling
pain
loss of function
describe the process of inflammation initiation
- microbe breaches barrier
- innate immune cells (macrophages, eutrophils, and dendritic cells) recognize ‘pathogen-associated molecular patterns’ (PAMP) using their ‘Pattern recognition receptors’ (PRR)
- once pathogen recognized, activate innate immune cells
- innate immune cells triger the production of cytokines and chemokines
- cytokines and chemokines initiate inflammaiton
*
What is the ‘Danger theory’ of tissue injury?
that cells (when damaged ) release self molecules, the “Danger signal” - these signals are then recognized by PRR and trigger the production of cytokines and chemokines - inflammaiton
What cause the key stages of inflammation?
redness/heat - caused by vasodilation
pain - caused by release of inflammatory mediators
swelling - cuased by increased permeability
in which (of the three) step of inflammation does activation of Macrophages, dendritic cells, and mast cells occur?
activation of tissue resident innate cells occurs in the first step of inflammation
in what stage of inflammation are cytokines, lipids, and proteins released?
Cytokines, lipids, and proteins like histamine are released in the first step
in what stage of inflammation does vasodilation and increased cell permeability occur?
in the second step - vasodilation and increased permeability allows for influx of neutrophils and monocytes
in what stage of inflammation does activation of neutrophils/monocytes occur?
activation of neutrophils and monocytes occures in the third step
in what stage of inflammation does redness, swelling, heat and pain occur?
in Step 3 - when the activation of neutrophils and monocytes releases cytokines
describe the functions of lipids as inflammatory mediators
lipid inflammatory mediators include prostaglandings, leukotrienes, platelet activating factors…
they are responsible for vasodilation and permeabilisaiton
describe the function of the cytokine inflammatory mediators
examples of cytokine inflammatory mediators are
IL1 and TNF alpha
they are responsible for activation, permeabilisation and cell adhesion
describe the function of chemokine inflammatory mediators
example of chemokine inflammaotry mediators = IL 8
they are responsible for chemoattraction
what chemical inflammatory mediators are there? What is their function?
Nitric oxide is a chemical inflammatory mediator - it is responsible for vasodilation
what protein inflammatory mediators are there? what is their function?
histamin and C5a are both protein inflammatory mediators - they are responsible for permeabilisation
what is the function of IL8?
IL-8 is a chemokine
chemokines are released by damaged cells and immune cells to bring more neutrophils to the infected region ‘chemoattractants’
they promote an increased expression of adhesion molecules on immune cells
what is ‘Extravasation?’
it is how cells know to leave the circulation and traffic to the site of infection
it is the increased expression of adhesion molecules on endothelial cells of blood vessels close to the site of infection that enables interaction between selectin (endothelial) and carbohydrate (neutrophil)
describe the key steps of extravasation
first step: loose binding between selectin (endothelial) and carbohydrate (neutrophil) enables neutrophils to slow down and ‘roll’ = rolling adhesion
second step = tight binding - facilitated by ICAM and integrin on the neutrophil
third step - neutrophil can ‘extravate’ through the vessel wall and into the surrounding tissue
what is the function of neutrophils and macrophages once they reach the infection site?
phagocytosis - engulfment and killing of microorganism
phagocytic neutrophils respond to an epithelial chemokine interleukin 8
what is the fist cell to migrate from the blood in the tissue into the underlying infection?
neutrophils are the first cells to migrate from the blood into the tissue underlying the infection - monocytes second
how does phagocytosis kill the microorganism?
using the NADPH oxidase mechanism- Lysosomal enzymes indirectly kill phagocytosed microbes by making reactive oxygen species and nitric oxide
-once it has been ‘eaten’ the microorganism experiences lysosomal enzymes which make antimicrobial peptides - which make super oxygen radials and nitric oxide- when they react it causes a ‘respiratory burst’
it’s essentially a miniture ‘chemical explosion’ of the cell
What is chronic granulomatous Disease?
phagocytes don’t function properly - leads to frequent severe infections of the skin, oral and intestinal mucosa
defect in NADPH oxidase system - a tissue biopsy may show granulomas -
Tests - nitroblue tetrazolium test - if NADPH oxidase is working then it will turn the WBC blue
how does our body terminate an acute inflammation?
- short life of neutrophils and inflammaotry mediators
- neutrophils undergo apoptosis - macrophages ingest
- macrophages will change character and promote repair
- release inhibitory cytokines (IL10 and TGFbeta)
- limit inflammation
- grwoth factors promote repair
- act on fibroblasts
- lipid mediators- switch to production of anti-inflammatory lipoxins, resolvins, and protectins
what causes chronic inflammation?
constant release of inflammatory mediators results in tissue injury - then macrophages constantly try to repair this ‘injury’ ending up with fibrosis of tissue instead of functional tissue
ex) COPD - lung fibrosis ,
Hepatitis = liver fibrosis
What are we seeing here?
liver fibrosis
fibrosis = blue
liver tissue= red
what characterises rheumatoid arthritis?
characterised by
- severe joint inflammation
- increased synovial fluid and thickened synovial membrane
- destruction of bone and cartilage in several joints
- elevated levels of pro-inflammatory cytokines
in the joints- lots of infiltrating macrophages and dendritic cells producing pro-inflmatory cytokines -
what inflammatory mediator is targeted by NSAIDs?
lipid inflammatory mediators - which are normally responsible for vasodilation and permeabilisation
what inflammatory mediator is targeted in anti-TNF therapies (etanercept or infliximab, as well as anti IL1 therapies like anakinra)
they target cytokines (hint anti - IL1) - which normally function to activate permeabilisation
