9 - Pathogenesis of inflammatory disease Flashcards
what is inflammation
- response of living tissue to damaging stimuli
- directs immune components to site of damage
function is to containd damage and initiate repair processes to restore normal function
what are some causes on inflammation
- infection
- hypersensitivity reactions
- auto immunity
- trauma
- chemical/toxic
- radiation
classification of inflammation
acute (minutes or days)
- chronic (weeks or months)
signs of acute inflammation
- redness
- wamth
- pain
- swelling
- loss of function
what are the major features of acute inflammation
- vascular events
- cellular events
- triggered by inflammatory mediators which also perpetuate the inflammatory process
acute inflammation. major events VASCULAR
- Vasodilation (redness)
- increased blood flow (increased heat)
- increased vascular permeability ( contributes to oedema)
movement of inflammatory cells from blood vessels to site of injury - they minimise damage + initiate repair
extravasation of leukocytes(neutrophils) into tissues steps
neutrophils = phagocytes
- margination
- rolling.
- diapedesis
- chemotaxis
- margination
cell moves from centre of blood column to endothelial wall of blood vessels
- rolling
these white blood cells start rolling along the inner surface of the blood vessel.
endothelium has adhesion molecules, allowing inflamm. cell to attach
rolls along vessel wall before coming to rest
- diapedesis
cell squeezes through vessel wall - towards site of injury
- chemotaxis
once cell leaves vessel, able to move along conc. gradient of inflam. chemicals that are released from the site of inflammation
what is the role of phagocytes
to eliminate potential pathogens/ damaged tissues
phagocytosis
- phagocytes arrive at site of infammaton by chemotxcis
- attach to micro-organisms/cell deprsis of surface receptors
- material internalized + destroyed
- opsonization
inflammatory mediators
- vasoactive amines
- plasma proteases
- arachidonic acid metabolites
- cytokines
arachidonic acid pathway
this metabollic pathway generates a series of inflammatory mediators known as eicosanoids
process of eicasanoid synthesis
too long to write
what are mast cell mediators
- include pre formed and newly formed mediators
- pre formed incude: histamine, heparin, and neutral protease
newly formed: leukotrienes, prostoglandn
what do mast cell mediators have a role in
type 1 hypersensitivity reaction
where do MSM lie
close proximity to blood vessels
what do mast cells contain
granules containing pre formed mediators such as histamine and heparin
what happens when mast cells release the granules (degranulation)
histamine release - causes vasodilation and increases vascular permeability
what happens after degranulation
delayed second phase response (swelling/itching)
what are the outcomes of acute inflammation
1) complete resolution
2) scar formation
3) progress to chronic inflammation, mediated by lymphocytes and macrophages
what is the ocular response to inflammation
- redness
- could be consequence to heamorrhage. more likely vasodilation
redness varies in locaiton: diffused or localised
another ocular response to inflammation
oedema
what is oedema a consequence of
- ## increased vascular permeability #
exudates
another ocular response to inflammation
- increased vascular permeability
- rich in protein
- rich in inflammatory cells
cellular infiltration
- ocular response to inflammation
- sterile or non sterile
- acute (neutrophils)
- chronic )lymphocytes/macrophages)
what else can corneal infiltrates occur in response to
bacterial toxins e.g stappholococci
discharge
- ocular response
- serous (watery)
- mucopurolent
- plurulent
conjunctival papillae and follicles
- ocular response
- papillae common in allergic eye disease: each papilllae consists of dilated blood vessel at the centre with surrounding lymphocytes
- covered by hypotrophic endothelium
- follicles charecteristics of viral infection or toxic reaction
inflammation of the posterior segment
often chronic conditions
- anterior ischaemic optic neuropath
- sarcoidosis
ocular autoimmune diseases in the absence of systemic involvement
- moorens ulcer: causes a progressing thinning of peripheral cornea
- sympathetic ophtalmia - occurs due to penetrating injury to one eye followed by inflammation in other eye
ocular autoimmune disease with systemic involbement
-Reiter’s disease
-Ankylosing spondylitis
-Rheumatoid arthritis
-Behçet’ disease
-SLE
-Sjögren’s syndrome
-Sarcoidosis
-Cicatricial pemphigoid
what is the pathogensis of autoimmunity
- autoreactive T helper cells (CD4) often responsible for initiating tissue damage via production of cytokines
*autoreactive cytotoxic T cells (CD8) can also cause tissue damage
*antibodies cause tissue damage via a type II mechanism
pathogensis of allergic eye disease
- caused by type 1 or type IV hypersensitivity reaction
what type of reaction is acute allergic conjunctivitis and seasonal allergic conjunc.
type 1 hypersenitivity reaction
what reaction is atopic allergic conj. and giant papillary conjunc.
type IV
type 1 hypersenitivtiy is also referred to as?
atropy
what is type 1 hypersensitivity caused by
overproduction of igE
how is type 1 hypersensitivity triggered
- in minutes
- exposure to environmental antigens e.g pollen/dust mites
strong genetic link
type 1 mechanism
- mast cells have high affinity receptor for igE
- igE synthesised in response to certain allergens (antigens)
- allergens land on mucous membranes, then picked up by antigen presenting cells
- allergen is presented to TH2 cells which provide cytokine signals to B cells to produce more igE
- igE binds to mast cells
- if exposed to same allergen again, it binds to igE on the mast cell
- this causes degranulation
what happens in type 1 mechanism AFTER mast cell degranulation
- degrnaulation: mast cell release histamines/heparin
These cause itching, mucus secretion, vasodilation and oedema
type II hypersensitivity
- antibody directed against membrane and cell surface antigens
- antigen + antibody reactions activate complement producing membrane damage
type IV hypersensitivty - basics
- delayed type hypersensitivity
- takes more than 12 hours to develop after antigenic challenge
- T cell mediated mechanism
type 4 mechanism
- antigen presenting cells in conjunctiva pick up an antigen
- go to lymph nodes & activate T cells
- T cells go back to conjunctiva and produce cytokines + attract macrophages
- cause tissue damage
