Mediators of Inflammation Flashcards
what is inflammation
response of vascularized tissue to physical, chemical or infection
brings cells and molecules of defence to area where they are required
what are the 5 Rs in inflammation
- recognition of offending agent
- recruitment of leukocytes and plasma proteins and activation of these
- removal of agents
- regulation = termination of reaction
- repair of damaged tissue
what are the benefits of inflammation
- dilution/inactivation of biological and chemical toxins
- killing/sequestering/degrading of microbes, foreign material, necrotic tissue and neoplastic cells
- providing wound healing factors
- restricting movement allowing for repair
- increasing temperatire to induce vasodilation and inhibit replication of pathogens
what are the consequences of inflammation
local tissue damage
harmful if misdirected, excessive/prolonged/difficult to control
or anti-inflammatory drugs
what is acute inflammation
onset: minutes or hours
neutrophils
innate immunity
usually mild and self-limited tissue injury
prominent local and systemic signs
what are the vascular effects of acute inflammation
- dilation
- congestion
- increased permeability (edema, plasma proteins, emigration of leukocytes from microcirculation)
what is the outcome of acute inflammation
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what are the features of chronic inflammation
days
lymphocytes, PC, adaptive immunity
often severe and progressive tissue injury, fibrosis
less local and systemic signs
what are the causes of chronic inflammation
persistent infection
hypersensitivity (auto-immune and allergy)
prolonged exposure to potential toxic agents (exogenous/endogenous)
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what are the mediators of acute inflammation
- vasoactive amines
- lipid products
- cytokines/chemokines
- complement proteins
where are mediators of acute inflammation secreted from
secreted by cells or produced in the liver
when are mediators produced
in response to stimuli
short lived
can stimulate release of other mediators
what cells are major produces of acute inflammation
macrophages, mast cells, dendritic cells
minor producers: platelets, neutrophils, endothelial cells, epithelial cells
what are histamines produced by
- mast cells
- blood basophils, platelets
when are histamines released
tramua, cold, heat
binding of anti-bodies (IgE) –> allergy
complement fragments C3a and C5a (anaphylatoxins)
what are the receptors of histamine
H1 on microvascular endothelial and
H2-H4
what are the results of histamine (7)
- dilation of arterioles
- increase of permeability of venules
- endothelial activation
- contraction of smooth muscle
- tachycardia
- eosinophil chemotaxis
- pain and pruritus
what are the inhibitors of histamine
H1-R-antagonist (in anti-histamines)
what are serotonies produced by
- platelets
- neuroendocrine cells
what are the result of serotonine
- vasoconstriction
- neurotransmitter in GIT
how are histamines and serotonine stored
as pre-formed molecules –> amongst first mediators to be released
what are arachnidonic acid metabolites
(eicosanoids)
- prostaglandins
- leukotriens
- lipotoxins
what are prostaglandins produced by
- mast cells
- macrophages
- endothelial cells
what are the inhibitors of prostaglandins
- aspirin
- NSAIDs
- selective COX2 inhibitors
what are the enzymes involved in the prostaglandin pathway
COX1 and COX2
what are leukotriens produced by
- mast cells
- leukocytes
what are the enzymes in leukotriens pathway
lipoxygenase (3 types)
what are inhibitors of leukotriens
5-lipoxygenase-inhibitor (LT-R antagonist)
what are lipoxins produced by
- leukocytes esp. neutrophils
- platelets
what enzymes are in the lipoxin pathway
lipoxygenase
what are the functions of lipoxins
anti-inflammatory due to inhibition of recruitment of leukocytes
what are the functions of arachidonic acid metabolites
- vasodilation: PGI2, PGE1, PGE2, PGD2
- vasoconstriction: TxA2, LTC4, LTD4, LTE4
- increased vascular permeability: LTC4, LTD4, LTE4
- chemotaxis, leukocyte adgesion: LTB4, HETE
- pain, fever: PG
what do steroids reduce
transcription of genes for PLA2 and COX2
what are cytokines of acute inflammation
TNF, IL-1
what are cytokines produced by
mainly by macrophages but also lymphocytes, dendritic cells, epithelial/endothelial/connective tissue cells
what is the function of cytokines
- endothelial activation (expression of adhesion molecules and mediators)
- leukocyte activation (response to stimuli and microbiocidal action)
- systemic acute phase response, including fever, and presence of cachexia
what are the inhibitors of cytokines
TNF-antagonists (esp for treatment of chronic conditions such as IBD), steroids
what are chemokines
chemoattractant for specific types of leukocytes
what are the four major groups of chemokines
- C lymphocytes
- CC monocytes, basophils, eosinophils, lymphocytes
- CXC neutrophils
- CX3C
what are the main functions of chemokines
- stimulation of leukocyte attachment to endothelium (via integrins)
- stimulation of leukocyte migration
- maintenance of tissue architecture (T and B cells in different areas of lymph node)
what are the inhibitors of chemokines
receptor antagonists
what are complement proteins
present in plasma in inactive form
what are complement proteins activated to form
activated to become proteolytic enzymes –> cascade
how is the complement protein pathway controlled
by cell associated and circulating proteins
what is the critical step in the complement protein pathway
the proteolysis of C3
what are the main functions of complement proteins (3)
- inflammation: C3a and C5a (anaphylatoxins) stimulate histamine release; C5a also chemotaxis for neutrophils, monocytes, eosinophils and activates lipoxygenase pathway
- opsonization and phagocytosis: C3b promotes phagocytosis by neutrophils and macrophages
- cell lysis: MAC complex (C5b-9)
what are the inhibitors of complement proteins
anti-C5 antibody
what are the functions of platelet-activating factors
vasoconstriction, bronchoconstriction
at low concentration: vasodilation, increased vascular permeability)
what are the functions of kinins such as bradykinin
increases vascular permeability
contraction of smooth muscle
dilation of blood vessels
pain
what are other examples of mediators of inflammation
neuropeptides like substance P and neuorkinin A
what are examples of mediators of chronic inflammation
cytokines (IL-12, IFN-y, IL-17, IL-4, 5, 13, 2)
what are cytokines of chronic inflammation produced by
lymphocytes and macrophages
what are the functions of cytokines
activation of cellular populations
what are TGF-B and IL-10
termination of immune response and induction of tissue repair and fibrosis