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Module 7 > Mediators of Inflammation > Flashcards

Mediators of Inflammation Flashcards

1
Q

what is inflammation

A

response of vascularized tissue to physical, chemical or infection

brings cells and molecules of defence to area where they are required

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2
Q

what are the 5 Rs in inflammation

A
  1. recognition of offending agent
  2. recruitment of leukocytes and plasma proteins and activation of these
  3. removal of agents
  4. regulation = termination of reaction
  5. repair of damaged tissue
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3
Q

what are the benefits of inflammation

A
  1. dilution/inactivation of biological and chemical toxins
  2. killing/sequestering/degrading of microbes, foreign material, necrotic tissue and neoplastic cells
  3. providing wound healing factors
  4. restricting movement allowing for repair
  5. increasing temperatire to induce vasodilation and inhibit replication of pathogens
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4
Q

what are the consequences of inflammation

A

local tissue damage

harmful if misdirected, excessive/prolonged/difficult to control

or anti-inflammatory drugs

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5
Q

what is acute inflammation

A

onset: minutes or hours

neutrophils

innate immunity

usually mild and self-limited tissue injury

prominent local and systemic signs

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6
Q

what are the vascular effects of acute inflammation

A
  1. dilation
  2. congestion
  3. increased permeability (edema, plasma proteins, emigration of leukocytes from microcirculation)
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7
Q

what is the outcome of acute inflammation

A
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8
Q

what are the features of chronic inflammation

A

days

lymphocytes, PC, adaptive immunity

often severe and progressive tissue injury, fibrosis

less local and systemic signs

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9
Q

what are the causes of chronic inflammation

A

persistent infection

hypersensitivity (auto-immune and allergy)

prolonged exposure to potential toxic agents (exogenous/endogenous)

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10
Q

what are the mediators of acute inflammation

A
  1. vasoactive amines
  2. lipid products
  3. cytokines/chemokines
  4. complement proteins
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11
Q

where are mediators of acute inflammation secreted from

A

secreted by cells or produced in the liver

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12
Q

when are mediators produced

A

in response to stimuli

short lived

can stimulate release of other mediators

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13
Q

what cells are major produces of acute inflammation

A

macrophages, mast cells, dendritic cells

minor producers: platelets, neutrophils, endothelial cells, epithelial cells

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14
Q

what are histamines produced by

A
  1. mast cells
  2. blood basophils, platelets
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15
Q

when are histamines released

A

tramua, cold, heat

binding of anti-bodies (IgE) –> allergy

complement fragments C3a and C5a (anaphylatoxins)

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16
Q

what are the receptors of histamine

A

H1 on microvascular endothelial and

H2-H4

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17
Q

what are the results of histamine (7)

A
  1. dilation of arterioles
  2. increase of permeability of venules
  3. endothelial activation
  4. contraction of smooth muscle
  5. tachycardia
  6. eosinophil chemotaxis
  7. pain and pruritus
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18
Q

what are the inhibitors of histamine

A

H1-R-antagonist (in anti-histamines)

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19
Q

what are serotonies produced by

A
  1. platelets
  2. neuroendocrine cells
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20
Q

what are the result of serotonine

A
  1. vasoconstriction
  2. neurotransmitter in GIT
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21
Q

how are histamines and serotonine stored

A

as pre-formed molecules –> amongst first mediators to be released

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22
Q

what are arachnidonic acid metabolites

A

(eicosanoids)

  1. prostaglandins
  2. leukotriens
  3. lipotoxins
23
Q

what are prostaglandins produced by

A
  1. mast cells
  2. macrophages
  3. endothelial cells
24
Q

what are the inhibitors of prostaglandins

A
  1. aspirin
  2. NSAIDs
  3. selective COX2 inhibitors
25
what are the enzymes involved in the prostaglandin pathway
COX1 and COX2
26
what are leukotriens produced by
1. mast cells 2. leukocytes
27
what are the enzymes in leukotriens pathway
lipoxygenase (3 types)
28
what are inhibitors of leukotriens
5-lipoxygenase-inhibitor (LT-R antagonist)
29
what are lipoxins produced by
1. leukocytes esp. neutrophils 2. platelets
30
what enzymes are in the lipoxin pathway
lipoxygenase
31
what are the functions of lipoxins
anti-inflammatory due to inhibition of recruitment of leukocytes
32
what are the functions of arachidonic acid metabolites
1. vasodilation: PGI2, PGE1, PGE2, PGD2 2. vasoconstriction: TxA2, LTC4, LTD4, LTE4 3. increased vascular permeability: LTC4, LTD4, LTE4 4. chemotaxis, leukocyte adgesion: LTB4, HETE 5. pain, fever: PG
33
what do steroids reduce
transcription of genes for PLA2 and COX2
34
what are cytokines of acute inflammation
TNF, IL-1
35
what are cytokines produced by
mainly by macrophages but also lymphocytes, dendritic cells, epithelial/endothelial/connective tissue cells
36
what is the function of cytokines
1. endothelial activation (expression of adhesion molecules and mediators) 2. leukocyte activation (response to stimuli and microbiocidal action) 3. systemic acute phase response, including fever, and presence of cachexia
37
what are the inhibitors of cytokines
TNF-antagonists (esp for treatment of chronic conditions such as IBD), steroids
38
what are chemokines
chemoattractant for specific types of leukocytes
39
what are the four major groups of chemokines
1. C lymphocytes 2. CC monocytes, basophils, eosinophils, lymphocytes 3. CXC neutrophils 4. CX3C
40
what are the main functions of chemokines
1. stimulation of leukocyte attachment to endothelium (via integrins) 2. stimulation of leukocyte migration 3. maintenance of tissue architecture (T and B cells in different areas of lymph node)
41
what are the inhibitors of chemokines
receptor antagonists
42
what are complement proteins
present in plasma in inactive form
43
what are complement proteins activated to form
activated to become proteolytic enzymes --\> cascade
44
how is the complement protein pathway controlled
by cell associated and circulating proteins
45
what is the critical step in the complement protein pathway
the proteolysis of C3
46
what are the main functions of complement proteins (3)
1. inflammation: C3a and C5a (anaphylatoxins) stimulate histamine release; C5a also chemotaxis for neutrophils, monocytes, eosinophils and activates lipoxygenase pathway 2. opsonization and phagocytosis: C3b promotes phagocytosis by neutrophils and macrophages 3. cell lysis: MAC complex (C5b-9)
47
what are the inhibitors of complement proteins
anti-C5 antibody
48
what are the functions of platelet-activating factors
vasoconstriction, bronchoconstriction at low concentration: vasodilation, increased vascular permeability)
49
what are the functions of kinins such as bradykinin
increases vascular permeability contraction of smooth muscle dilation of blood vessels pain
50
what are other examples of mediators of inflammation
neuropeptides like substance P and neuorkinin A
51
what are examples of mediators of chronic inflammation
cytokines (IL-12, IFN-y, IL-17, IL-4, 5, 13, 2)
52
what are cytokines of chronic inflammation produced by
lymphocytes and macrophages
53
what are the functions of cytokines
activation of cellular populations
54
what are TGF-B and IL-10
termination of immune response and induction of tissue repair and fibrosis

Module 7 (50 decks)

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