Path: Chemical Mediators of Inflammation
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- histamine
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most imp mediator
synthesized by basophils/ mast cells
vasodilator/ inc. vessel perm, important in anaphylactic shock, causes wheal and flare - serotonin
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released/ syn by basophils/mast cells/ platelets
synthesized from tryptophan
important in carcinoid syndrome - what is the fxn of serotonin?
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vasodilator/ inc. vessel permeability
neurotransmitter - what are the fxns of C3a/C5a?
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anaphylotoxins
directly stimulate histamine release from basophils/ mast cells
important in tissue swelling and shock - what is the fxn of C3b?
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opsinizing agent
neutrophils/monocytes/ macrophages have receptors - what does C5a do?
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anaphylotoxin and chemotactic agent
activates cascade that lead to LOX pathway
adhesion molecule synthesis on neutrophils - what does bradykinin do?
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stimulates vasodilation, inc. vessel permeability, and causes pain
also a bronchoconstrictor
cough and angioedema with ACE inhibitors - Tell me what you know about prostoglandins in general
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derived from arachadonic acid (called eiconisoids)
released from phospholipids in cell membranes by activation of phospholipase A2
synthesized from linoleic acid
*most prostoglandins are vasodilators/ inc. vessel permeability - what is Thromboxane A2 (TXA2)?
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PGH2 is converted by platelet-derived thromboxane synthase into TXA2
prodcut of arachadonic acid metabolism
TXB2 is the end product of its metabolism - What does TXA2 do?
- vasoconstricts and stimulates platelet aggregation
- How is prostacyclin (PGI2) made?
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PGH2 is converted by endothelial cell dervied prostacylclin synthase into PGI2
*prostacyclin synthase is not inhibited to any significant degree by aspirin and NSAIDs - what does PGI2 do?
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vasodilates
inhibits platelet aggregation - What does PGE2 do?
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*makes skin hypersensitive to pain
*vasodilates in kidney(blocked by NSAIDS, but not by acetominophen)
*Inc. renal blood flow
*Dec. renal absorption of Na
*inc. gastric mucosa blood flow
*activates osteoclasts
*imp in fever production
*inhibits platelet aggregation/IL-1 and IL2/leukocyte aggregation - what does PGF2a do?
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constricts uterine muscles
vasoconstricts/bronchoconstricts - what does PGD2?
- vasodilates and increases vessel permeability
- what does LTB4 do?
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adhesion molecule synthesis on neutrophils
chemotactic agent for neutrophils
*derived from arachodonic acid - What do LTC-D-E4 do?
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bronchoconstrict and vasoconstrict
important in asthma
* derived from AA - what does nitric oxide do?
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vasodilator/ increases vessel permeability
inportant in shock
*endothelial cell derived - What is the main Ig of acute inflammattion?
- IgM
- What is endothelin? what does it do?
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potent vaosconstrictor in endothelial cells
important in shock - What are the fxns of Hageman factor XII?
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activates intrinsic coagulation system
activates plasminogin in fibrolytic system
actiavates kinin system--> bradykinin prodxn
*important in the pathogenesis of disseminated intravascular coagulation (DIC) - What is the main Ig in chronic inflammation?
- IgG
- What are the functions of IL-1?
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*fever: stimulates PGE2 synthesis in anterior hypothalamus
*B Cell stimulation to synthesize Igs
*activates osteoclasts
*increases adhesion molecule synthesis by endothelial cells
*increases liver synthesis of acute phase reactants - what does interferon-y do?
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activates macrophages to kill microbial pathogens
antiviral activity
induces MHC antigens
increases production of IL-2 and IL-12 by CD4-T helper cells
* produced by CD4 T helper cells - IL-2: source and fxn?
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made by CD4 T helper cells
primarily a T cell growth factor
promotes B cell/ NK cell proliferation - IL-3: source and fxn?
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T cells, thymic epithelial cells
stimulates proliferation of T cells, B cells, and NK cells
activates monocytes
increases hematopoiesis - IL-4: source and fxn?
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activated T Cells
mainly promotes growth of B Cells
enhances expression of HLA class II antigens
switch of IgM synthesis in B cells to IgE syn in type I hypersensitivity rxns - IL-5: source and fxn?
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T cells and mast cells
promotes end stage maturationof B cells into plasma cells
IgE synthesis, growth of eosinophils - IL-6: source and fxn?
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T cells, monocytes/macrophages, others
promotes maturation of B and T cells
inhibits growth of fibroblasts
stimulates synthesis of acute phase reactants in liver in acute inflammation - IL-12: source and fxn?
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macrophages
promotes growth of CD8 T cells
differentiation of CD4 T helper cells into Th1 and Th2 classes
- imp in granuloma formation
- imp in prodxn of memory T cells
promotes interferon-y production
enhances NK activity - Interferon-alpha (IFN-a): source and fxn?
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B cells and macrophages
antivral activity - IFN-B: source and fxn?
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Fibroblasts
antiviral activity - Tumor Necrosis Factor-a (cahectin): source and fxn?
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macrophages, T cells, and NK cells
Stimulates T cell proliferation and IL-2 production, cytotoxic to some tumor cells - TNF-B:source and fxn?
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T cells
Stimulates T cell
proliferation and IL-2 production, cytotoxic to some tumor cells - What vasoactive mediator mediates vasoconstriction?
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TxA2
LTC4, LTD4, LTE4
PAF - What vasoactive mediator mediates vasodilation?
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PGI2
PGD2, PGE2, PGF2a
Bradykinin
PAF - What vasoactive mediator mediates Increased vascular permeability?
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Histamine
serotonin
PGD2, PGE2, PGF2a
LTC4, LTD4, LTE4
bradykinin
PAF
Nitric oxide