Lecture 5 - Inflammation, Chemical Mediators Flashcards
mediators for vasodilation
PGE2, Histamine, NO
Mediators for vascular permeability
- histamine
- C3a, C5a
- bradykinin
- leukotriens C4, D4, E4, PAF
mediators of chemotaxis/activation
- chemokins (IL8
- C5a
- LTB4
4 microbial products - fibrinopeptides
1-3 are POTENT CHEMOTAXIS for neuts
mediators of fever
IL1, TNF alpha, PGE2
mediators of pain
bradykinin and PGE2
Mediators of tissue damage
lysosomal enzymes, oxygen radicals
__ is where one mediator can stimulate release of other mediators, mediators functions also __
amplifcation, overlap/redundant
what is important fact about mediators that is important in down regulating them
short lived
hageman factor (12) activates __
prekallikrein to kallikrein
kallikrein cleaves kininogen to __
bradykinin (remember kallikrein also activates plasmin for fibrionlysis)
__ acts to vasodilate, increase vascular permeability (leaky vessels), stimulates free nerve endings for PAIN, smooth muscle contraction
bradykinin
__ is complement fragment that is important for CHEMOTAXIS of neutrophils, mast cell degranulation, increased vascular perm
C5a
__ is complement fragment that increases vascular permeability
C3a (AND C5a)
__ is the most potent chemotaxtic substance for neutrophils
C5a
thrombin acts on fibrinogen to conver to fibrin and fibrinopeptides that are __
chemotaxtic for neuts and macs
Hageman factor (12) allows formation of __ and __ mediators and __ chemotaxins
bradykinin, C3a, fibrinopeptides
3 mediators from plasma
bradykinin, complement fragments, fibrionpeptides
what are the vasoactive amines
histamine and serotonin
sources of histamine
mast cells, basophils, platelets
histamine’s actions
vasodilation, increased venular perm, bronchial/smooth muscle contraction
leukotrienes (LTB) and prostaglandins are metabolites of
arachidonic acid
__ is important simulator of PAIN and inducer of FEVER
PGE2
__ and __ are cycloooxygenase products of arachdonic acid that increase vascular flow and perm = leaky vessels
PGE2 and PGD2
__ causes smooth m contraction in some tissues
PGD2
__ is one of the MOST POTENT neutrophil chemotaxis substances
Leukotriene B4 (LTB4)
Leukotriene B4 is chemokinesis for
macrophages
leukotrienes __ __ __ increase vascular perm and cause smooth m contraction
C4/D4/E4
cytokine __ comes from T cells and NK cells and is stimulated by Ag in early immune response to UPREGULATE/activate MACS
IFN gamma (important in type 4 hypersensativity)
Cytokine __ comes from macs, fibroblasts, and resident cell/tissue and is stimmulated by endotoxin, bacteria, virus, protozoa, and toxins to stimulate ENDOTHELIAL cell activity
TNF alpha
how does TNF alpha stimulate endothelial cell activity for leukocyte migration
upregulates E selectin and increases thrombogenicity
__ chemokines are chemotactic for neutrophils and endothelial cells
CXC (IL8 or CXCL8, PF4)
__ chemokines are chemotactic for lymphocytes, monocytes, and eosinophils
CC (MIP or CCL3, CCL5, CCL11)
EXAM: __ is highly chemotactic for neutrophils = one of the MOST POTENT for neutrophils (along with C5a and Leukotrein B4!!!)
CXCL8 or IL8
__ chemokines bring in neutrophils
CXCL8 or IL8
3 chemokines that bring in monocytes, macs, and t-lymphocytes
- CCL3/MIP
- CCL5/RANTES
- CCL7/MCP-3
chemokine that brings in eosinophils (allergies and parasites)
CL11/Eotaxin
__ is hallmark of chronic inflammation
fibrosis (fibroblasts, endothelial cells, collagen)
What inflammatory cells predominate in chronic inflammation
macs, lymphocytes, plasma cells (+/- neuts)
__ inflammation is dominated by macrophages
granulomatous
__ is a compact and organized collection of mononuclear inflammatory cells dominated by macs
granuloma
do all granulomatous inflammation lead to granuloma formation
no
what stimulates granulomatous inflammation
- things that resist lysosomal degradation and/or
- induce T cell hypersensitivity
stimuli: inert particles (silica), lipids, waxes, resistant microorgs (mycobacteria and fungi), high molec wt, Ag inducing T cell hypersensitivity
5 cells involved in granulomatous inflammatory reaction
- monocytes
- macrophages
- epitheloid cells
- multinucleated giants
- t lymphocytes
3 types of granulomatous inflamm reactions
- granulomatous inflammation (macs +/1 epithelioid cells, giant cells
- gimple granulomas (compact organized granulomatous inflamm cell exudate)
- complex granulomas (granuloma with centra necrosis +/- calcification)
what is the difference between simple and complex granuloma
complex granulomas have central necrosis +/- calcification
__ hypersensitivity is cell mediated by CD4 nad CD8 T-cells (tuberculosis, contact dermatitis, transplant regection)
type 4
cytokine important in activating macrophages to form epithelioid or giant cells during type 4 hypersensitivity reactions
IFN gamma (released by T cell)