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410 Cards in this Set
- Front
- Back
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what are the three major components of acute inflammation?
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1) alterations in vascular caliber that lead to increased blood flow
2) structural changes in microvasculature that permit plasma proteins and leukocytes to leave circulation 3) emigration of leukocytes from microcirculation, their accumulation in the focus of injury, and their activation |
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what are toll-like receptors?
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receptors that detect bacteria, viruses, and fungi
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what molecules, released from necrotic cells elicit inflammation?
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uric acid (purine metabolite)
ATP HMGB-1 (DNA binding protein of unknown function) DNA (when released into cytoplasm) |
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what is the effect of hypoxia on inflammation?
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is an inducer of the inflammatory response
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how does hypoxia induce the inflammatory response?
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hypoxia-induced factor-1alpha (HIF-1alpha)
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what cells produce HIF-1alpha?
what is its effect? |
cells deprived of oxygen
activates transcription of many genes involved in inflammation, including VEGF |
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why do foreign bodies elicit inflammation?
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cause traumatic injury
carry microbes |
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what is exudation?
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the escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities
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what is an exudate?
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extravascular fluid that has a high protein concentration, contains cellular debris, and has a high specific gravity
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what is implied by the presence of exudate?
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increase in the normal permeability of small blood vessels in an area of injury, and therefore an inflammatory reaction
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what is a transudate?
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extravascular fluid with low protein content (most of which is albumin), little or no cellular material, and low specific gravity
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what causes a transudate?
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osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability
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what is edema?
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excess of fluid in the interstitial tissue or serous cavities
can be either transudate or exudate |
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what is pus?
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a purulent exudate
inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells, and in many cases, microbes |
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what vasculature is involved in vasodilation?
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first the arterioles
then leads to opening of new capillary beds in the area |
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what is erythema?
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heat and redness caused by increased blood flow at the site of inflammation
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what two mediators are notable for causing vasodilation by their actions at vascular smooth muscle?
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histamine
nitric oxide (NO) |
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what is the result of loss of fluid and increased vessel diameter in vasculature during inflammation?
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slower blood flow
concentration of red cells in small vessels increased viscosity of blood |
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what is stasis?
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dilation of small vessels that are packed with slowly moving red cells
seen as vascular congestion upon examination of the involved tissue |
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what happens as stasis develops?
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red blood cells accumulate in the middle of the blood flow
leukocytes, principally neutrophils, accumulate along the vascular endothelium endothelial cells are activated by mediators produced at sites of infection and tissue damage, and express increased levels of adhesion molecules |
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what mechanisms are responsible for increased vascular permeability in acute inflammation?
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1) contraction of endothelial cells resulting in increased interendothelial spaces
2) endothelial injury, resulting in endothelial cell necrosis and detachment 3) increased transport of fluids and proteins through the endothelial cell (transcytosis) |
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what is transcytosis?
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transport of fluids and proteins through the endothelial cells
occurs in venules induced by VEGF |
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what chemical mediators cause contraction of endothelial cells resulting in increased interendothelial spaces?
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histamine
bradykinin leukotrienes neuropeptide substance P |
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what is the immediate transient response in vascular permeability? why?
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contraction of endothelial cells resulting in increased interendothelial spaces
it occurs rapidly after exposure to the mediator and is usually short-lived (15-30 minutes) |
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when is direct damage to vascular endothelium encountered?
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severe injuries
- burns - actions of microbes that target endothelial cells |
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what is lymphangitis?
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inflammation of lymphatics
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what is lymphadenitis?
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inflammation of lymph nodes
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why are inflamed lymph nodes often enlarged?
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hyperplasia of the lymphoid follicles
increased number of lymphocytes and macrophages |
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of what are red streaks near a skin wound a tell tale sign?
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infection in the wound
follows lymphatic channels and is diagnostic of lymphangitis |
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what are the most important leukocytes in typical inflammatory reactions?
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phagocytes (neutrophils and macrophages)
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what steps must a leukocyte undergo in the lumen of a blood vessel before extravasation?
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margination
rolling adhesion to endothelium |
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how are blood cells oriented in normally flowing blood in venules?
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red cells are confined to a central axial column displacing leukocytes toward the wall of the vessel
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what is the effect, on white blood cells, of stasis in inflammation?
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wall shear stress decreases and more white cells assume a peripheral position along the endothelial surface
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what is margination?
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leukocyte redistribution to a peripheral position along the endothelial surface as an effect of stasis
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what is rolling, as it refers to extravasation?
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leukocytes (first individually, and then in rows) adhere transiently to the endothelium, detach and bind again as they travel along the vessel wall
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by what family of proteins are the initial rolling interactions of leukocytes mediated?
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selectins
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what are the three types of selectins? on what cells are they expressed?
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L-selectin on leukocytes
E-selectin on endothelial cells P-selectin on platelets and endothelial cells |
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what are the ligands for selectins?
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sialylated oligosaccharides bound to mucin-like glycoprotein backbones
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what regulates the expression of selectins and their ligands?
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cytokines produced in response to infection and injury
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what is the effect of TNF on endothelial cells?
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in the post-capillary venules, TNF induces the endothelial cells to express numerous adhesion molecules
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what is the effect of IL-1 on endothelial cells?
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in the post-capillary venules, it induces the expression of adhesion molecules
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what adhesion molecules are expressed by endothelial cells when they are stimulated with TNF?
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E-selectin
ligands for L-selectin (GlyCam-1, CD34) VCAM-I ICAM-I |
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what adhesion molecules are expressed by endothelial cells when they are stimulated with IL-1?
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E-selectin
ligands for L-selectin (GlyCam-1, CD34) VCAM-I ICAM-I |
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what chemical mediators induce the redistribution of P-selectin from Weibel-Palade bods to he cell surface?
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histamine
thrombin platelet-activating factor (PAF) |
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at are the endothelial cell granules called where P-selectin is normally stored intracellularly?
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Weibel-Palade bodies
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where do leukocytes express L-selectin?
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tips of their microvilli
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what adhesion molecules are expressed on leukocytes to bind when they are rolling?
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L-selectin
ligands for E- and P-selectins (sialyl-lewis X-modified proteins) |
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why do selectins mediate rolling and not strong adhesion of leukocytes?
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they are low affinity interactions with their complementary molecules and have fast off-rates
the interactions are easily disrupted by the flowing blood |
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what family of heterodimeric leukocyte surface proteinsmediates firm adhesion?
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integrins
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what is VCAM-I?
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vascular cell adhesion molecule-I
ligand for VLA-4 integrin important in firm adhesion of eosinophils, monocytes, and lymphocytes |
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what is ICAM-I?
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intercellular adhesion molecule-I
ligand for LFA-I and Mac-I integrins important in firm adhesion, arrest, and transmigration of neutrophils, monocytes, and lymphocytes |
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what is the endothelial ligand for the VLA-4 integrin on leukocytes?
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VCAM-I
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what is the endothelial ligand for the LFA-1 integrin on leukocytes?
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ICAM-1
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what is the endothelial ligand for the Mac-1 integrin on leukocytes?
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ICAM-1
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what selectin molecules are expressed on endothelial cells?
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E-selectin
P-selectin |
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what selectin molecules are expressed on platelets?
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P-selectin
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what selectin molecules are expressed on leukocytes?
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L-selectin
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in what state are integrins normally expressed on leukocytes?
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low affinity state
activation of leukocytes with chemokines leads to a conversion of VLA-4 and LFA-1 to a high-affinity state |
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what is transmigration?
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aka diapedesis
migration of the leukocytes through the endothelium |
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where does transmigration of leukocytes mainly occur?
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post-capillary venules
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what is CD31?
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aka PECAM-1 (platelet endothelial cell adhesion molecule-1)
adhesion molecule present in the intercellular junctions between endothelial cells, that is involved in migration of leukocytes |
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how do leukocytes pierce the basement membrane after traversing endothelium?
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by secreting collagenases
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how are leukocytes able to adhere to extracellular matrix in connective tissue?
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integrins
CD44 retains leukocytes at the site where they are needed |
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what is the defect in leukocyte adhesion deficiency type 1?
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defect in biosynthesis of the beta2 chain shared by the LFA-1 and Mac-1 integrins
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what is the defect in leukocyte adhesion deficiency type 2?
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defect in fucosyl transferase
causes absence of sialyl-lewis x antigen, ligand for E- and P-selectins |
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what is the function of fucosyl transferase?
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enzyme that attaches fucose moieties to protein backbones
important for synthesizing sialyl-lewis x antigen, the ligand for E- and P- selectins |
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what is chemotaxis?
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locomotion along a chemical gradient
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what are the most common exogenous chemoattractants?
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bacterial products, including peptdes that possess an N-formylmethionine terminal amino acid
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what are endogenous chemoattractants?
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cytokines (e.g. IL-8)
components of complement system (e.g. C5a) arachidonic acid metabolites (e.g. LTB4) |
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how does chemotaxis occur?
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chemotactic molecule binds receptor -> activation of second messengers -> inc. cytosolic calcium -> activated guanosine triphosphatases of the Rac/Rho/cdc42 family -> polymerization of actin at leading edge; myosin filaments localized in back
filopodia pull the back of the cell in the direction of extension |
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what types of leukocytes predominate the infiltrate of acute inflammation?
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neutrophils during first 6-24 hours
monocytes in 24-48 hours |
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why are neutrophils quicker to respond than other leukocytes?
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more numerous in the blood
respond more rapidly to chemokines attach more firmly to rapidly induced adhesion molecules (E- and P- selectins) |
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what happens to neutrophils 24-48 hours after they enter the tissues?
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undergo apoptosis and disappear
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why do monocytes become the dominant population of leukocytes in chronic inflammatory reactions?
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neutrophils undergo apoptosis and disappear after 24 to 48 hours
monocytes survive longer and may proliferate in the tissues |
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by what type of leukocyte is the infiltrate in a pseudomonas infection dominated?
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continuously recruited neutrophils for several days
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what type of leukocyte is the first in the infiltrate in viral infections?
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lymphocytes
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what are the main leukocytes to arrive at a hypersensitivity reaction?
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eosinophils
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what type of receptors recognize short bacterial peptides containing N-formylmethionyl residues? on what cells?
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G protein-coupled receptors
on neutrophils, macrophages, and most other leukocytes |
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what receptor, expressed by phagocytes, recognizes breakdown products of C3?
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type 1 complement receptor (CR1)
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what is the major macrophage-activating cytokine?
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interferon-gamma (IFN-gamma)
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what cells secrete IFN-gamma?
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natural killer cells reacting to microbes
antigen-activated T lymphocytes during adaptive immune responses |
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leukocyte activation results from signaling pathways that are triggered in leukocytes, resulting in...
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increases in cytosolic calcium
activation of enzymes such as protein kinase C and phospholipase A2 |
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what are the functional responses that are most important for destruction of microbes?
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phagocytosis
intracellular killing |
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what is the macrophage mannose receptor?
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a lectin that binds terminal mannose and fucose residues of glycoproteins and glycolipids
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how do the terminal sugars of microbial cell walls differ from that of mammals?
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microbes have mannose and fucose residues on glycoproteins and glycolipids
mammals have sialic acid or N-acetylgalactosamine |
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what are bound by macrophage scavenger receptors?
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variety of microbes in addition to modified LDL particles
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what is the function of macrophage integrins, other than adhesion to endothelium?
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notably Mac-1 (CD11b/CD18)
binds microbes for phagocytosis |
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what are the major opsonins for microbes?
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IgG antibodies
C3b breakdown product of complement mannan-binding lectin |
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why is it a reasonable assertion to say that many of the same signals that trigger phagocytosis are many of the same that are involved in chemotaxis?
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both are dependent on polymerization of actin filaments
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by what types of molecules is microbial killing largely accomplished?
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reactive oxygen species
reactive nitrogen species |
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what causes the generation of reactive oxygen species?
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rapid assembly and activation of NADPH oxidase (aka phagocyte oxidase) which oxidizes NADPH and in the process, reduces oxygen to superoxide anion
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what is the respiratory burst?
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rapid oxidative reaction that produces superoxide anion from oxygen
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where are the different components of NADPH oxidase located in resting neutrophils?
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some are located in the plasma membrane and others are located in the cytoplasm
cytosolic components relocate to the phagosomal membrane in response to activating stimuli |
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how are the components of NADPH oxidase brought together?
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activating stimuli cause the cytosolic portions of the protein to migrate to the phagosome membrane where they assemble and form the functional enzyme complex
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how is superoxide mostly converted to hydrogen peroxide?
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mostly by spontaneous dismutation
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what is the function of myeloperoxidase?
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in the presence of a halide such as chloride, converts H2O2 to hypochlorite
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where is myeloperoxidase found?
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azurophilic granules of neutrophils
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why is it myeloperoxidase an important enzyme?
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H2O2 is not able to efficiently kill microbes by itself, but hypochlorite (end product of myeloperoxidase) is a potent antimicrobial agent
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what is halogenation?
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halide is bound covalently to cellular constituents
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what is the most efficient bactericidal system of neutrophils?
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H2O2-MPO-halide system
converts H2O2 and Cl to hypochlorite and water |
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from where is nitric oxide derived?
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NO is produced from arginine by the action of nitric oxide synthats (NOS)
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what are defensins?
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cationic arginine-rich granule peptides that are toxic to microbes
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what are cathelicidins?
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antimicrobial proteins found in neutrophils and other cells
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what is lysozyme?
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enzyme which hydrolyzes the muramic acid-N-acetylglucosamine bond, found in the glycopeptide coat of all bacteria
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what is major basic protein?
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a cationic protein of eosinophils, which has limited bactericidal activity but is cytotoxic to many parasites
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what are the two different methods by which macrophages can be activated?
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"classically activated" - strong microbicidal activity
"alternatively activated" - involved in tissue repair and fibrosis |
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what cytokines cause macrophages to be "alternatively activated"?
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IL-4
IL-13 (products of TH2 cells) |
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why are leukocytes dangerous to host as well as microbes?
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once leukocytes are activated, their effector mechanisms do not distinguish between offender and host
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w is frustrated phagocytosis?
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when phagocytes encounter materials that cannot be easily ingested (i.e. immune complexes deposited on immovable flat surfaces) causing strong activation
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what is chediak-higashi syndrome?
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autosomal recessive disease characterized by defective fusion of phagosomes and lysosomes, and abnormalities in melanocytes, abnormalities in the cells of the nervous system, and abnormalities in platelets
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what are the symptoms of chediak-higashi syndrome?
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susceptibility to infections
albinism nerve defects bleeding disorders neutropenia |
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what are the main leukocyte deffects in Chediak-Higashi syndrome?
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neutropenia (decreased number of neutrophils)
defective degranulation delayed microbial killing presence of giant granules (thought to result from aberrant phagolysosome fusion) |
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what is neutropenia?
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decreased number of neutrophils
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the defect in Chediak-Higashi syndrome is in the gene that encodes...
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LYST, a large cytosolic protein, thought to regulate lysosomal trafficking
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from what does chronic granulomatous disease result?
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inherited defects in the genes encoding components of phagocyte oxidase, which generates superoxide
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what are the most common variants of chronic granulomatous disease?
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x-linked defect in one of the membrane-bound components (gp91phox)
autosomal recessive defects in the genes encoding two of the cytoplasmic components (p47phox and p67phox) |
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what gives chronic granulomatous disease its name?
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macrophage-rich chronic inflammatory reaction tries to control the infection when the initial initial neutrophil defense is inadequate
this leads to collections of activated macrophages that wall off the microbes, forming aggregates called granulomas |
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what two types of cells are resident in tissues and serve important functions in initiating acute inflammation?
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mast cells
macrophages |
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what are sentinel cells?
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cells resident in tissues that rapidly recognize potentially injurious stimuli and initiate host defense reaction
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to what do mast cells react?
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physical trauma
breakdown products of complement microbial products neuropeptides |
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what is released by mast cells?
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histamine
leukotrienes enzymes TNF IL-1 chemokines |
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why does inflammation decline?
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mediators of inflammation are produced in rapid bursts, only as long as the stimulus persists, have short half-lives, and are degraded after their release
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what are the four stop signals triggered by the development of inflammation?
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switch in type of arachidonic acid metabolite produced
liberation of anti-inflammatory cytokines production of anti-inflammatory lipid mediators neural impulses (cholinergic discharge) |
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what arachidonic acid metabolites are proinflammatory and which are antiinflammatory?
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proinflammatory - leukotrienes
antiinflammatory - lipoxins |
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what are the antiinflammatory cytokines?
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transforming growth factor-beta (TGF-beta)
IL-10 |
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what are the anti-inflammatory lipid mediators?
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resolvings
protectins |
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what is the effect of neural impulses on the acuteinflammatory response?
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neural impulses = cholinergic discharge
inhibits production of TNF in macrophages |
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where are plasma proteins produced?
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mainly in the liver
present in circulation as inactive precursors that must be activated |
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what are the vasoactive amines?
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histamine
serotonin |
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how are vasoactive amines stored?
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includes histamine and serotonin
stored as preformed molecules in cells, and are therefore among the first mediators to be released during inflammation |
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what is the richest sources of histamine?
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mast cells in connective tissue adjacent to blood vessels
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in what cells is histamine found?
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mast cells
blood basophils platelets |
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histamine is present in mast cell granules and is released in response to what?
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1) physical injury (trauma/heat/cold)
2) binding of IgE antibodies to mast cells 3) fragments of complement called anaphylatoxins (C3a and C5a) 4) histamine releasing proteins derived from leukocytes 5) neuropeptides (substance P) 6) cytokines (IL-1, IL-8) |
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what is considered to be the principle mediator of the immediate transient phase of increased vascular permeability?
|
histamine
|
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what are the effects of histamine?
|
vasodilation
increased vascular permeability endothelial activation |
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what are the principal cell-derived mediators of inflammation?
|
histamine
serotonin prostaglandins leukotrienes platelet activating factor reactive oxygen species nitric oxide cytokines (TNF, IL-1) chemokines |
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what are the principal plasma protein-derived mediators of inflammation?
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complement products (C5a, C3a, C4a)
kinins proteases activated during coagulation |
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what are the principal sources of histamine?
|
mast cells
basophils platelets |
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what are the principal sources of serotonin?
|
platelets
|
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what are the principal sources of prostaglandins?
|
mast cells
leukocytes |
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what are the principal sources of leukotrienes?
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mast cells
leukocytes |
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what are the principal sources of platelet-activating factor?
|
leukocytes
mast cells |
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what are the principal sources of reactive oxygen species?
|
leukocytes
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what are the principal sources of nitric oxide?
|
endothelium
macrophages |
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what are the principal sources of TNF and IL-1?
|
macrophages
endothelial cells mast cells |
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what are the principal sources of chemokines?
|
leukocytes
activated macrophages |
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what are the principal sources of complement products?
|
plasma (produced in liver)
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what are the principal sources of kinins?
|
plasma (produced in liver)
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what are the principal sources of proteases activated during coagulation?
|
plasma (produced in liver)
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what are the actions of histamine?
|
vasodilation
increased vascular permeability endothelial activation |
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what are the actions of serotonin?
|
vasodilation
increased vascular permeability |
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what are the actions of prostaglandins?
|
vasodilation
pain fever |
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what are the actions of leukotrienes?
|
increased vascular permeability
chemotaxis leukocyte activation leukocyte adhesion |
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what are the actions of platelet-activating factor?
|
vasodilation
increased vascular permeability leukocyte adhesion chemotaxis degranulation oxidative burst |
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what are the actions of reactive oxygen species?
|
killing of microbes
tissue damage |
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what are the actions of nitric oxide?
|
vascular smooth muscle relaxation
killing of microbes |
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what are the actions of cytokines (TNF, IL-1)?
|
local endothelial activation (expression of adhesion molecules)
fever/painanorexia/hypotension decreased vascular resistance (shock) |
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what are the actions of chemokines?
|
chemotaxis
leukocyte activation |
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what are the actions of complement products (C5a, C3a, C4a)?
|
leukocyte chemotaxis and activation
vasodilation (mast cell stimulation) |
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what are the actions of kinins?
|
increased vascular permeability
smooth muscle contraction vasodilation pain |
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what are the actions of proteases activated during coagulation?
|
endothelial activation
leukocyte recruitment |
|
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by what receptors are the vasoactive effects of histamine mediated?
|
H1 receptors on microvascular endothelial cells
|
|
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what is another name for serotonin?
|
5-hydroxytryptamine
|
|
|
in what cells is serotonin found?
|
platelets
certain neuroendocrine cells (GI tract) |
|
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when is release of serotonin from platelets stimulated?
|
when platelets aggregate after contact with collagen, thrombin, adenosine diphosphate, and antigen-antibody complexes
|
|
|
what type of fatty acid is arachidonic acid?
|
20-carbon polyunsaturated fatty acid
5,8,11,14-eicosatetraenoic acid |
|
|
from what sources is arachidonic acid derived?
|
dietary sources
or conversion from the essential fatty acid, linoleic acid |
|
|
how is arachidonic acid usually found in the cell
|
esterified in membrane phospholipids (not free in the cell)
|
|
|
what enzyme releases arachidonic acid from membrane phospholipids?
|
phospholipase A2
|
|
|
what signals activate phospholipase A2?
|
increase in cytoplasmic calcium and activation of various kinases
|
|
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what are eicosanoids?
|
arachidonic acid-derived mediators
|
|
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what are the two classes of enzymes that synthesize eicosanoids?
|
cyclooxygenases (generate prostaglandins)
lipoxygenases (leukotrienes and lipoxins) |
|
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which class of enzymes creates prostaglandins from arachidonic acid?
|
cyclooxygenases
|
|
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which class of enzymes creates leukotrienes from arachidonic acid?
|
lipoxygenases
|
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which class of enzyme creates lipoxins from arachidonic acid?
|
lipoxygenases
|
|
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to what type of receptors do eicosanoids bind?
|
G protein-coupled receptor
|
|
|
what two enzymes produce cyclooxygenases?
|
COX-1 (constitutively expressed)
COX-2 (inducible) |
|
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which cyclooxygenase enzyme is constitutively expressed in tissues?
|
COX-1
|
|
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which cyclooxygenase enzyme is inducibly expressed in tissues?
|
COX-2
|
|
|
what are the most important prostaglandins in inflammation?
|
PGE2
PGD2 PGF2alpha PGI2 (prostacyclin) TXA2 |
|
|
what cells contain the enzyme, thromboxane synthetase?
|
platelets
TxA2 is a major product of these cells |
|
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what is the inactive form of TxA2?
|
TxB2
since TxA2 is unstable, it is rapidly converted into TxB2 |
|
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what are the effects of TxA2?
|
TxA2 is a potent platelet aggregating and vasoconstricting agent
|
|
|
what cells contain prostacyclin synthetase?
|
vascular endothelium
PGI2 is a major product of vascular endothelium |
|
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why does vascular endothelium produce prostacyclin, but not thromboxane?
|
vascular endothelium produces prostacyclin, because it expresses the enzyme, prostacyclin synthetase
it does not produce TxA2 because it does not express the enzyme, thromboxane synthetase |
|
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what is the major prostaglandin produced by platelets?
|
TxA2
|
|
|
what is the major prostaglandin produced by vascular endothelium?
|
PGI2 (prostacyclin)
|
|
|
what are the effects of prostacyclin?
|
vasodilation
potent inhibition of platelet aggregation markedly potentiates the permeability-increasing and chemotactic effects of other mediators |
|
|
what is the stable end product of prostacyclin?
|
PGF1alpha
|
|
|
what are the main prostaglandins produced by mast cells?
|
PGD2
PGE2 (more widely distributed) |
|
|
what are the effects of PGD2?
|
vasodilates and increases permeability of post-capillary venules, thereby potentiating edema formation
chemoattractant for neutrophils |
|
|
what are the effects of PGE2?
|
vasodilates and increases permeability of post-capillary venules, thereby potentiating edema formation
hyperalgesic - makes skin hypersensitive to painful stimuli |
|
|
what are the effects of PGF2alpha?
|
stimulates contraction of uterine and bronchial smooth muscle and small arterioles
|
|
|
what is the predominant lipoxygenase enzyme in neutrophils?
|
5-lipoxygenase
therefore LTB4 is the major leukotriene from neutrophils |
|
|
what reaction is catalyzed by 5-lipoxygenase?
|
arachidonic acid -> LTB4
as this is the major lipoxygenase enzyme in neutrophils, this is the major leukotriene produced by neutrophils |
|
|
what are the effects of LTB4?
|
potent chemotactic agent for neutrophils
potent activator of neutrophils (causing aggregation and adhesion to venular endothelium, generation of ROS, and release of lysosomal enzymes) |
|
|
what leukotrienes are cysteinyl-containing?
|
LTC4
LTD4 LTE4 |
|
|
what are the effects of LTC4?
|
intense vasoconstriction
bronchospasm increased vascular permeability |
|
|
what are the effects of LTD4?
|
intense vasoconstriction
bronchospasm increased vascular permeability |
|
|
what are the effects of LTE4?
|
intense vasoconstriction
bronchospasm increased vascular permeability |
|
|
where is the vascular leakage, caused by LTC4, LTD4, and LTE4, located?
|
restricted to venules
|
|
|
where is the vascular leakage, caused by histamine, located?
|
restricted to venules
|
|
|
which is more potent, leukotrienes or histamine?
|
leukotrienes are much more potent than is histamine in increasing vascular permeability and causing bronchospasm
|
|
|
what arachidonic acid products are inhibitors of inflammation?
|
lipoxins
|
|
|
how are lipoxins different from the other products of arachidonic acid metabolism (protaglandins and leukotrienes)?
|
1) lipoxins are inhibitors of inflammation, while the others are activators
2) two cell types are required for the biosynthesis of lipoxins, where only one is required for each of the others |
|
|
what two cell types are necessary to generate lipoxins from arachidonic acid?
|
leukocytes (particularly neutrophils)
platelets |
|
|
what is the process by which lipoxins are generated?
|
leukocytes (neutrophils) generate intermediates in lipoxin synthesis
platelets, interacting with the leukocytes convert these intermediates into lipoxins |
|
|
what are the principal actions of lipoxins?
|
inhibit leukocyte recruitment and the cellular components of inflammation
(inhibit neutrophil chemotaxis and adhesion to endothelium) |
|
|
how does aspirin inhibit cyclooxygenase enzymes?
|
irreversibly acetylates and inactivates them
|
|
|
why is COX-2 interesting as a therapeutic target?
|
it is induced by a variety of inflammatory stimuli
it is absent from most tissues under normal "resting" conditions |
|
|
what cyclooxygenase enzyme is responsible for the production of protaglandins that are involved in both inflammation and homeostatic functions?
|
COX-1
expressed contitutively in most tissues (this is not an absolute distinction; COX-2 does play a role in homeostasis) |
|
|
why is fish oil good for decreasing inflammatory status?
|
polyunsaturated fats in fish oil are poor substrates for conversion to active metabolites by the COX or the LOX pathways, but are excellent substrates for the production of resolvins and protectins
|
|
|
from what is platelet-activating factor derived?
|
phospholipid
|
|
|
in what cell types is platelet-activating factor (PAF) produced?
|
platelets
basophils mast cells neutrophils macrophages endothelial cells |
|
|
what are the effects of platelet-activating factor (PAF)?
|
platelet aggregation
vasoconstriction bronchoconstriction increased leukocyte adhesion to endothelium chemotaxis degranulation oxidative burst at extremely low concentrations: vasodilation increased venular permeability (100-10,000 times more potent than histamine) |
|
|
how does PAF cause increased leukocyte adhesion to endothelium?
|
enhances integrin-mediated leukocyte binding
|
|
|
what damaging responses in inflammation are caused by ROSs?
|
endothelial cell damage, with resultant increase in vascular permeability
injury to other cell types inactivation of antiproteases (allowing unopposed protease activity) |
|
|
how does nitric oxide elicit its effects?
|
paracrine hormone
induces cyclic guanosine monophosphate |
|
|
what are the three different types of nitric oxide synthase?
|
endothelial (eNOS)
neuronal (nNOS) inducible (iNOS) |
|
|
when is eNOS expressed?
|
constitutively at low levels and can be rapidly activated by increase in cytoplasmic calcium
|
|
|
when is nNOS expressed?
|
constitutively at low levels and can be rapidly activated by increase in cytoplasmic calcium
|
|
|
how is eNOS activated?
|
increased cytoplasmic calcium
|
|
|
how is nNOS activated?
|
increased cytoplasmic calcium
|
|
|
when is iNOS expressed?
|
induced when macrophages and other cells are activated by cytokines (TNF, IFN-gamma) or microbial products
|
|
|
what are the dual inflammatory actions of nitric oxide?
|
relaxes vascular smooth muscle and promotes vasodilation
inhibits cellular component of inflammatory response (reduces platelet aggregation and adhesion, inhibits leukocyte recruitment, inhibits mast cell-induced inflammation) |
|
|
by what cells is TNF mainly produced?
|
activated macrophages
|
|
|
by what cells is IL-1 mainly produced?
|
activated macrophages
|
|
|
what are the actions of TNF on endothelium?
|
induce expression of endothelial adhesion molecules
induce synthesis of chemical mediators (cytokines, chemokines, growth factors, eicosanoids, NO) increases surface thrombogenicity of endothelium |
|
|
what are the important cytokines in acute inflammation?
|
TNF
IL-1 IL-6 chemokines |
|
|
what are the important cytokines in chronic inflammation?
|
IL-12
IFN-gamma IL-17 |
|
|
what are the principal sources of TNF?
|
macrophages
mast cells T lymphocytes |
|
|
what are the principal sources of IL-1?
|
macrophages
endothelial cells some epithelial cells |
|
|
what are the principal sources of IL-6?
|
macrophages
|
|
|
what are the principal sources of chemokines?
|
macrophages
endothelial cells T lymphocytes mast cells |
|
|
what are the principal sources of IL-12?
|
dendritic cells
macrophages |
|
|
what are the principal sources of IFN-gamma?
|
T lymphocytes
NK cells |
|
|
what are the principal sources of IL-17?
|
T lymphocytes
|
|
|
what are the principal actions of TNF in inflammation?
|
stimulates expression of endothelial adhesion molecules
stimulates secretion of other cytokines systemic effects |
|
|
what are the principal actions of IL-1 in inflammation?
|
stimulates expression of endothelial adhesion molecules
stimulates secretion of other cytokines systemic effects (greater role in fever than TNF) |
|
|
what are the principal actions of IL-6 in inflammation?
|
systemic effects (acute-phase response)
|
|
|
what are the principal actions of chemokines in inflammation?
|
recruitment of leukocytes to sites of inflammation
migration of cells to normal tissues |
|
|
what are the principal actions of IL-12 in inflammation?
|
increased production of IFN-gamma
|
|
|
what are the principal actions of IFN-gamma in inflammation?
|
activation of macrophages
(increased ability to kill microbes and tumor cells) |
|
|
what are the principal actions of IL-17 in inflammation?
|
recruitment of neutrophils and monocytes
|
|
|
what is amyloidosis?
|
a disease of protein deposition that is often the result of persistent inflammation
|
|
|
how does TNF contribute to cancer cachexia?
|
regulates energy balance by promoting lipid and protein mobilization and by suppressing appetite
|
|
|
what are alpha chemokines?
|
aka C-X-C chemokines
have one amino acid residues separating the first two conserved cysteine residues |
|
|
on what cell type do alpha chemokines primarily work?
|
neutrophils
|
|
|
what is a typical alpha chemokine?
|
IL-8
secreted by macrophages and endothelial cells activates and chemoattracts neutrophils limited activity on monocytes and eosinophils |
|
|
by what cells is IL-8 secreted?
|
secreted by macrophages and endothelial cells
|
|
|
what are the effects of IL-8?
|
activates and chemoattracts neutrophils
limited activity on monocytes and eosinophils |
|
|
what are the most important inducers of IL-8?
|
IL-1
TNF |
|
|
what are beta chemokines?
|
aka C-C chemokines
first two conserved cysteine residues adjacent attract monocytes, eosinophils, basophils, and lymphocytes, but NOT neutrophils |
|
|
what types of cells do beta chemokines attract?
|
monocytes
eosinophils basophils lymphocytes NOT neutrophils |
|
|
what are the C-C chemokines?
|
monocyte chemoattractant protein (MCP-1)
eotaxin macrophage inflammatory protein-1alpha (MIP-1alpha) RANTES (regulated and normal T-cell expressed and secreted) |
|
|
what types of cells are recruited by eotaxin?
|
selectively eosinophils
|
|
|
what are gamma chemokines?
|
aka C chemokines
lack the first and third of the four conserved cysteines relatively specific for lymphocytes |
|
|
what cells are attracted by gamma chemokines?
|
relatively specific for lymphocytes
|
|
|
give an example of the gamma chemokines
|
lymphotactin
|
|
|
what are CX3C chemokines?
|
contain three amino acids between the two cysteines
fractalkine |
|
|
what is the only known CX3C chemokine?
|
fractalkine
|
|
|
what receptors act as coreceptors for a viral envelope glycoprotein of HIV and are involved in binding and entry of the virus into cells?
|
CXCR-4
CCR-5 |
|
|
what are the two main types of granules in neutrophils?
|
specific granules (secondary granules)
azurophil granules (primary granules) |
|
|
what is contained in specific (secondary granules) of neutrophils?
|
lysozyme
collagenase gelatinase lactoferrin plasminogen activator histaminase alkaline phosphatase |
|
|
what is contained in azurophil (primary granules) of neutrophils?
|
myeloperoxidase
lysozyme defensins acid hydrolases elastase cathepsin G nonspecific collagenases proteinase 3 |
|
|
what is the function of acid proteases?
|
degrade bacteria and debris within phagolysosomes, which easily reach acid pH
|
|
|
what is the function of neutral proteases?
|
degrading various extracellular components (collagen, basement membrane, fibrin, elastin, cartilage)
can cleave C3 and C5 complement proteins directly |
|
|
what enxymes hold the destructive effects of lysosomal enzymes in check?
|
antiproteases in the serum and tissue fluids
|
|
|
what is the most important antiprotease?
|
alpha1-antitrypsin
major inhibitor of neutrophil elastase |
|
|
what is the major inhibitor of neutrophil elastase?
|
alpha1-antitrypsin
|
|
|
what is the function of alpha1-antitrypsin?
|
inhibits neutrophil elastase
antiprotease that holds destructive effects of lysosomal enzymes in check |
|
|
what is the function of alpha2-macroglobulin?
|
antiprotease that holds destructive effects of lysosomal enzymes in check
|
|
|
to what family does substance P belong?
|
tachykinin neuropeptides
|
|
|
to what family does neurokinin A belong?
|
tachykinin neuropeptides
|
|
|
where are nerve fibers containing substance P prominent?
|
lung
gastrointestinal tract |
|
|
what are the functions of substance P?
|
- transmission of pain signals
- regulation of blood pressure - stimulation of secretion by endocrine cells - increase vascular permeability |
|
|
what is the critical step in complement activation?
|
proteolysis of component C3
|
|
|
what is the most abundant complement component in circulation?
|
C3
|
|
|
what are the three pathways by which C3 can be cleaved?
|
classical pathway
alternative pathway lectin pathway |
|
|
what is C3 convertase?
|
active enzyme formed in the early steps of complement activation, which splits C3 into C3a and C3b
|
|
|
which fragment of C3 binds to the cell or molecule where complement is being activated?
|
C3b
|
|
|
what is C5 convertase?
|
enzyme formed in the late stages of complement by the binding of C3b fragments to the C3 convertase; it is responsible for cleaving C5 to C5a and C5b
|
|
|
what complement component binds to the late complement components?
|
C5
binds C6, C7, C8, and C9 culminating in the formation of the membrane attack complex |
|
|
what complement component forms the pore in the membrane attack complex?
|
multiple C9 molecules
|
|
|
what are anaphylatoxins?
|
molecules that have effects similar to those of mast cell mediators in anaphylaxis
increase vascular permeability cause vasodilation |
|
|
to what types of cells is C5a a chemotactic agent?
|
neutrophils
monocytes eosinophils basophils |
|
|
what arachidonic acid pathway is activated by C5a?
|
lipoxygenase pathway
|
|
|
what proteolytic enzymes within the inflammatory exudate can cleave C3 and C5?
|
plasmin
neutrophil lysosomal enzymes (neutral proteases) |
|
|
by what protein is the intrinsic clotting pathway activated?
|
Hageman factor (factor XII)
|
|
|
what activates factor XII (Hageman factor)?
|
contact with negatively charged surfaces
|
|
|
what are PARs?
|
protease-activated receptors
bind multiple trypsin-like serine proteases in addition to thrombin, and as a result induce inflammation |
|
|
what ttriggers type 1 PAR to induce inflammation?
|
engagement by proteases, particularly thrombin
|
|
|
what are the responses of cells to PAR-1 activation by thrombin?
|
- mobilization of P-selectin
- production of chemokines and other cytokines - expression of endothelial adhesion molecules for leukocyte integrins - induction of COX-2 and production of prostaglandins - production of PAF and NO - changes in endothelial shape |
|
|
what are kinins?
|
vasoactive peptides derived from plasma proteins, called kininogens, by the action of specific proteases called kallikreins
|
|
|
what enzyme converts plasma prekallikrein into kallikrein?
|
active form of factor XII (XIIa)
|
|
|
what is the function of kallikrein?
|
cleave high-molecular-weight kininogen into bradykinin
|
|
|
what enzyme cleaves high-molecular-weight kininogen into bradykinin?
|
kallikrein
|
|
|
from what plasma protein is the active enzyme kallikrein converted?
|
prekallikrein
|
|
|
from what plasma glycopotein precursor is bradykinin derived?
|
high-molecular-weight kininogen
|
|
|
what are the effects of bradykinin when it is injected into the skin?
|
increased vascular permeability
contraction of smooth muscle dilation of blood vessels pain |
|
|
why are the actions of bradykinin short-lived?
|
bradykinin is quickly inactivated by kininase
|
|
|
what enzyme quickly inactivates bradykinin?
|
kininase
|
|
|
what enzyme inactivates kinins which are not inactivated by kininase?
|
angiotensin-converting enzyme (ACE)
|
|
|
where is angiotensin-converting enzyme located?
|
lung
|
|
|
what two enzymes inactivate kinins?
|
kininase (quick)
angiotensin-converting enzyme (slower) |
|
|
how can the initial stimulus of the coagulation system be autocatalytically amplified?
|
kallikrein (formed from prekallikrein by factor XIIa) is a potent activator of Hageman factor (factor XIIa)
|
|
|
what enzymes can cleave plasminogen?
|
kallikrein
plasminogen activator |
|
|
from where is plasminogen activator released?
|
endothelium
leukocytes |
|
|
what is plasminogen?
|
plasma protein that binds to an evolving fibrin clot to generate plasmin
|
|
|
what is plasmin?
|
a multifunctional protease that lyses fibrin clots, cleaves C3, and degrades fibrin to form fibrin split products
|
|
|
what are the most important mediators of increased vascular permeability in the complement, kinin, and clotting cascades?
|
bradykinin
C3a C5a |
|
|
what is the most important mediator of chemotaxis in the complement, kinin and clotting cascades?
|
C5a
|
|
|
what is the most important effector on endothelial cells and other cell types in the complement, kinin, and clotting cascades?
|
thrombin
|
|
|
what is the primary function of plasmin?
|
lyse fibrin clots
|
|
|
what are the ways C3a and C5a can be generated?
|
1) immunologic reactions, involving antibodies and complement
2) activation of the alternative and lectin complement pathways 3) plasmin, kallikrein, serine proteases |
|
|
what four systems involved in the inflammatory response are initiated by activated Hageman factor?
|
1) kinin system (produces vasoactive kinins)
2) clotting system (induces formation of thrombin) 3) fibrinolytic system (produces plasmin and degrades fibrin) 4) complement system (opsonizes and produces anaphylatoxins) |
|
|
what are the mediators for vasodilation in inflammation?
|
prostaglandins
nitric oxide histamine |
|
|
what are the mediators for increased vascular permeability in inflammation?
|
histamine and serotonin
C3a and C5a (indirectly) bradykinin leukotrienes C4, D4, E4 PAF substance P |
|
|
what are the mediators for chemotaxis, leukocyte recruitment and leukocyte activation in inflammation?
|
TNF, IL-1
chemokines C3a, C5a LTB4 |
|
|
what are the mediators for fever in inflammation?
|
IL-1, TNF
prostaglandins |
|
|
what are the mediators for pain in inflammation?
|
prostaglandins
bradykinin |
|
|
what are the mediators for tissue damage in inflammation?
|
lysosomal enzymes of leukocytes
reactive oxygen species nitric oxide |
|
|
what are the three possible outcomes for acute inflammation?
|
1) complete resolution
2) healing by connective tissue replacement 3) progression to chronic inflammation |
|
|
what is considered complete resolution of acute inflammation?
|
restoration of the site of acute inflammation to normal
|
|
|
when might resolution occur in acute inflammation?
|
if the injury is limited or short-lived or when there has been little tissue damage
|
|
|
what is fibrosis?
|
healing by connective tissue replacement
|
|
|
when would you see fibrosis as the result of acute inflammation?
|
after substantial tissue destruction, when the inflammatory injury involves tissues that are incapable of regeneration, or when there is abundant fibrin exudation in tissue or serous cavities that cannot adequately be cleared
|
|
|
what is the process called organization in acute inflammation?
|
connective tissue grows into an area of damage or exudate, converting it into a mass of fibrous tissue
|
|
|
what are the morphologic hallmarks of acute inflammatory reactions?
|
- dilation of small blood vessels
- slowing of blood flow - accumulation of leukocytes and fluid in the extravascular tissue |
|
|
what is serous inflammation?
|
outpouring of a thin fluid that may be derived from the plasma or from the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities
|
|
|
what is an effusion?
|
accumulation of fluid in peritoneal, pleural, or pericardial cavities
|
|
|
what does the skin blister resulting from a burn or viral infection represent?
|
large accumulation of serous fluid, either within or immediately beneath the epidermis
|
|
|
when does a fibrinous exudate develop?
|
when vascular leaks are large or there is a local procoagulant stimulus
|
|
|
fibrinous exudate is characteristic of inflammation where?
|
the lining of body cavities
meninges pericardium pleura |
|
|
how does fibrin appear histologically?
|
eosinophilic meshwork of threads or sometimes an amorphous coagulum
|
|
|
how can fibrinous exudates be removed?
|
fibrinolysis and clearing of other debris by macrophages
|
|
|
what is the result of conversion of fibrinous exudate to scar tissue within the pericardial sac?
|
leads to opaque fibrous thickening of the pericardium and epicardium in the area of exudation and, if the fibrosis is extensive, obliteration of the pericardial space
|
|
|
what are the four morphologic patterns of acute inflammation?
|
serous inflammation
fibrinous inflammation suppurative or purulent inflammation; abscess ulcers |
|
|
what is suppurative inflammation characterized by?
|
production of large amounts of pus or purulent exudate consisting of neutrophils, liquefactive necrosis, and edema fluid
|
|
|
what are pyogenic bacteria?
|
pus-producing bacteria
those that produce localized suppuration (e.g. staphylococci) |
|
|
what are abscesses?
|
localized collections of purulent inflammatory tissues caused by suppuration buried in a tissue, an organ, or a confined space
|
|
|
how are abscesses produced?
|
deep seeding of pyogenic bacteria into a tissue
|
|
|
describe abscesses
|
central region that appears as a mass of necrotic leukocytes and tissue cells
zone of preserved neutrophils around the necrotic focus vascular dilation and parenchymal and fibroblastic proliferation occur outside the necrotic focus |
|
|
what is an ulcer?
|
a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue
|
|
|
summarize the sequence of events in a typical acute inflammation scenario
|
injurious agent -> resident phagocytes try to eliminate agent -> phagocytes & other cells release inflammatory mediators -> mediators act on blood vessels and circulating leukocytes -> leukocytes come to location of offending agent -> leukocytes activated by injurious agent -> leukocytes try to remove offending agent by phagocytosis -> process subsideswhen agent is removed
|
|
|
what is chronic inflammation?
|
inflammation of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in varying combinations
|
|
|
what type of immune reaction is evoked by persistent infections by microorganisms?
|
delayed-type hypersensitivity reactions
sometimes takes a specific pattern called granulomatous reaction |
|
|
what are the morphological features that characterize chronic inflammation?
|
infiltration with nononuclear cells (macrophages, lymphocytes, plasma cells)
tissue destruction attempts at healing by connective tissue replacement of damaged tissue |
|
|
what is the dominant cellular player in chronic inflammation?
|
macrophage
|
|
|
what is the reticuloendothelial system?
|
mononuclear phagocyte system
consists of closely related cells of bone marow origin, including blood monocytes and tissue macrophages |
|
|
where are tissue macrophages found?
|
diffusely scattered in the connective tissue or located in organs such as liver (Kupffer cells), spleen and lymph nodes (sinus histiocytes), lungs (alveolar macrophages) , and central nervous system (microglia)
|
|
|
what is another name for liver macrophages?
|
Kupffer cells
|
|
|
what is another name for macrophages of the spleen and lymph nodes?
|
sinus histiocytes
|
|
|
what is another name for lung macrophages?
|
alveolar macrophages
|
|
|
what is another name for central nervous system macrophages?
|
microglia
|
|
|
what is the common precursor for macrophages?
|
blood monocytes
|
|
|
what is the half-life of a blood monocyte? how does that compare to the life span of a tissue macrophage?
|
blood monocyte - about one day
tissue macrophges - several months or years |
|
|
when do monocytes constitiute the predominant cell type in inflamation?
|
within 48 hours
|
|
|
by what stimuli are macrophages activated?
|
microbial products
cytokines (IFN-gamma) |
|
|
what is the result of activation of macrophages?
|
increased levels of lysosomal enzymes and reactive oxygen and nitrogn species and production of cytokines, growth factors, and other inflammatory mediators
|
|
|
how does macrophage population differ between short-lived and chronic inflammation?
|
short-lived - disappear when irritant is eliminated
chronic - macrophage accumulation persists |
|
|
what causes macrophage accumulation to persist in chronic inflammation?
|
continuous recruitment from circulation
local proliferation at the site of inflammation |
|
|
what cell types are involved in chronic inflammation?
|
macrophages
lymphocytes plasma cells eosinophils mast cells |
|
|
what cytokines promote lymphocyte recruitment?
|
TNF
IL-1 chemokines |
|
|
in what situations are eosinophils important?
|
immune reactions mediated by IgE
parasitic infections |
|
|
what chemokine is especially important for eosinophil recruitment?
|
eotaxin
|
|
|
what is major basic protein?
|
highly cationic protein that is toxic to parasites
also causes lysis of mammalian cells |
|
|
what receptor is expressed on the surface of mast cells that binds the Fc portion of IgE?
|
FcepsilonRI
|
|
|
on what cells is FcepsilonRI found?
what does it bind? |
mast cells
Fc portion of IgE antibody |
|
|
what happens in immediate hypersensitivity reactions?
|
IgE antibodies bound to mast cells' FcepsilonRI receptors specifically recognize antigen, the cells degranulate and release mediators (histamine and prostaglandins)
|
|
|
what is seen prominently in chronic inflammatory reactions?
|
cellular infiltrates
growth of blood vessels growth of lymphatic vessels |
|
|
what growth factor stimulates the growth of blood vessels and lymphatic vessels in inflammation?
|
vascular endothelial growth factor (VEGF)
|
|
|
what cells produce VEGF?
|
macrophages
endothelial cells |
|
|
what is a granuloma?
|
a cellular attempt to contain an offending agent that is difficult to eradicate
focus of chronic inflammation consisting of a microscopic aggregation of macrophages that are transformed into epithelium-like cells, surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells |
|
|
how do granulomas appear in H&E-stained tissue sections?
|
epitheloid cells have a pale pink granular cytoplasm with indistinct cell boundaries, often appearing to merge into one another
|
|
|
what develops in older granulomas?
|
enclosing rim of fibroblasts and connective tissue
|
|
|
what are giant cells in granulomas?
|
large cells formed from the fusion of multiple epitheloid cells in the periphery or in the center of granulomas
|
|
|
what are the two types of granulomas?
|
foreign body granulomas
immune granulomas |
|
|
what is the pathogenesis of foreign body granulomas?
|
relatively inert foreign bodies incite granuloma formation around them
usually large fibers or molecules that are too big to be phagocytosed by a single macrophage and don't activate any specific inflammatory/immune response |
|
|
what is the pathogenesis of immune granulomas?
|
macrophages engulf poorly degradable protein antigens, process it, and present peptides to antigen specific T cells causing their activation, which then perpetuate the response and secrete IFN-gamma which is important in transforming the macrophage into an epitheloid cell
|
|
|
what is acute-phase response?
|
collection of systemic changes associated with acute inflammation
|
|
|
what are pyrogens?
|
substances that induce fever
act by stimulating prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus |
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how do pyrogens effect a body temperature elevation of 1-4 degrees celcius?
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stimulate prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus
prostaglandins, esp. PGE2, stimulated production of NTs like cAMP which function to reset/elevate the temperature set point |
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what are the two types of pyrogens?
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endogenous (IL-1 and TNF)
exogenous (LPS) |
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how do NSAIDs reduce fever?
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inhibit prostaglandin synthesis
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where are acute phase proteins synthesized?
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liver
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what are the three best-known acute-phase proteins?
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C-reactive protein
fibrinogen serum amyloid A |
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what chemical mediators upregulate the synthesis of acute-phase proteins by hepatocytes?
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IL-6 (CRP and fibrinogen)
IL-1 (serum amyloid A/SAA) TNF (serum amyloid A/SAA) |
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what is the effect of CRP and SAA on microbes?
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bind to microbial cell walls and act as opsonins (fix complement)
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how do acute phase proteins help clear necrotic cell nuclei?
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bind chromatin, opsonizing it
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why does serum amyloid A replace apolipoprotein A in HDL particles?
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allows HDL particles to be targeted by macrophages, which can use them as a source of energy-producing lipids
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what replaces apolipoprotein A in HDL particles during the acute-phase response?
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serum amyloid A (SAA), an acute-phase protein
allows HDL particles to be targeted by macrophages, which can use them as a source of energy-producing lipids |
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what is the basis for measuring the erythrocyte sedimentation rate?
|
during the acute-phase response, fibrinogen (an acute-phase protein) binds to red cells and causes them to form stacks (rouleaux) that sediment more rapidly at unit gravity than do individual red cells
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what are rouleaux?
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stacks of red blood cells formed by their binding to fibrinogen
causes them to sediment more rapidly than individual red cells at unit gravity |
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what is caused by prolonged production of acute-phase proteins?
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secondary amyloidosis
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what is the cause of anemia associated with chronic inflammation?
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the production of the iron-regulating peptide, hepcidin, is increased during the acute-phase response
chronically elevated plasma concentrations of hepcidin reduce the availability of iron and are therefore responsible for the anemia |
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what is leukocytosis?
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elevated number of leukocytes in the blood
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how high do leukocyte counts usually climb in inflammatory reactions?
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15,000-20,000 cell/uL
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at what serum leukocyte levels is a person considered to have a leukemoid reaction?
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40,000-100,000 cells/uL
these are similar white cell counts to those observed in leukemia |
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what is the initial cause of leukocytosis?
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accelerated release of cells from the bone marrow postmitotic reserve pool
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with what is leukocytosis associated?
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rise in the number of more immature neutrophils in the blood (shift to the left)
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what is the effect in the bone marrow of polonged infection?
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proliferation of precursors caused by increased production of colony-stimulating factors
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what is neutrophilia?
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increase in the blood neutrophil count
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what is lymphocytosis?
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absolute increase in the number of lymphocytes
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what is eosinophilia?
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increase in the absolute number of eosinophils
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what is leukopenia?
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decreased number of circulating white cells
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what are the manifestations of the acute phase response?
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increased pulse
increased b.p. decreased sweating rigors (shivering) chills (search for warmth) anorexia somnolence malaise |
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why does the acute-phase response cause a decrease in sweating?
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mainly because of redirection of blood flow from cutaneous to deep vascular beds to minimize heat loss through the skin
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what is sepsis?
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severe illness in which the bloodstream is overwhelmed by bacteria
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what cytokines are produced in enormous quantities in sepsis? what stimulates this overproduction?
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TNF and IL-1
LPS in the blood |
