Inflammation 1 Flashcards
Inflammation is a response of _________ to ______ and ______ tissues that bring cells and molecules of _______ from the _______ to the sites where they are needed, in order to eliminate the offending agents.
vascularized tissues
infections
damaged
host defense
Circulation
The process of inflammation delivers __________ and proteins (_______ and ______) to damaged or necrotic tissues and foreign invaders, such as microbes,
Then activates recruited cells and molecules, which then function to get rid of the harmful or unwanted substances.
phagocytic leukocytes
antibodies and complement proteins
Without inflammation, infections would go _______, wounds would ______, and injured tissues might remain __________
unchecked
never heal
permanent festering sores.
The components of innate immunity which include ______ cells, _____ cells, and _______ cells, as well as (soluble or insoluble?) factors such as the proteins of the complement system provide first response to infection apart from leukocytes.
natural killer
dendritic
epithelial
Insoluble
The typical inflammatory reaction develops through a series of sequential steps:
• The offending agent, which is located in (intra or extra?) vascular tissues, is ________
•________ and ____ are recruited from the circulation to the site where the offending agent is located.
• The _______ are ______; together they destroy and eliminate the offending substance.
The damaged tissue is _____.
Extra; recognized by host cells and molecules.
Leukocytes and plasma proteins
leukocytes and proteins ; activated
repaired
Inflammation reaction is controlled and terminated at a point
T/F
T
Mention the cells and molecule involved in the injury
Acute respiratory distress syndrome
Neutrophils
Mention the cells and molecule involved in the injury
Acute asthma
Eosinophils
Ig E antibodies
Mention the cells and molecule involved in the injury
Glomerulonephritis
Antibodies
Complement proteins
Neutrophils
Monocytes
Mention the cells and molecule involved in the injury
Septic shock
Cytokines
Mention the cells and molecule involved in the injury
Chronic arthritis
Lymphocytes
Macrophages
Antibodies
Mention the cells and molecule involved in the injury
Chronic asthma
Eosinophils
Ig E antibodies
Mention the cells and molecule involved in the injury
Atherosclerosis
Macrophages
Lymphocytes
Mention the cells and molecule involved in the injury
Pulmonary fibrosis
Macrophages
Fibroblasts
Acute inflammation.
• The initial, (slow or rapid?) response to infections and tissue damage.
• It typically develops within ______ or _____ and is of (short or long?) duration, lasting for ________ or _______;
Rapid
minutes or hours; short; several hours or a few days
Acute inflammation
Its main characteristics are the ________ and ______ and the emigration of ______, predominantly _______
exudation of fluid and plasma proteins (edema)
leukocytes
neutrophils
neutrophils also called ______ leukocytes
polymorphonuclear
Chronic inflammation.
• It is of (shorter or longer?) duration, (slow or rapid ?) in onset
Longer; slow
Chronic inflammation.
It is associated with –
• more _______
• the presence of ___________
• proliferation of _______, and the deposition of _________
tissue destruction
lymphocytes and macrophages
blood vessels; connective tissue
Cardinal signs of inflammation
•______ (______),
• ______ (_____),
• _____ (_____),
• _____ (_____).
• _____(_________)
rubor; redness
Tumor; swelling
Calor; heat
Dolor; pain
Function laesa; loss of function
Causes of Inflammation:
• ______
• Tissue ________
• _______
• Deposition of ______- substances
•———- reactions (also called _______)
Infections
necrosis - ischemia
Foreign bodies
endogenous
Immune; hypersensitivity
Causes of Inflammation:
• Deposition of endogenous substances – harmful when (small or large?) amounts are deposited in tissues; such substances include _____ (in the disease gout), _______ (in atherosclerosis), and _____ (in obesity-associated metabolic syndrome).
Large
urate crystals; cholesterol crystals; lipids
Causes of Inflammation:
• Immune reactions - The injurious immune responses may be directed against ________, causing _______, or may be inappropriate reactions against environmental substances, as in _______, or against microbes.
self antigens ; autoimmune diseases
allergies
ACUTE INFLAMMATION
Acute inflammation has three major components:
_________ leading to __________
increased ______of the microvasculature enabling _____ and ________ to leave the circulation, and
___________ from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
dilation of small vessels; an increase in blood flow
permeability ; plasma proteins and leukocytes
emigration of the leukocytes
Reactions of Blood Vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of
-changes in the _______ and
-the _______ of vessels,
both of the above is designed to maximize the movement of _____ and ______ out of the circulation and into the site of infection or injury.
flow of blood
permeability
plasma proteins and leukocytes
The escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities is known as _________
exudation
An exudate is an _____vascular fluid that has a high _____ concentration and contains _______
extra
protein
cellular debris.
a transudate is a fluid with (high or low?) protein content (most of which is _______), ______ cellular material, and ( low or high?) specific gravity.
Low
albumin
little or no
Low
Transudate is essentially an ultrafiltrate of blood plasma that is produced as a result of _____ or _____ imbalance across the vessel wall without ______
osmotic or hydrostatic
an increase in vascular permeability.
Edema is exudate
T/F
F
it can be either an exudate or a transudate.
Pus, a purulent (exudate or transudate?) , is an inflammatory _____, rich in ______ (mostly _____), the debris of dead cells and, in many cases, microbes
exudate; exudate
leukocytes; neutrophils
• Changes in vascular flow and caliber begin early after injury
• It consist of the following:
I. Vaso______ induced by the action of several mediators, notably ______, on vascular smooth muscle.
• It first involves the _____ and then leads to _________ in the area.
• The result is _______, which is the cause of ______ and _____ at the site of inflammation.
dilation; histamine
arterioles; opening of new capillary beds
increased blood flow
heat and redness
one of the earliest manifestations of acute inflammation is ???
Vasodilation
Changes in vascular flow and caliber begin early after injury
• It consist of the following:
II. Vasodilation is quickly followed by _________ of the microvasculature
• There is outpouring of ____-rich fluid into the _____vascular tissues.
increased permeability
protein
Extra
In acute inflammation, The loss of fluid and increased vessel diameter lead to _____ blood flow, concentration of red cells in small vessels, and increased ______ of the blood.
• These changes result in engorgement of small vessels with _____ moving red cells, a condition termed ______, which is seen as ________ and localized _____ of the involved tissue.
slower
viscosity; slowly; stasis
vascular congestion ; redness
• As stasis develops, blood _____, principally _____, accumulate along the vascular endothelium.
• Also endothelial cells are activated by mediators produced at _________
• The endothelial cells express increased levels of ________
• ______ then adhere to the endothelium, and soon afterward they migrate through the _______ into the interstitial tissue.
leukocytes; neutrophils
sites of infection and tissue damage
adhesion molecules.
Leukocytes; vascular wall
Increased Vascular Permeability (Vascular Leakage)
• Several mechanisms are responsible for the increased permeability of postcapillary venules, a hallmark of _____ inflammation
acute
Increased Vascular Permeability (Vascular Leakage)
a. (Contraction or dilatation?) of endothelial cells resulting in increased __________ is the most common mechanism of vascular leakage.
• It is elicited by _____,______,_______, and other chemical mediators.
• It is called the ______ response because it occurs (slowly or rapidly?) after exposure to the mediator and is usually (short or long?)- lived (______).
Contraction
inter- endothelial spaces
histamine, bradykinin, leukotrienes
immediate transient
Rapidly; short; 15-30 minutes
In some forms of mild injury (e.g., after burns, irradiation or ultraviolet radiation, and exposure to certain bacterial toxins), vascular leakage begins after a delay of ____________ and lasts for _______
2 to 12 hours
several hours or even days;
This delayed and prolonged vascular leakage may be caused by ____________ or ___________
___________ is a good example of this type of leakage.
contraction of endothelial cells or mild endothelial damage.
Late-appearing sunburns
Several mechanisms are responsible for the increased permeability of postcapillary venules
_________, resulting in _________ and detachment
•____ damage to the endothelium is encountered in severe injuries, for example, in burns, or is induced by the actions of microbes and microbial toxins that target endothelial cells.
• _____ that adhere to the endothelium during inflammation may also injure the endothelial cells and thus amplify the reaction.
• In most instances leakage starts ____ after injury and is sustained for _______ until the damaged vessels are thrombosed or repaired.
Endothelial injury
endothelial cell necrosis; Direct
Neutrophils
immediately; several hoursm
Neutrophils that adhere to the endothelium during inflammation may also injure the endothelial cells
T/F
T
Several mechanisms are responsible for the increased permeability of postcapillary venules
Increased transport of fluids and proteins, called _________, through the endothelial cell.
•This process may involve intracellular channels that may be stimulated by certain factors, such as _________
transcytosis
vascular endothelial growth factor (VEGF).
Responses of Lymphatic Vessels and Lymph Nodes
• Lymph flow is ___eased and helps drain _____
• Also ______ and ______ , as well as _____, may find their way into lymph.
• Lymphatic vessels, like blood vessels, _______ during inflammatory reactions to __________
Incr; edema fluid
leukocytes and cell debris; microbes
proliferate; handle the increased load.
Responses of Lymphatic Vessels and Lymph Nodes
• The lymphatics may become secondarily inflamed (_______), as may the draining lymph nodes ( _______ ).
• Inflamed lymph nodes are often ____- due to ______ of the lymphoid follicles.
• This constellation of pathologic changes is termed —, or inflammatory lymphadenitis
lymphangitis: lymphadenitis
Enlarged; hyperplasia
reactive
Leukocyte Recruitment to Sites of Inflammation
• The changes in _____ and ______ are quickly followed by an influx of leukocytes into the tissue.
• These leukocytes perform the key function of ___________
• The most important leukocytes are the ones capable of ————-, namely _______ and ______
• These leukocytes _____ and destroy bacteria and other microbes, as well as necrotic tissue and foreign substances.
• Leukocytes also produce _____ that aid in repair.
blood flow and vascular permeability
eliminating the offending agents.
phagocytosis; neutrophils and macrophages.
ingest
growth factors; repair
The journey of leukocytes from the vessel lumen to the tissue is a multistep process
It is mediated and controlled by _______ molecules and ______ called _______.
• This process can be divided into sequential phases:
I. In the lumen: _____,_____, and ____ to endothelium.
II. Migration ___________
III. Migration in the _____ toward a ______
adhesion; cytokines; chemokines
margination, rolling, and adhesion
across the endothelium and vessel wall
tissues; chemotactic stimulus
The journey of leukocytes from the vessel lumen to the tissue is a multistep process
• This process can be divided into sequential phases:
I. In the lumen: margination, rolling, and adhesion to endothelium.
Vascular endothelium normally does not __________ or _______
In inflammation, the endothelium is ________ and can bind leukocytes as a prelude to their exit from the blood vessels.
bind circulating cells or impede their passage.
activated
Leukocyte Adhesion to Endothelium
• In normally flowing blood in venules, red cells are confined to a __________, displacing the leukocytes toward the ____ of the vessel.
• Due to slow blood flow (_____) and hemodynamic conditions change (wall _____ ____eases), more white cells assume a peripheral position along the endothelial surface.
• This process of leukocyte redistribution is called ______.
• Subsequently, leukocytes adhere ______ to the endothelium,____ and ______ again, thus ______ on the vessel wall.
• The cells finally come to rest where they adhere (weakly or firmly?) (resembling pebbles over which a stream runs without disturbing them).
• The attachment of leukocytes to endothelial cells is mediated by _________ molecules on the two cell types whose expression is enhanced by cytokines.
central axial column; wall
stasis; shear stress decr
margination; transiently ; detach and bind
rolling; firmly
complementary adhesion
Cytokines are secreted by _____ cells in tissues in response to microbes and other injurious agents.
• This ensures that ______ are recruited to the tissues where these stimuli are present.
sentinel; leukocytes
The two major families of molecules involved in leukocyte adhesion and migration are the ______ and ____, and their ligands.
They are expressed on ______ and _______ cells.
selectins and integrins
leukocytes and endothelial
Leukocytes adhesion to endothelia cells
The initial rolling interactions are mediated by a family of proteins called
_______.
selectins
There are three types of selectins:
•__-selectin – expressed on ______,
• __-selectin – expressed on ______
• __-selectin - expressed on _____________
L; leukocytes
E; endothelium
P; platelets and on endothelium
The ligands for selectins are __________ bound to _____- like ______ backbones.
sialylated oligosaccharides
mucin; glycoprotein
The expression of selectins and their ligands is regulated by _______ produced in response to infection and injury.
cytokines
Tissue macrophages, mast cells, and endothelial cells that encounter microbes and dead tissues respond by secreting several _____, including ________,____ and ______
cytokines
tumor necrosis factor (TNF)
IL-1, chemokines (chemoattractant cytokines).
TNF and IL-1 act on the _____ cells of postcapillary venules adjacent to the infection and induce the _______ of numerous adhesion molecules.
• Within _______ hours the endothelial cells begin to expres ___-selectin and the ____ for __-selectin.
• Other mediators such as ____ and ______, stimulate the redistribution of __-selectin from its normal ___cellular stores in _____ cell granules to the cell surface.
endothelial; coordinate expression
1 to 2 ; E; ligands; L
histamine and thrombin
P; intra; endothelial
P-selectin intracellular stores is called _______ bodies
Weibel-Palade
Leukocytes express ___-selectin at the ___ of their _____ and also express _____ for _______-selectins, all of which bind to the complementary molecules on the endothelial cells.
L; tips; micovilli
ligands; E- and P
Selectins are (low or high?) -affinity interactions with a (slow or fast?) off rate.
Low
Fast
These weak rolling interactions ____ the leukocytes.
slow down
Firm adhesion is mediated by a family of __________ leukocyte surface proteins called _______.
heterodimeric
integrins
___________ induce endothelial expression of ligands for integrins, mainly (______, the ligand for the β1 integrin VLA-4) and _____, the ligand for the β2 integrins LFA-1 and Mac-1).
TNF and IL-1
VCAM-1
ICAM-1
Full meaning of VCAM
Full meaning of ICAM
vascular cell adhesion molecule
intercellular adhesion molecule
Leukocytes normally express integrins in a (low or high?) affinity state.
Low
Chemokines that were produced at the site of injury bind to endothelial cell _____, and are displayed at (low or high?) concentrations on the endothelial surface.
proteoglycans; high
chemokines bound on the endothelial wall bind to and activate the rolling leukocytes.
T/F
T
One of the consequences of activation of leukocytes is the conversion of _____ and _______ on the leukocytes to a (low or high?) -affinity state.
VLA-4 and LFA-1 integrins
High
The combination of cytokine-induced expression of integrin ligands on the ______ and increased integrin affinity on the ______ results in firm integrin-mediated binding of the leukocytes to the endothelium at the site of inflammation.
endothelium
leukocytes
After firm adhesion by integrins, The leukocytes stop rolling, their ______ is reorganized, and they spread out on the ______
cytoskeleton
endothelial surface.
Leukocyte migration through endothelium
• The migration of the leukocytes through the endothelium is called _______ or ______
transmigration or diapedesis.
Transmigration of leukocytes occurs mainly in ________
postcapillary venules.
• Chemokines act on the ____ leukocytes and stimulate the cells to migrate through inter endothelial spaces toward the chemical concentration gradient.
• Several _________ present in the intercellular junctions between endothelial cells are involved in the migration of leukocytes.
• These molecules include a member of the _________ called __________________
adherent
adhesion molecules
immunoglobulin superfamily
CD31 or PECAM-1
Full meaning of PECAM
platelet endothelial cell adhesion molecule