Inflammation 1 Flashcards
1
Q
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.
A
vascularized tissues
infections
damaged
host defense
Circulation
2
Q
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.
A
phagocytic leukocytes
antibodies and complement proteins
3
Q
Without inflammation, infections would go _______, wounds would ______, and injured tissues might remain __________
A
unchecked
never heal
permanent festering sores.
4
Q
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.
A
natural killer
dendritic
epithelial
Insoluble
5
Q
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 _____.
A
Extra; recognized by host cells and molecules.
Leukocytes and plasma proteins
leukocytes and proteins ; activated
repaired
6
Q
Inflammation reaction is controlled and terminated at a point
T/F
A
T
7
Q
Mention the cells and molecule involved in the injury
Acute respiratory distress syndrome
A
Neutrophils
8
Q
Mention the cells and molecule involved in the injury
Acute asthma
A
Eosinophils
Ig E antibodies
9
Q
Mention the cells and molecule involved in the injury
Glomerulonephritis
A
Antibodies
Complement proteins
Neutrophils
Monocytes
10
Q
Mention the cells and molecule involved in the injury
Septic shock
A
Cytokines
11
Q
Mention the cells and molecule involved in the injury
Chronic arthritis
A
Lymphocytes
Macrophages
Antibodies
12
Q
Mention the cells and molecule involved in the injury
Chronic asthma
A
Eosinophils
Ig E antibodies
13
Q
Mention the cells and molecule involved in the injury
Atherosclerosis
A
Macrophages
Lymphocytes
14
Q
Mention the cells and molecule involved in the injury
Pulmonary fibrosis
A
Macrophages
Fibroblasts
15
Q
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 _______;
A
Rapid
minutes or hours; short; several hours or a few days
16
Q
Acute inflammation
Its main characteristics are the ________ and ______ and the emigration of ______, predominantly _______
A
exudation of fluid and plasma proteins (edema)
leukocytes
neutrophils
17
Q
neutrophils also called ______ leukocytes
A
polymorphonuclear
18
Q
Chronic inflammation.
• It is of (shorter or longer?) duration, (slow or rapid ?) in onset
A
Longer; slow
19
Q
Chronic inflammation.
It is associated with –
• more _______
• the presence of ___________
• proliferation of _______, and the deposition of _________
A
tissue destruction
lymphocytes and macrophages
blood vessels; connective tissue
20
Q
Cardinal signs of inflammation
•______ (______),
• ______ (_____),
• _____ (_____),
• _____ (_____).
• _____(_________)
A
rubor; redness
Tumor; swelling
Calor; heat
Dolor; pain
Function laesa; loss of function
21
Q
Causes of Inflammation:
• ______
• Tissue ________
• _______
• Deposition of ______- substances
•———- reactions (also called _______)
A
Infections
necrosis - ischemia
Foreign bodies
endogenous
Immune; hypersensitivity
22
Q
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).
A
Large
urate crystals; cholesterol crystals; lipids
23
Q
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.
A
self antigens ; autoimmune diseases
allergies
24
Q
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
A
dilation of small vessels; an increase in blood flow
permeability ; plasma proteins and leukocytes
emigration of the leukocytes
25
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
26
The escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities is known as _________
exudation
27
An exudate is an _____vascular fluid that has a high _____ concentration and contains _______
extra
protein
cellular debris.
28
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
29
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.
30
Edema is exudate
T/F
F
it can be either an exudate or a transudate.
31
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
32
• 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
33
one of the earliest manifestations of acute inflammation is ???
Vasodilation
34
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
35
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
36
• 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
37
Increased Vascular Permeability (Vascular Leakage)
• Several mechanisms are responsible for the increased permeability of postcapillary venules, a hallmark of _____ inflammation
acute
38
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
39
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;
40
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
41
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
42
Neutrophils that adhere to the endothelium during inflammation may also injure the endothelial cells
T/F
T
43
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).
44
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.
45
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
46
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
47
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
48
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
49
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
50
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
51
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
52
Leukocytes adhesion to endothelia cells
The initial rolling interactions are mediated by a family of proteins called
_______.
selectins
53
There are three types of selectins:
•__-selectin – expressed on ______,
• __-selectin – expressed on ______
• __-selectin - expressed on _____________
L; leukocytes
E; endothelium
P; platelets and on endothelium
54
The ligands for selectins are __________ bound to _____- like ______ backbones.
sialylated oligosaccharides
mucin; glycoprotein
55
The expression of selectins and their ligands is regulated by _______ produced in response to infection and injury.
cytokines
56
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).
57
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
58
P-selectin intracellular stores is called _______ bodies
Weibel-Palade
59
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
60
Selectins are (low or high?) -affinity interactions with a (slow or fast?) off rate.
Low
Fast
61
These weak rolling interactions ____ the leukocytes.
slow down
62
Firm adhesion is mediated by a family of __________ leukocyte surface proteins called _______.
heterodimeric
integrins
63
___________ 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
64
Full meaning of VCAM
Full meaning of ICAM
vascular cell adhesion molecule
intercellular adhesion molecule
65
Leukocytes normally express integrins in a (low or high?) affinity state.
Low
66
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
67
chemokines bound on the endothelial wall bind to and activate the rolling leukocytes.
T/F
T
68
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
69
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
70
After firm adhesion by integrins, The leukocytes stop rolling, their ______ is reorganized, and they spread out on the ______
cytoskeleton
endothelial surface.
71
Leukocyte migration through endothelium
• The migration of the leukocytes through the endothelium is called _______ or ______
transmigration or diapedesis.
72
Transmigration of leukocytes occurs mainly in ________
postcapillary venules.
73
• 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
74
Full meaning of PECAM
platelet endothelial cell adhesion molecule
75
After traversing the endothelium, leukocytes pierce the _______, probably by secreting ______, and enter the _______ tissue.
The cells then migrate toward the ______ created by ______ and other _____ and accumulate in the extravascular site.
basement membrane
collagenases; extravascular
chemotactic gradient; chemokines; chemoattractants
76
The most telling proof of the importance of leukocyte adhesion molecules is the existence of ________ in these molecules that result in recurrent bacterial infections
genetic deficiencies
77
Chemotaxis of Leukocytes
• Chemotaxis is defined as ______ of ________ along a _______ towards the site of injury.
locomotion of leukocytes
chemical gradient
78
Only endogenous substances can act as chemoattractants.
T/F
F
Both exogenous and endogenous substances can act as chemoattractants.
79
The most common exogenous agents are _____ products and some ____.
bacterial
Lipids
80
Endogenous chemoattractants include several chemical mediators:
______, particularly those of the ____ family (e.g., IL-8);
components of the ______, particularly ___; and
_________ metabolites, mainly ________
cytokines; chemokine
complement system; C5a
arachidonic acid (AA); leukotriene B4 (LTB4).
81
these chemotactic agents bind to specific _______ receptors on the surface of leukocytes.
Signals initiated from these receptors result in activation of second messengers that increase cytosolic calcium and activate small guanosine triphosphatases of the ___/___/___ family as well as numerous kinases
seven transmembrane G protein-coupled
Rac/Rho/cdc42
82
The leukocyte moves by extending _____ that pull the (front or back?) of the cell in the direction of _____.
• The net result is that leukocytes migrate toward the ______ in the direction of the ___________
filopodia
Back
Extension
inflammatory stimulus
locally produced chemoattractants.
83
• The nature of the leukocyte infiltrate varies with the ____________ and ______
age of the inflammatory response and the type of stimulus.
84
In most forms of acute inflammation ____ predominate in inflammatory infiltrate during the first 6 to 24 hours and are replaced by _____ in 24 to 48 hours
neutrophils
monocytes
85
After entering tissues, neutrophils are (short or long?) -lived; they undergo ______ and disappear within __________
Short ; apoptosis
24 to 48 hours.
86
Monocytes survive (shorter or longer?) than neutrophils and also proliferate in the tissues, and thus they become the dominant population in prolonged inflammatory reactions.
Longer
87
There are, however, exceptions to this stereotypic pattern of cellular infiltration.
• ________ bacteria - the cellular infiltrate is dominated by continuously recruited neutrophils for several days;
• viral infections -______ may be the first cells to arrive;
• some hypersensitivity reactions are dominated by activated ______,_______, and _________ (reflecting the immune response);
• Allergic reactions - ________ may be the main cell type.
Pseudomonas
lymphocytes
lymphocytes, macrophages, and plasma cells
eosinophils
88
• Agents that block ___, one of the major cytokines in leukocyte recruitment, are among the most successful therapeutics ever developed for chronic inflammatory diseases
TNF
89
Phagocytosis and clearance of the offending agent
• Recognition of microbes or dead cells induces several responses in leukocytes that are collectively called _______
• Activation results from signaling pathways that are triggered in leukocytes, resulting in increases in cytosolic ___ and activation of enzymes such as ____________ and ________
leukocyte activation.
Ca2+
protein kinase C and phospholipase A2.
90
The functional responses that are most important for destruction of microbes and other offenders are ________ and ______
phagocytosis and intracellular killing.
91
Phagocytosis
• Phagocytosis involves three sequential steps:
•________ and _____ of the particle to be ingested by the leukocyte;
• _______, with subsequent formation of a ___________; and
• ________ or _________ of the ingested material.
recognition and attachment
engulfment; phagocytic vacuole
killing or degradation
92
Phagocytic Receptors
•______ receptors, ______ receptors, and receptors for various ______ bind and ingest microbes.
Mannose; scavenger; opsonins
93
The macrophage mannose receptor is a _____ that binds terminal ______ and ——— residues of glycoproteins and glycolipids.
• The mannose receptor recognizes ______ and not ____ cells.
lectin
mannose and fucose
microbes; host cells
94
mannose receptor recognizes host cells
T/F
F
95
Macrophage integrins notably Mac-1 (CD11b/CD18), can not bind
microbes for phagocytosis.
T/F
F
It can
96
The efficiency of phagocytosis is greatly enhanced when microbes are _____ by specific proteins (opsonins) for which the phagocytes express (low or high ?) affinity receptors.
opsonized
High
97
The major opsonins are:
•__________,
• the ______________ of complement, and
• Certain ________, notably ______
IgG antibodies
C3b breakdown product
plasma lectins
mannose-binding lectin.
98
Engulfment
• After a particle is bound to phagocyte receptors, extensions of the cytoplasm (______) flow around it, and the plasma membrane pinches off to form a vesicle (_____) that encloses the particle which then fuses with a ______, resulting in _______
pseudopods
phagosome
lysosomal granule; phagolysosome
99
Phagocytosis is independent of polymerization of actin filaments
T/F
F
It’s dependent on
100
Intracellular destruction of microbes and debris
• Killing of microbes is accomplished by
_______________
___________, mainly derived from ______,
_______ enzymes that destroy phagocytosed debris.
• This is the final step in the elimination of infectious agents and necrotic cells.
• The killing and degradation of microbes and dead cell debris within neutrophils and macrophages occur most efficiently after activation of the phagocytes.
• All these killing mechanisms are normally sequestered in ____, to which phagocytosed materials are brought.
reactive oxygen species (ROS)
reactive nitrogen species,
nitric oxide((NO)
lysosomal; lysosomes
101
Reactive Oxygen Species.
• ROS are produced by the rapid assembly and activation of a multicomponent oxidase, _______ (also called _______), which (oxidizes or reduces)_______ and, in the process, reduces oxygen to superoxide anion.
• In neutrophils, this oxidative reaction is triggered by activating signals and accompanies phagocytosis, and is called the _______
NADPH oxidase; phagocyte oxidase
NADPH
respiratory burst.
102
ROS are produced within the ______ and _____, where they can act on ingested particles without damaging the host cell.
lysosome and phagolysosome
103
Enzyme ________ in the presence of a _____ such as Cl−, converts H2O2 to hypochlorite (OCl2)
myeloperoxidase (MPO)
Halide
104
The ___-___-____ system is the most efficient bactericidal system of neutrophils.
H2O2-MPO-halide
105
Nitric Oxide.
• NO, a (soluble or insoluble ?) gas produced from _____ by the action of _____________, also participates in microbial killing.
Soluble ; arginine
nitric oxide synthase (NOS)
106
• There are three different types of NOS:
______ (_NOS),
_______(_NOS), and
_________(_NOS).
endothelial (e
neuronal (n
Inducible (i
107
• eNOS and nNOS are constitutively expressed at (low or high?) levels and the NO they generate functions to ______ and as a ________, respectively.
Low
maintain vascular tone
neurotransmitter
108
__NOS, the type that is involved in microbial killing, is induced when macrophages and neutrophils are activated by cytokines (e.g., IFN- γ) or microbial products.
i
109
In macrophages, NO reacts with _________ to generate the highly reactive free radical _________
superoxide (O2 • )
peroxynitrite (ONOO−).
110
Lysosomal Enzymes and Other Lysosomal Proteins.
• Neutrophils have two main types of granules.
• The ———(___) granules contain lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase.
• The ______(____) granules contain myeloperoxidase, bactericidal factors (lysozyme, defensins), acid hydrolases, and a variety of neutral proteases (elastase, cathepsin G, nonspecific collagenases, proteinase 3).
smaller (or secondary)
larger azurophil (or primary)
111
The 2 types of granules In neutrophils can __________________, or the ___________
fuse with phagocytic vacuoles containing engulfed material
granule contents can be released into the extracellular space.
112
Acid proteases degrade ___ and _____ within the phagolysosomes,
bacteria and debris
113
Neutral proteases are capable of degrading various ___cellular components, such as ____,______, fibrin, elastin, and cartilage, resulting in the __________ that accompanies inflammatory processes.
Extra
collagen, basement membrane
tissue destruction
114
Neutral proteases can also cleave ____ and ___
C3 and C5
115
These harmful proteases, however, are normally controlled by a system of _______ in the serum and tissue fluids.
antiproteases
116
Foremost among these is ______, which is the major inhibitor of neutrophil elastase.
A deficiency of these inhibitors may lead to sustained action of leukocyte proteases as is the case in patients with α1-antitrypsin deficiency
α1-antitrypsin
117
•________ is another (besides α1-antitrypsin ) antiprotease found in serum and various secretions.
α2-Macroglobulin
118
Neutrophil Extracellular Traps
• Neutrophil extracellular traps (NETs) are extracellular ____ networks that provide a high concentration of ______ substances at sites of infection and prevent the spread of the microbes by _____________.
• They are produced by neutrophils in response to infectious pathogens (mainly _____ and _____) and inflammatory mediators (e.g., ____,___ [mainly _____], _____,_____).
fibrillar; antimicrobial
trapping them in the fibrils
bacteria and fungi
chemokines, cytokines; interferons
complement proteins, and ROS
119
The extracellular traps consist of a _______ of _______ that binds and concentrates granule proteins such as ________ and ______.
viscous meshwork
nuclear chromatin
antimicrobial peptides and enzymes
120
Leukocyte-Mediated Tissue Injury
• Leukocytes are important causes of injury to normal cells and tissues under several circumstances:
• In some infections that are _______, such as _______ and certain _____ diseases, the prolonged host response contributes more to the pathology than does the microbe itself.
• The inflammatory response is inappropriately directed against __ tissues, as in certain _____ diseases.
• The host reacts excessively against usually _____ environmental substances, as in _____ diseases, including _____.
Difficult to eradicate
tuberculosis
viral
host; autoimmune
Harmless; allergic; asthma
121
In all these situations, the mechanisms by which leukocytes damage normal tissues are the same as the mechanisms involved in antimicrobial defense,
• The contents of ______ are secreted by leukocytes into the _______ by several mechanisms.
lysosomal granules
extracellular milieu
122
Termination of inflammation
• Neutrophils also have short half-lives in tissues and die by apoptosis within a few hours after leaving the blood.
• In addition, as inflammation develops, the process itself triggers a variety of stop signals that actively terminate the reaction.
• These active termination mechanisms include
• a switch in the type of ____________ produced, from ___________ to _________
• liberation of _____________, including ____________ factor-β (TGF-β) and _____
arachidonic acid metabolite
proinflammatory leukotrienes to antiinflammatory lipoxins
anti-inflammatory cytokines
transforming growth
IL-10.
123
Acute inflammation has limited specificity
T/F
T
124
Innate immunity includes
______ cells
______ secreted by cells
_______ systems
Some cells like ___ cells, _____,_____
Epithelial
Mucus
Complement
mast, macrophages , the granulocytes
125
Neutrophils is under _____ immunity
Innate
126
Full meaning of TLRs
Toll -like receptors
127
TLR is present on cells of _____ immune system (_____ and ____)
Innate
Macrophages and dendritic cells
128
TLRs have the ability to recognize _____
PAMPs
129
Full meaning of PAMPs
pathogen associates molecular pattern
130
Examples of TLRs
CD14
131
Example of a PAMP
Lps on gram negative bacteria
132
TLR activation results in upregulation of ______
NF-kappa B
133
TLR also plays a role in adaptive immunity
T/F
T
134
TLR does not play a role in chronic inflammation
T/F
F
It does
135
Cyclopxygenases act on arachidonic acid to produce _____ like ___,—-,___ that mediate ____
Prostaglandins
PGI2, PGD2, PGE2
Vasodilation and increased vascular permeability
136
PG___ also mediates fever and pain
E2
137
Acute inflammation
Vasodilation is to _____ as increased vascular permeability is to _____
Arterioles
Post capillary venules
138
4 key mediators that actually attract and activate neutrophils?
LTB4
C5a
IL-8
Bacterial products
139
Lipooxygenase act on arachidonic acid to form _______ like ___,___,____,____
Leukotrienes
LTB4, LTC4, LTD4, LTE4
140
LT__ attracts and actuvates neutrophils
B4
141
Function of LTC4, LTD4, LTE4
Mediate Vasoconstriction , bronchospasm and increased vascular permeability
142
Mast cells are activated by :
1)_______
2)______ proteins ___ and ___
3) cross linking of cell surface __ by antigen
Tissue trauma
Complement ; C3a ; C5a
IgE
143
Once mast cell gets activated, it undergoes an immediate response of _____ that mediate vasodilation and increased vascular permeability
The delayed response of the mast cells is the production of _______ , particularly _____
Dumping histamine granules
Arachidonic acid metabolites
Leukotrienes
144
Complement proteins are a group of (pro or anti ?) inflammatory serum proteins that ______ inflammation and circulate as (active or inactive?) precursors
Pro
Complement
Inactive
145
Activation of complement proteins
______
______
_______
Classical pathways
Alternative pathway
Mannose-binding lectin pathway
146
Classical pathway of Activating complement proteins
____ binds to ___ or ___ that is bound to ____
C1
IgG or IgM
Antigen
147
Alternative pathway of Activating complement proteins
The ______ directly activate the complement
Microbial products
148
Mannose-binding lectin pathway pathway of Activating complement proteins
______ binds ______ on _____ and activates complement
MBL
Mannose
Microorganisms
149
Result of pathways of activating complement system
C3 convertase converts __ to __ and ___ which helps to produce _______ that coverts ___ to _____ and ____ which complexes with __________ to produce the ______
C3; c3a; c3b; c5 convertase; c5a; c5b
C6-C9
Membrane attack complex
150
Complement system key product functions
_____ trigger mast cell degranulation
——— is a chemotactic for neutrophils
_____ is an opsonin for phagocytosis
_____lyses microbes by creating holes in their membranes
C3a and C5a
C5a
C3b
MAC
151
Hageman factor
-an inactive (anti or pro?) inflammatory protein produced in the ____
-activated upon exposure to ______ or _____
pro; liver
subendothelial or tissue collagen
152
Activated Hageman factor cleaves _____ to ____ which mediates ___,____, and _____
High molecular weight kinninogen(HMWK)
Bradykinin
Vasodilation, increased vascular permeability, and pain
153
Key mediators of redness and calor in acute inflammation??
Bradykinin
Prostaglandins
Histamine
154
Key mediators of swelling in acute inflammation??
Histamine
Tissue damage
155
Key mediators of pain in acute inflammation??
Bradykinin
PGE2
156
Fever is a cardinal sign of acute inflammation
T/F
T
157
Fever is mediated by ____ and ___ released by ____ to increase ____ activity in _____ cells of the _____ thereby increasing ____ which increases the temperature
IL1 and TNF
Macrophages
COX
Perivascular cells
Hypothalamus
PGE2
158
P- selectin is mediated by _____
E-selectin is induced by ______
Histamine
IL1, TNF
159
Cellular adhesion molecules are up regulated on ———- by ________
Integrins are upregulated on ______ by _______
Endothelium; TNF and IL1
Leukocytes; C5a and LTB4
160
Leukocyte adhesion deficiency
Autosomal recessive defect of _______ subunit
Integrins
CD18
161
Pus is basically dead ______ sitting in fluid
Neutrophils
162
Chediak-Higashi syndrome
________ defect
Characterized by impaired ______ formation
Protein trafficking
Phagolysosome
163
Neutrophils granules are produced by the _____
Golgi apparatus
164
______ are the managers of the acute inflammatory process
Macrophages
165
Excessive inflammation ( _____ )
sepsis
166
Bradykinin is degraded by ______
ACE
167
___ inhibitors can raise bradykinin levels
ACE
168
Dangerous side effect of too much bradykinin is _____
angioedema
169
Bradykinin is Also degraded by ________ (complement system) and its deficiency causes ________
C1 inhibitor
hereditary angioedema
170
Bacterial infections:______
Viral infections: _______
fungal and parasitic infections: _________
neutrophils (neutrophilia)
lymphocytes (lymphocytosis)
Eosinophils
171
Acute phase reactants
Are _______
Levels (rise or fall?) with inflammation (acute or chronic)
Mostly produced by ____
Synthesis increased by cytokines often ___
Serum proteins
Rise
liver; IL-6
172
Mention 5 APRs
C-reactive protein
Serum amyloid A
Ferritin
Hepcidin
Fibrinogen
173
C- reactive protein
Liver synthesis in response to ___(___)
Binds _____ polysaccharides
Activates ______ system
IL-6 (macrophages)
bacterial
complement
174
There is Diagnosis of iron deficiency during infection
T/F
T
175
Hepcidin
________ properties
Inhibits ____ transport
Contributes to _____ of chronic disease
Anti-bacterial
iron
anemia
176
Hepcidin
Binds to ______ in enterocytes and ———to prevent iron release
Iron trapped in cells as ______
ferroportin; macrophages
ferritin
177
ESR is decreased by APRs in inflammation
T/F
F
Increased
178
RBC is ______tively charged
Negative
179
ESR
Determined by balance of factors
Pro-sedimentation: ____, especially ____ (sticky)
Anti-sedimentation: ______
APRs
fibrinogen; negative charge of RBC
180
Some APRs are inhibited by cytokines and their levels (rise or fall?) in inflammation
List them
Fall
Albumin
Transferrin
Transthyretin
181
Neutrophils circulate for approximately _____ days then die unless activated
5 days
182
Normally, the fluid portion of the blood is in the _______ while the cellular portion is in the ________
Periphery
Central
183
Functions of TNF and IL-1
CAM expression
E selectin expression
Fever
184
Chemokines include???
IL8
PGD2
LTB4
C5a
5-HETE
185
List 2 antiproteases
Alpha 1- antitrypsin
AlphA2- macroglobulin
186
anti-inflammatory cytokines, including
transforming growth factor-β (TGF-β)
IL-10.
187
List 5 things from mast cells
Histamine
Serotonin (in rodents, not humans)
Prostaglandins
Leukotrienes
Platelet activating factor
