Test 1: lecture 6 inflammation Flashcards
3 main steps of inflammation
Vascular (stromal) responses
Migration and activation of leukocytes
Systemic reaction
5 signs of inflammation
- Rubor – redness
- Tumor – swelling
- Calor – heat
- Dolor – pain
- Functio laesa - Loss of function
Inflammation can cause further tissue damage and lead to healing by ___ or ___
REGENERATION
fibrosis (SCAR FORMATION)
phlebitis
fungal abomasitis
another name for redness
rubor
another name for swelling
tumor
another name for pain
dolor
another name for heat
calor
what are the two principle components of inflammation
Vascular reaction – involves fluid and plasma proteins (e.g. complement and fibrin), blood vessels, and extracellular matrix elements (increased blood flow and increased permeability)( vasodilation- NO, bradykinin,PGD2 permeability- histamine, bradykinin, PGE2, C5, C3, IL-1, TNF)
Cellular reaction – neutrophils, monocytes, eosinophils, lymphocytes, basophils, platelets, tissue mast cells, fibroblasts, and macrophages. Important role for extracellular matrix such as fibrous proteins (collagen and elastin) adhesive glycoproteins (fibronectin, laminin) and proteoglycans (movement of immune cells) chemotaxis- C5, IL-1, TNF
acute vs chronic inflammation
acute: rapid, short duration, neutrophils and edema
chronic: long, lymphocytes, macrophages, fibrous connective tissue and necrosis
what is the most important cell in acute inflammation
neutrophils
what are the most common cells during chronic inflammation
lymphocytes and macrophages
neutrophil
acute inflammation
monocyte which turns into a macrophage
lymphocyte -chronic inflammation
what kind of cells
Pleural fluid (exudate/vascular) from a dog with bacterial infection and pyothorax (what is pyothorax)
unhealthy neutrophils
how does histamine effect capillary blood flow
will vasodilate → increase blood flow (increase redness and heat)
4 steps of the vascular reaction on acute inflammation
- capillary blood flow increases (histamine, NO→ redness and heat))
- increased permeability of the vessel walls in the veins mostly (Starling relationship-bradykinin, histamine, C5, C3, PGE2)
- white blood cell and fluid leave the vessels = neutrophil emigration (tumor→ swelling-chemotaxis- IL-1 TNF)
- white blood cells are activated
____ and ___ are vasodilators
histamine and NO
increased blood flow causes which cardinal sign of inflammation
rubor- redness
calor- heat
During inflammation, blood flow ___and vessels ___and become permeable to vascular elements, allowing them to exit and enter sites of injury.
increases
dilate
increased vascular permeability is the cause of what cardinal sign
tumor- swelling
___ is increased blood flow
hyperemia
___ is the earliest manifestation of inflammation
Vasodilation
explain osmotic pressure
the pull of proteins to pull fluid back into the vessels
if proteins leak out there is less osmotic pressure and leads to a build up of fluid outside vessels → edema
explain hydrostatic pressure
the pressure to move things out of the vessel
opposite to osmotic pressure
histamine and bradykinin will cause ___ change their vascular permeability
HEV→ will cause gaps to form between vascular endothelium and allow fluid to leave
effects HEV in 15-30 mins, not capillaries and arterioles. those are effected 2-12 hours later by cytokines
journey from vessel lumen to interstitial tissue
Extravasation
the cellular reaction of inflammation involves what two steps
extravasation and phagocytosis
movement of cells out of the vessels and activation of cells to clean up
Normally RBC ’s form a central column and leukocytes are
displaced peripherally. Blood stasis and vessel dilation during inflammation produces greater leukocyte ___
margination
what causes rolling of leukocytes
selectins on the endothelium of blood vessels
sialyl-lewis X on the leukocyte
adhesion is by the ___ on the leukocyte and the ___ on the endothelium
integrins
ICAM and VCAM
b2 integrins (LFA-1 and Mac-1) bind ICAM-1 b1 integrins (VLA4) bind VCAM-1 (1o endo. adhesion molecule)
transmigration through the endothelium is by ____ on the endothelium and ___ on the leukocyte
PECAM
CD31
what are some things that can activate leukocytes
Arachidonic acid production
ysosomal enzyme production (degradative enzymes like
elastase and collagenase but also antibacterial such as
lysozyme and myeloperoxidase)
cytokine secretion
activation of adhesion molecules (integrins)
fluid, proteins, and blood cells that escape into interstitial spaces or the body cavities. Specific gravity > 1.020. caused by increased vascular permeability
exudate
suppurative exudate
pus
composed of neutrophils and dead cells (pus). Purulent is a synonym of suppurative. An abscess is a localized form of suppurative inflammation
Fibrinous exudate
increased vascular permeability during acute inflammation permits leakage of plasma proteins including fibrinogen, which is cleaved into fibrin and polymerizes into clots. This can occur in seconds.
Can later be replaced by fibrosis, which is a distinct process involving deposition of connective tissue by fibroblasts.
serous exudate
blister
fluid rich in protein on body surface → leakage from burns
exudate vs transudate
exudate → SG > 1.02 → contains proteins→ caused by increased vascular permeability
transudate→ SQ less then 1 → low protein content → caused by increased hydrostatic imbalances or a decrease in oncotic/osmotic pressure
transudate
fluid with low protein content (<1% albumen) with specific gravity < 1.012.
caused by an increased osmotic or hydrostatic imbalance across vessel wall or a decrease in colloid (oncotic) pressure w/o an increase in permeability of vessel wall.
ultrafiltrate of blood plasma
general term for increased fluid in the interstitium with the only exception being the LUNG where excessive fluid in the alveolar lumen is also defined as edema.
edema
fluid in the serous cavities
effusion
exudate
opsonination
prepare for eating
when a pathogen is coated in antibodies, complement or lectins and it makes it easier for the body to find and kill that pathogen
what enzyme is used by macrophages to kill bacteria
myeloperoxidase
within macrophages, myeloperoxidase makes hypochlorite (bleach) from ___. Most efficient killing system in neutrophils.
hydrogen
peroxide
Inflammatory mediators are produced by tissues and secreted into plasma (___ etc. must be activated) or produced locally by cells (___ etc.)
complement, kinins,
histamine, lysosomal enzymes,
list two Vasoactive amines (increase vascular permeability)
histamine
serotonin
Factor XIIa
hageman factor
starts the clotting pathway that leads to Fibrinogen (thrombin) → Fibrin
clot formation
Type 1 hypersensitivity pathway is by ___
mast cells, basophils and platelets produce histamine
causes arteriolar dilation, increase in venule permeability
principle mediator of immediate transient phase of
increased vascular permeability (endothelial H1 receptors)
Histamine is produced primarily by ___
mast cells
Complement system causes ___ vascular permeability, chemotaxis, & ___ pathogens.
increased
opsonizes
3 pathways of complement
3 outcomes of complement are
- proteolytic fragments (C3a and C5a) ___ other cells
- induction of microbe ___
___ by membrane attack complex (MAC)
activate→ inflammation
phagocytosis
cell lysis
Fibrinogen (____) → Fibrin
Thrombin
kinin system
breaksdown clots
plasmin is used to split fibrin
will produce bradykinin → cause pain
what is a by product of the kinin system that causes pain
bradykinin
what cardinal signs are caused by bradykinin
increase vascular permeability like histamine (tumor-swelling, calor-heat)
dilation of blood vessels (rubor-redness)
pain (dolor)
____of clotting pathway is activated to XIIa by collagen, basement membranes, negatively charged surfaces.
Hagemann Factor (Factor XII
___ converts prekallikrein to kallikrein, which converts plasminogen to plasmin, which lyses fibrin and activates C3.
Factor XIIa
Interaction between clotting, inflammatory, complement and fibrinolytic systems by activated ___
Factor XIIa.
pain is due to ___
bradykinin
___ is found in triglyceride in the plasma membrane and is a lipid derived mediator
arachidonic acid
___ are used to covert cell membrane to AA
phospholipases
steroid inhibit this step
Cyclo-oxygenases (COX-1 and COX-2) convert AA into ___
prostaglandins, thromboxane, and prostacylines.
prostacyclin (PGI2) cause ___
vasodilation, and inhibit platelet aggregation
arachidonic acid (COX1 and COX2) → PGG2 → prostaglandins, thromboxane, and prostacylines. (PGE2, PGD2, PGF2a, PGI2, TXA2
prostaglandins cause
vasodilation and potentiate edema
arachidonic acid (COX1 and COX2) → PGG2 → prostaglandins, thromboxane, and prostacylines. (PGE2, PGD2, PGF2a, PGI2, TXA2
Thromboxane cause ___
vasoconstriction, promote platelet aggregation
arachidonic acid (COX1 and COX2) → PGG2 → prostaglandins, thromboxane, and prostacylines. (PGE2, PGD2, PGF2a, PGI2, TXA2
arachidonic acid (_____) → leukotrienes and lipoxins
5- lipoxygenase
leukotrienes cause
vasoconstriction, bronchospasm and increased permeability
Lipoxygenases produce ____from arachidonic acid
leukotrienes and lipoxins
___ is Constitutively expressed - AA production for daily needs.
COX-1
which pathway did Vioxx target
COX-2 caused cardiomyopathy
trying to prevent AA from turning into prostaglandins(vasodilation and edema), thromboxane (vasoconstriction and promote platelet clumping) , and prostacyline (vasodilation and inhibit platelets) that cause inflammation
(aspirin and other NSAIDs lead to prolonged bleeding because they inhibit ___ production.)
TXA2 thromboxane
PGI2
PGI2 (prostacylin) – from vascular endothelium, potent vasodilator,
inhibits coagulation, major product of endothelium.
TXA2 – major product of ___. Causes platelet ____and
vaso___ , coagulation, is short lived
platelets
aggregation
constriction
___ are involved in the pathogenesis of ASTHMA
LTC4, LTD4, LTE4 → cause vasoconstriction, bronchospasm and increased permeability
LOX inhibitors
Used for asthma in cats and recurrent airway obstruction in horses)
May be useful in treatment of asthma where leukotrienes play a role in pathogenesis (Fenleuron, Zileuton – 5 lipoxygenase inhibitor)
how do steroid effect inflammation
decrease expression of genes encoding COX-2, PLA2 directly, IL-1,
TNF, and iNOS.
increase expression of anti-inflammatory genes, inhibit AA release from membranes.
____ - major pro-inflammatory cytokines with systemic effects.
IL-1 and TNF
IL-1 and TNF are produced by
activated macrophages
what 4 effects do IL-1 and TNF have
acute-phase reactions
endothelial effects
fibroblast effects
leukocyte effects
IL-1 and TNF released from leukocyte (macrophages), act as
pyrogens – increase COX activity and PG synthesis from ___
AA
IL-1, IL-6, and TNF drive a 100 fold increase in production of key
liver proteins including: • C-reactive protein, fibrinogen, ___
serum amyloid A protein (SAA)
Leukocytosis
IL-1 and TNF lead to an increase in the number of immature cells (left
shift) released from bone marrow.
histamine and serotonin and made by ___ and cause a ___ in permeability
mast cells and platelets
+
bradykinin are made by ___ and cause a ___ in permeability
plasma substrate (made by fibrin breakdown pathway)
+
pain
___ is made by mast cells and causes Vasodilation, pain, fever
prostaglandins
___ are made by macrophages and cause Acute-phase reactions, endothelial activation, fibroblast activation
IL-1 and TNF
___ are made by macrophages and endothelium and cause vasodilation and cytotoxicity
nitric oxide
outpouring of thin fluid.
serous effusion
fibrinous inflammation
increased vascular permeability
fibrinogen leaves vessels and gets turned into fibrin
typical of body lining/cavity inflammation
___ type of inflammation is common for the body lining/cavity
fibrinous
____ is. typical of mucosal surfaces, exudate resulting from overproduction of mucus mixed with neutrophils and other leukocytes.
catarrhal inflammation
suppurative inflammation
pus → neutrophils, necrotic cells, edema.
abscess
can be walled off
3 outcomes of acute inflammation
complete resolution
healing by connective tissue replacement (fibrosis)
progression to chronic inflammation
during complete resolution of acute inflammation what happens
vascular permeability normalized
edema reabsorbed
debris eaten
macrophages removed
3 causes of chronic inflammation
persistent infection
exposure to toxin
autoimmunity
___ are the dominant cells in chronic inflammation
Macs and lymphocytes
Macrophages induce____ activation and proliferation (IL-1 and TNF), collagen deposition, and angiogenesis.
fibroblast
Tissue ____ is one of the hallmarks of chronic inflammation.
destruction
develop from activated B lymphocytes, produce antibody
against persistent antigen in the inflammatory site or against altered tissue components.
plasma cells
activated by IgE in parasitic infections. ___ granules
contain major basic protein, which is toxic to parasites and mammalian epithelial cells.
eosinophils
Eosinophil
____- widely distributed in connective tissues. Fc receptors bind
the Fc portion of IgE antibody. IgE antibodies bound to Fc receptors specifically recognize antigen, and the cells release mediators, such as histamine and products of AA oxidation.
mast cells
two cell types that make up granuloma
epithelioid macrophage
multinucleated giant cell
granulomas have ___ macrophages and ___ cells. They are also usually surrounded by ___ and are caused by ___
epithelioid macrophages
multinucleated giant cell
fibrosis
delayed type hypersensitivity (type 4)
____ reactions are the driving cause of granulomas, i.e. this is a form of immunopathology
Delayed Type hypersensitivity (DTH) (Type 4 reaction)
____ is an epithelioid macrophages forming granulomas with neutrophils in center of granuloma and pus
Pyogranulomatous inflammation
granuloma
List the five cardinal signs of inflammation and the underlying pathophysiological basis of each
Rubor – increased blood flow and tissue perfusion
b. Calor – increased blood flow and tissue perfursion
c. Dolor – bradykinin and other pain mediators, some prostaglandins and leukotrienes
d. Tumor – increased vascular permeability and fluid loss from vessels
e. Loss of function – tissue destruction, fibrosis, edema
Conserved steps of Acute Inflammation
• Initiated by injury or agent, mast cells activated, tissue resident macrophages activated. ___blood flow due to ___
Increase
vasodilation.
Neutrophils release cytokines (e.g. IL-1, TNF) and lipid mediators. IL-1 and TNF ____ vascular permeability and can have systemic effects (____)
increase
fever, nausea, malaise
Know the difference between an exudate and a transudate. What are the key differences between these fluids and how is each formed?
- *Exudate** – fluid, protein and cells that escape into interstitial spaces or the body cavities. Specific gravity > 1.020, high protein, mainly neutrophils
- due to major increase in vascular permeability
- *Transudate** – fluid with low protein content with specific gravity < 1.012
- due to Increased hydrostatic (hypertension) imbalance across vessel wall or a decrease in colloid (oncotic - hypoproteinemia) pressure due to renal disease, burns, hepatic disease with decreased albumen production. Also seen in early acute inflammation. - ultrafiltrate of blood plasma
____ is composed of neutrophils and dead cells (pus). example: An abscess
Suppurative exudate
___ has increased vascular permeability during acute inflammation and accumulation of fluid with high protein and low cell numbers with S.G > 1.02. Associated with endothelial cell injury and leakage of larger MW proteins such as fibrinogen.
Fibrinous exudate
___ are lesions characterized by accumulation of fluid rich in protein on body surfaces e.g. oozing of fluid from burns or Blisters
serous exudate
___ is tissue response comprised of secretion or accumulation of thick
gelatinous fluid containing mucus from mucous membranes (goblet cells and mucous glands). Seen with allergic and chronic airway inflamation and autoimmune GI disease
catarrhal exudate
___ cause expression of E-selectins on endothelium in 1-2 hours.
IL-1 and TNFa
Cyclo-oxygenases (COX-1 and COX-2) convert AA into ___. Targets of NSAIDS, COX inhibitors, steroids.
• prostaglandins, thromboxane, and prostacylines. (PGE2, PGD2, • PGF2a, PGI2, TXA2).
Lipoxygenases produce ___ from AA
leukotrienes and lipoxins
Glucocorticoids decrease expression of genes encoding ___, IL-1, TNF, and iNOS.
COX-2, PLA2 directly
Complement proteins orchestrate immune cell activation and pathogen killing by 3 main mechanisms. What are these mechanisms and which complement proteins/fragments are effectors of these mechanisms
Phagocytosis – ___ are opsonins on bacteria and increase phagocytosis by neutrophils and macrophages
C3b and iC3b
Myeloperoxidase makes ___ from hydrogen peroxide.
hypochlorite (bleach)
