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169 Cards in this Set

  • Front
  • Back
the holy trinity of acute inflammation
increased vascular permeability
leukocyte infiltration
caused by increased viscosity due to loss of plasma
six ways to increase vascular permeability
1. detachment of cell-cell junctions due to histamine (immediate transient) and IL-1 / TNF (6 hours to 24)
2. delayed prolonged response - this begins at 2-8 hours and may last days. due to secondary cytokines or perhaps endothelial apoptosis due to uv damage
3. endothelial cell injury (burns, radiation)
4. leukocyte mediated damage
5. vesiculovacuolar organelle increases transcytosis
6. leakage from new blood vessels (w/o cell-cell yet)
the beta 2 integrins
lfa-1 and mac-1
receptor for p selectin
sialyl lewis x
receptor for e selectin
sialyl lewis x
ligand for beta 2 integrins
lfa-1 and mac-1 bind to

ligand for the beta 1 integrin
VLA-4 binds to

the beta 1 integrin
examples of Immunoglobulin family molecules on endothelial cells
histamine exposure causes redistrubtion of ____ to the endothelial cell surface
P selectin
IL-1 and TNF cause increased expression of __, __, and __ in endothelial cells
E Selectin
in leukocytes, chemokines cause increased affinity of ___ for their ligands
LFA-1 and Mac-1
homotypic interaction between ___ molecules on endothelium and leukocytes mediate extravasation
in acute inflammation, neutophils dominate in hours ___ to ___, and monocytes dominate in hours ___ to ___

exogenous bacterial products
arachadonic acid breakdown produccts

are all chemotactic for ____
what are some components of leukocyte activation?
production of cytokines
production of arachadonic acid metabolites
degranulation / secretion of lysosomal enzymes
increased cell adhesion molecule expression / increased affinity of integrins
2 major opsonins and key difference
immunoglobulins (Fc fragment)

complement is covalent!
scavenger receptor
expressed on macrophages helps them recognize bacteria for phagocytosis
major basic protein
produced by eosinophils
works especially on parasites
increases permeability to kill them
what do lactoferrin and defensins have in common?
they are secreted by leukocytes to increase membrane permeability of bacteria to kill them
how can urate crystals cause lysosomal enzyme release?
they puncture lysosomes when engested
chronic granulomatous disease
reccurent bacterial infections because of a defect in the NADPH oxidase
defect in the beta 2 integrins, leukocytes cant bind tightly
defect in fucose metabolism, and no sialyl lewis x, leukocytes cannot roll
defect in vesicle trafficking
lysome cant fuse with phagosome

recurrent infections

also hypopigmentation
most common clinical cause of neutrophil deficiency?
neutropenia - cuased by cancer chemotherapy or metastatic tumor replacing bone marrow
what are some anti-inflammatory molecules produced to end the inflammatory response?
tgf-beta (anti inflammatory cytokine) and lipoxins
primary inducer of cytokines?
what things can activate platelets to release serotonin (and just generally activate them?)
PAF (platelet activating factor)
antigen-antibody complexes
what activates complement in the lectin pathway
plasma MBL
which complement component activates arachonic acid metabolism?
which complement component is a powerful leukocyte chemoattractant?
which complement component is an opsonin?
2 molecules that inhbit complement activation?
c1 inhibitor
decay activating factor
paroxysmal nocturnal hemoglobinuria
defect in decay activating factor causes activation of complement -> hemolysis and anemia

your red cells "decay"
hereditary angioneurotic edema
defect in c1 inhibitor -> episodic life threatening edema b/c complement gets activated

c1 inhibitor is neurotic
effects of bradykinin
increased permeability
increase vascular permeability
chemotactic for leukocytes
how does thrombin increase leukocyte attachment to endothelium
via PARs (dont know which cells these are on...)
how does plasmin contribute to complement cascade
it cleaves C3 (c3 tickover)
transcellular biosynthesis
occurs in leukotriene and lipoxin synth
what produces PAF?
MAST CELLS!!! (after an activating stimulus such as IgE activation)

and other leukocytes
what does PAF do?
PAF can elicit most of signs of acute inflammation

platelet activation and release
increased vascular permeability
increased leukocyte adhesion
leukocyte chemotaxis
the major cytokines of inflammation
IL-1 and TNF
what is the major source of IL1 and TNF
activated macrophages
systemic acute phase response
initiated in response to IL-1 and TNF
1. fever
2. anorexia
3. lethargy
4. neutrophilia
5. release of corticotropin from pituitary and corticosteroids from adrenal
6. hemodynamic effects of septic shock (3)
what are the hemodynamic effects of septic shock?
1. hypotension
2. tachycardia (brr)
3. acidosis
cachexia is associated with which cytokine
4 classes of chemokine receptors?
CXC chemokines recruit ____
IL-8 is a ____ chemokine

recruits neutrophils
CC chemokines recruit ____
all but neutrophils
C chemokines recruit _____
a C chemokine
a CX3C chemokine
fractalkinin -recruits monocytes and lymphocytes

soluble and membrane bound version
eotaxin is a ____ chemokine
NO's effects on platelets
decreases platelet aggregation / activation / adhesion
what activates eNOS and nNOS
increased cytoplasmic calcium
what induces iNOS?
IFN-gamma - think granuloma and activated macrophages

IL-1 and TNF - think septic shock
which NOS is important in septic shock and why?
cytokines IL-1 and TNF induce iNOS in activated macrophages, and this helps lead to the widespread vasodilation
what holds proteases in check
serum and tissue antiproteases such as alpha 1 antitrypsin
2 serum proteins that protect from ROS?
hypoxia-induced factor 1-alpha
produced by cells deprived of oxygen, can induce an inflammatory response (think reperfusion injury)
how do necrotic cells cause inflammation
uric acid
serous inflammation
eg blister, pleural effusion
modest increase in permeability with low specific gravity transudate
fibrinous inflammation
eg fibrinous pericarditis, fibrinous pleuritis

marked increase in vasc perm which allows leakage of fibrinogen which is turned into fibrin by coagulation cascade and is deposited on serosal surface
suppurative purulent inflammation
=pus = exudate with high protein content, neutrophils, and cell debris
localized collection of purulent inflammatory exudate accompanied by liquefactive necrosis
erosion of EPITHELIUM due to sloughing off of inflammed necrotic tissue
holy trinity of chronic inflammation
1. infiltration by macrophages, lymphocytes, and plasma cells (mononuclear cells)
2. tissue destruction due to persistent injury and the inflammatory cells
3. attempts at healing - neovasculization and fibrosis
what is the best macrophage activator
interferon gamma - they love this shit - it's like crack
what do macrophages make that TH1 cells love the shit out of?
a focal accumulation of activated macrophages walled off by t-lymphocytes.

the t-lymphocytes produce interferon gamma and the macrophages produce IL12
giant cell
activated macrophages -> epithelioid macrophage -> fuse to form giant cells
foreign body granuloma
foreign body cannot be gotten rid of and thus causes chronic inflammation in the form of a granuloma
can a granuloma be acute inflammation
what is a tubercle?
an immune granuloma with a core of central caseous necrosis
inflammation of the lymph nodes
inflammation of the lymphatics - can make red lymphangitic streaks
what is the first line of defense in bacteremia?
phagocytes in the spleen, liver, and bone marrow
systemic inflammatory response syndrome is a very severe activation of the acute phase response
what causes the acute phase response?

what are components of the acute phase response
acute phase response is due to the systemic effects of cytokines

2.acute phase proteins
4. increased pulse and blood pressure, rigors, chills, anorexia, somulence, malaise, lethargy too?
how do IL1 and TNF cause fever?
they increase the production of PGE2 in the hypothalamus and increase the temperature set point
how does endotoxin cause such systemic effects?
it causes massive release of IL1 and TNF
what are some of the acute phase proteins that are increased in the systemic response to IL1 and TNF?
serum amyloid A
C reactive protein
what is a shift to the left?
it occurs in the acute phase response. immature neutrophils mobilize from the bone marrow, and thus there are more of them in the blood
leukemoid reaction
when leukocyte levels are more than 40,000 / mL
viral infections cause what shift in leukocyte #
bacterial infections cause what shift in leukocyte #
parasitic infections cause what shift in leukocyte #
allergic reactions cause what shift in leukocyte #
what do SAA and CRP do?
they bind to microbial cell walls and act as opsonins
what is the clinical triad of septic shock?
1. cardiovascular failure (hypotension, decreased CO, etc)
2. DIC
3. hypoglycemia
why does diabetes result in problems with WBC adhesion?
glycated receptors!
how do cirrhosis and sarcoidosis affect chemotaxis?
they increase C5 inactivators
what do mbl, saa, and crp all have in common
they are plasma proteins and are opsonins. they have receptors on macrophages
which mediators of inflammation are preformed?
lysosomal proteases

what are 1st, 2nd, and 3rd waves of inflammatory mediators
1. presynthesized cellular
2. newly synthesized cellular
3. hepatic synthesized (acute phase proteins like complement)
why do alcoholics have diminished response to infection?
their liver is damaged and doesnt make acute phase proteins like it should!
which inflammatory mediators are not premade and must by synthesized?
AA products,
what enzyme do steroids downregulate in inflammation?
blocks cyclooxygenase
relation b/t fibrinous pericarditus and friction rub?
kidney failure
friction rub
irritation of pericardium
fibrinous pericarditis
hemorrhagic exudate?
rickettsial infection that infects the endothelial cells
pseudomembranous exudate?
clostridium diphtheria (DIPHTERIA!)

diphtheria toxin kills epithelial cells

layer of necrotic debris forms on top of the epithelium (pseudomembrane)
when can acute inflammation form a scar
in tissue that can't regenerate (heart)- it was never chronic inflammation

in an abscess - it was neutrophils so it was never chronic . they can do enough damage to for m a sacr
macrophages in connective tissue
langerhans cells
macrophages in skin
is granulomatous inflammation a kind of chronic inflammation
maybe, but Dr. Anderson says there are 3 kinds, acute , chronic, and granulomatous
acute tubular necrosis
when the proximal convoluted tubule epithelial cells die but leave the BM behind. they can repopulate and re-line the BM. just put the pt on dialysis and they will survive
when hepatocytes repopulate in cirrhosis, what is wrong with the new tissue?
bile duct has no superstructure, so biliary epithelium doesnt know where to regrow. you just have green nodules full of bile and bile stasis
difference b/t healing by primary and secondary intention?
healing of a surgical incision vs healing of a large tissue defect with lots of scar tissue created
granulation tissue
fibroblasts and endothelial cells in ECM matrix.
transition in collagen types in wound healing
III -> I
III is seen early on
I is the tough crosslinked stuff
when will wound reach 70-80% of orig strength
3 months
where is procollagen cleaved and crosslinked
where are lysines oxidized in collagen formation
where are lysine and proline hydroxylated in collagen synthesis
why is vitamin C needed for collagen synth?
hydroxylation of proline and lysine
what is a formyl methyl protein?
a bacterial protein which dendritic cells and macrophages, etc have receptors for
what are lipotechoic acids?
associated with gram pos bacteria, and we have receptors for them on innate immune system cells
Toll-like Receptors bind (innate immune sys)
LPS receptor
which receptor activates NFkB?
Toll like receptor

promotes survival
which cells express TLR?
dendritic cells
mucosal epithelium

all these cells come in contact with invaders
what binds to flagellin and zymosan?
bacterial DNA which TLR's recognize
why do dendritic cells express TLRs?
they kick off the innate immune system
NOD proteins
like TLR but are intracellular and recognize intracellular organisms and pieces of phagocytosed organisms
why is C reactive protein reactive?
it opsonizes and activates complement!
where are cytokines of innate immunity produced? adaptive immunity?
innate - activated macrophages (and NK cells too)

adaptive - lymphocytes
is IL-1 more adaptive or innate?
is TNF more adaptive or innate?
is IL-12 more adaptive or innate?
is IL-2 more adaptive or innate?
is IL-4 more adaptive or innate?
is IL-5 more adaptive or innate?
what inhibits synthesis of IL-1, TNF, and IL-12?

this is part of the antiinflammatory effect
what makes the adaptive immune system's cytokines?
TH1 and TH2 cells. and in much lower concentrations
are adaptive or innate cytokines local acting?
adaptive are in lower conc and more locally acting
what is the synthesis inhibitor of adaptive imm sys cytokines?
how does cyclosporin decrease immune rejection
it decreases the synthesis of adaptive immune system cytokines by T cells such as IL-2, IL-4, and IL-5
what is the typical cytokine signal transduction mechanism?
jak stat
what makes TNF?
activated macrophages
what stimulates macrophages to make TNF?
which 2 cytokines are endogenous pyrogens?
IL-1 and TNF
what does TNF do to endothelium?
it activates it and upregulates expression of cell adhesion molecules
what is TNF's effect on the liver
it increases acute phase protein production
what effect do high concentrations of TNF have on myocardial contractility and the blood vessels?
they decrease myocardial contractility and cause profound vasodilation. this leads to cardiovascular collapse
what 2 diseases are treated with anti-TNF antibodies?
rheumatoid arthritis

crohn's disease
what is complication to anti-TNF therapy?
susceptibility to infection, esp TB and histoplasmosis
what stimulates IL-1 production
LPS and TNF (waves)
what is one critical difference between IL-1 and TNF?
TNF has apoptotic effects but IL-1 does not
why does prostate cancer like to metastasize to bone?
prostate cancer cells express chemokine receptors for a bone chemokine.
what are the salient features of IL-12
IL-12 is the gateway b/t the innate and adaptive immune responses

APC's (like activated macrophages and dendritic cells) respond to pathogens with their TLR's and then produce IL-12 to activate lymphocytes

stimulates production of interferon gamma (which activates macrophages)
increases cytolytic function of NK and CTL
stimulates differentiation of TH into TH1 cells, effecting a cellular response

it activates TH1 lymphocytes to produce more cytokines
what is the gateway from the innate to the adaptive immune system?
IL-12 produced by macrophages upon interacting with T cells
what cytokine stimulates differentiation of TH to TH1 cells?
what is the difference between IFN alpha and beta
alpha is a family of interferons produced by one cell type

beta is one interferon produced by many cell types

they both signal thru the same receptor activating a jak/stat pathway
effects of type I interferon?
1. inhibit viral replication
2. increase expression of MHC type I
3. antiproliferative
how do type I IFN stop viral infection?
1. inhbit viral reproduction
2. antiproliferative
3. increase expr of MHC I
IFN alpha is used to treat ____
hepatitis C
IFN beta is used to treat ____
multiple sclerosis
what 2 cell types produce IFN gamma?
NK cells and TH1 cells
what is a fun enzyme that IFN gamma induces?
iNOS (increases NO killing by macrophages)
anti inflammatory cytokine
1. inhibits immune activation
2. decreases macrophage activation
comes 3rd right after TNF and IL-1
increases acute phase proteins and neutrophilia
*shown to be stimulatory to innate and inhibitory to adaptive immune response -weird. definitely strong innate
IL-15 is important for viral infection!! IT is an early stimulator of NK proliferation in response to viral infection
synergizes with IL-12 to increase IFN-gamma production