chapter 3: inflammation Flashcards
describe the formation of granulomas (tubercles)
MO MHC2 CD4+ cell presentation—> MO secretion of IL-12 –>induce TH1 cell type–>IFNY release –> formation of M1 epitheliod histiocytes and giant cells –> more IL-12 secretion to continue the cycle
what is proud flesh
excess granulation tissue that need to be removed for proper scar formation
describe the process of adhesion
binding of neutrophilic integrins to CAMs on the endothelium
integrins upregulated by C5a and LTB4
CAMs unregulated by TNF and IL-1
what are the 3 general phases of acute inflammation
- fluid phase (swelling from dilation and increase vascular permability)
- neutrophil phase (recruitment of neutrophils)
- Macrophage phase (activation of consequential response of repair or adaptive immunity)
describe the process of transmigration/diapidesis
- occurs in post capillary venule
- uses PECAM-1 (CD31) intracellular adhesion molecule to transmigrate through the endothelium
what does TH1 cells secrete
IL-2 for CD8+ t cell growth/activation
IFN-Y for MO M1 activation
cytokines that induce vasodilation
histamine
serotonin
PGI2/ D2/ E2
what are the chemotactants the recruit neutrophils in chemotaxis
IL-8
LTB4
C5a
bacterial products
source and function of histamine
mast cells, basophils, platelets
-dilation, increased permeability, endothelial activation (p-selection release)
function and source of IL-12
APCs (macrophages, dendritic cells)
stimulate TH1 cell type to increase IFN production
what type of inflammation associated with chronic inflammation and what are the hallmarks
granulomateous
- epitheloid histiocytes with pink cytoplasm
- multi-nucleated giant cells with lymphocyte rims
ECM deposition depends on a balance of what factors
TGF - fibrogenic agent
MMP - ECM degradation
TIMPS - MMP inhibitor
cytokines that induce pain
bradykinin
PGE2
what are the components of ECM
collagen
lamnin
proteoglycans
fibroblasts
source of kinins and complement
plasma produced in liver
what is the left shift
seen in luekocytosis of the acute phase response
-when huge increase in neutrophils initially causes subsequent increase in immature neutrophils in blood
secretion of M2 and function
TGF-B and GF = tissue repair and fibrosis
IL-10 and TGF-B = anti-inflammatory
describe how fever is caused in an inflammatory response
IL-1 and TNF travel to the perivasculature of the hypothalamus and subsequently increase COX activity which produces PGE2 which induces an increase in set point of body temperature
what are the 5 R’s of inflammatory reaction
- recognition
- recruitment
- removal of pathogen
- regulation of response
- repair
which APPs are activated by IL-6 and opsonize comeplement and clear necrotic cells
CRP and fibrinogen
cytokines that induce fever
IL-1
TNF
PGE2
what are the morphologic patterns of acute inflammation
serous
fibrinous
ulcer
purulent (suppurative)
what does TH2 secrete
IL-4 = IgG/E class switching IL-5= eosinophil activation, IgA switching IL-10 = inhibits TH1, anti inflammatory IL-13 = M2 activation
what causes activation of CD4+ tcells and what is its function
MHCII APC presentation of extracellular antigen = binding of B7 (on APC) to CD28 (on t-cell)
TH1 = M1 MO activation, CD8+ T cell activation
TH2= helps B cell activation, and M2 MO activation
what pharmacological agents can be used asthma treatment
- lipooxgenase inhibitor
- inhibit bronchospasm effects of Its - LT antagonist
* NSAIDs don’t affect lipoogenases or Its
what are the mediators that induce P-selectin release from webel palade bodies
histamine and thrombin
what is fibrinous acute inflammation pattern
inflammation of the lining of body cavities causes leakage of proteins such as fibrinogen (a procoagulant) leading to FIBROUS EXUDATE
-can lead to fibrosis if extensive leakage with activation
“bread and butter pericarditis”
which growth factor is responsible for endothelial proliferation ? angiogenesis ?
proliferation
VEGF
angiogenesis
FGF
define dehiscence
wound opening
define pus
a purulent inflammatory exudate rich in dead neutrophils and other WBCs and microbe debris
what is the process of regeneration and repair
regeneration = uninjured cell proliferation and stem cell maturation repair= deposition of new connective tissue
what condition is associated with C1 inhibitors of complement
- Block C1 activation in classic pathway
- hereditary angioedema
function of DAF and CD59 and what disease is associated with it
DAF-prevents C3 converstase function
CD59 prevents MAC formation
both are anchored by GPI and GPI deficiency = paroxysmal nocturnal hemoglobinuria
source of TNF
macrophages
mast cells
T-cells
what process of wound healing is responsible for some edema
angiogenesis
bc vasodilation by VEGF
describe the process of rolling
a component of neutrophil membrane (sialyl lewis X) will bind to selectins on endothelial wall and causing slowing of neutrophil movement
- P-selectins are induced by histamine and thrombin release on webel-palade bodies
- E-selectins and L-selectins are upregulated by TNF and IL-1
define hypertrophic scar
excess T1 collagen = large scar
what are the types of stimuli that cause an inflammatory reaction
microbial infection
tissue necrosis (from cell injury)
foreign bodies
immune reaction (hypersensitivity run from allergies or autoimmune)
describe oxygen dependent phagocytic killing
ROS
-O2–(NADPH oxidase)–> O2- —(SOD)—> H202—(MPO)–> HOCL
NO
-Arginine —(iNOS)—> NO
NO converts O2- –>ONOO- (peroxynitrate)
NO causes vasodilation
corticosteroid inhibit what
gene transcription of Cycloogenases (COX) and lipooxygenases
-decreases LTs and PGs which affects inflammation
describe the 3 step process of phagocytosis induced by neutrophils in acute inflammation
- recognition
- requires neutrophil activation by phagocytic receptor microbial recognition (mannose receptor and scaveneger receptor), increased intracellular Ca2+, and protein kinase C and phospholipase A2 activation. - vacuole engulfment extension of pseudopod that engulfs microbe into phagosome. phagosome combines with lysosome to make phagolysosome
- killing by phagolysosome
- O2 dependent (ROS or NO)
- O2 independent (lysosomal enzymes)
*enhanced by opsonins (MBL, C3b, IgG)
how does thrombin activate the inflammatory response
intiate the release of P-selectins which induces activation of endothelium
source and function of IFN-Y
acute inflammation
T-cells
-macrophage and neutrophil recruitment
chronic
T-cells and NK cells
-activate MO killing function
*stimulated by IL-12 from macrophages
what are the phagocytic opsonins
(MBL, C3b, IgG)
define keloid
excess T3 collagen = large scar
macrophages kill by what mechanism of phagocytosis
O2 independent killing (lysozyme)
what do macrophages release for WBC recruitment and inflammation
TNF
IL-1
source and function of IL-6
macrophages
-acute phase response
which PG is prostacyclin and what is its function
PGI2 = prostacyclin
- inhibits platelet aggregation (opposite of TXA2)
- vasodilation and increased permeability
what is septic shock? and what is it caused by?
caused by pathogens and increased IL-1 / TNF
hypotensive stoke intracellular coagulation (DIC) metabolic dysfunction (hyperglycemia)
details of the last step of scar formation
- ECM protein deposition
- T3 —> T1 collagen by collagnease and zinc cofactor
what are the cardinal signs of inflammation
redness (rudor) warmth (calor) swelling (tumor) pain (dolor) -fever
*loss of function
function of mast cells
FCeRI binds to FC receptor of IgE and induces release of histamine and PGs for pro-inflammatory response
what is the purulent acute inflammation pattern
pus exudate (dead neutrophils)
-associated with abscess and bacterial infection of pyogenic bacteria(
(-seen with staph and liquefactive necrosis )
_____ kill by ROS species using phagocytic receptors
granulocytes
*MPO is a granule
what is the oxidative burst of phagocytic killing
conversion of O2 to O2- by NADPH oxidase
what are the steps in scar formation
- MO M2 clear debris and secrete GF and TGF-B for fibroblast migration and proliferation
- angiogenesis
- deposition of CT
i. granulation tissue - fibroblast proliferation
ii. scar formation - ECM deposition
function of TGF-B
- fibroblast migration/ chemotaxis
- ECM protein production/ deposition
- anti-inflammatory
what are the 3 steps in the acute phase response ? and what is it induced by ?
- fever (induced by endogenous and exogenous pyrogens)
- acute phase protein release
- leukocytosis (extreme increase in WBC )
*induced by TNF, IL-1, IL-6
what induces M1 formation? M2 formation ?
M1
- IFN-Y from Tcells
- microbes
M2
- IL-4
- IL-5
- IL-13
function of IL-1
fever
adhesion (upreg selectins and CAMs)
Th17 activation for acute inflammation
function of TNF
adhesion (upreg E selections and CAMs)
decreasing appetite (other local and systemic effects)
WBC activation
fever
what are the steps in neutrophil recruitment
- margination
- rolling
- adhesion
- diapedesis
- chemotaxis
* phagocytosis follows
what are the 3 fibroblast chemotactants
TGF-B
FGF
PDGF
sources of IL-1
macrophages
mast cells
endothelial cells
extent of cell injury in acute vs chronic inflammation
acute
-mild-self-limited tissue injury
chronic
-severe, progressive tissue injury
what is the ulcer acute inflammation pattern
sloughing of dead necrotic tissue due to decreased blood supply to area
(seen in T1DM)
what cytokine is a big component of creating the warmth, redness, and swelling seen in acute inflammation
histamine
what are the types of collagen and associated tissues
*from most strong to least 1- bone 2- cartilage 3-BVs, granulation tissue 4- basement membrane
describe B-cell maturation / activation process
immature B-cell–>naive B cell (IgM/IgD) –>activation by Ag binding and plasma cell production of more Cells; APC MHCII presentation and CD40 CD40L binding
*use IL-4/5 for isotype switching
what are the three possible outcomes of acute inflammation
- complete resolution (regeneration)
- healing repaid by connective tissue replacement (scarring)
- chronic inflammation
what are the acute phase (plasma) proteins increased in the acute phase response
CRP
fibrinogen
serum amyloid A
hepcidin
*made in the liver!
what is serous acute inflammation pattern
- exudation of TRANSUDATE into body cavities
ex: asitces
describe the process of margination
WBCs move from center of blood vessel to the periphery due to vasodilation and stasis of blood flow
process of forming granulation tissue in wound healing
- fibroblast deposition of T3 collagen
- capillary nutrient delivery
- myofibirllast contraction of wound
describe the relationship of arachidonic acid , COX, lipooxgenases, and TA2
phospholipid membranes have arachidonic acid which is cleaved/activated by phospholipase A2 to become either cyclooxgenases or lipooxgenases
COX
- become Prostagladins (PGI2/E2/D2)
- produce thromboxane A2 which causes vasoconstriction and platelet aggregating in primary hemostasis
LIPOX
- become leukotrienes (LTB4, D4, E4, C4)
- become LXA4/B4 which inhibit inflammation
**phospholipase A2 is inhibitd by steroids
labile vs stable vs permanent tisses
labile = continuously dividing tissues capable of regeneration (ex: hemipoetic cells in bone marrow and surface epithelium )
stable= tissues normally in G0 stage but can proliferate in response to injury; limited regeneration ability (ex: liver, endothlial cells, fibroblasts, organ parenchyma, smooth M. cells)
permanent= tissues with no post-natal cell proliferation and no regeneration capacity (ex: heart , nerves, skeletal M.)
what CTK recruits eosinophils
IL-5
location of langerhans cells? alveolar Macrophages? histiocytes?
- skin
- lungs
- spleen and LNs
what is a pro inflammatory protein made in the liver associated with DIC and activates coagulation and fibrinolytic systems with complement and Kinins
hageman factor
*activated with subendothelial exposure
causes of exudate vs transudate
exudate (extracellular fluid high in protein and cell debris)
-caused by increased vascular permeability (as seen in acute inflammation)
transudate (extracellular fluid low in proteins)
-caused by change in osmotic equilibrium across capillary (increased hydrostatic pressure or decreased oncotic pressure)
local/systemic signs in acute vs chronic inflammation
more prominent in acute inflammation (such as edema) vs chronic
what is responsible for decreasing iron availability and causing anemia in chronic inflammation
hepcidin (iron regulator protein, increased in acute phase response )
what are the two types of granulomatous inflammation and what are there hallmark differences
non-casseating
-no central necrosis
cosseting
-central necrosis
what cell uses major basic protein and what is its function
eosinophils
-killls microbe by oxygen independent phagocytic killing
healing by 1st intention vs 2nd intention of epithelial injury
1st intention **FIBROUS UNION
epithelial layer damage; tissue surfaces have been approximated; used when there has been very little tissue loss; leads to less scar formation
2nd intention
- extensive injury, granulation tissue fills defect and results in more scarring and myofibrilblast attempt to decrease wound size
- *WOUND CONTRACTION
secretion of M1 MOs and function
IL-12 = induction of more IFN-Y
ROS , NO, and lysoszymes =l killing
IL-1/ TNF = fever and inflammation
IL-23 = more inflammation
what are NETs function in acute inflammation
-fibrin nets made by neutrophils in response to pathogens that hold anti-microbial enzymes/granules near site of infection and are used as a net catch to trap the microbe for killing
what is the source of PGs and LTs
mast cells and leukocytes
morphologic features of chronic inflammation
- persistent infection/toxic exposure with extensive tissue destruction
- attempts of tissue repair by angiogenesis and fibrous
- mononuclear (macrophage, plasma cells, and lymphocytes) infiltration
what are the 3 major components of acute inflammation and their consequences
- vasodilation
- leads to increased blood flow through arteriole and to blood stasis at the post capillary venule - increased vascular permeability
- leads to exudative edema - WBC emigration from blood and accumulation at injury followed by activation of elimination pathogenesis
what is the normal amount of WBC in the body ? what is the amount seen in leukemiod reaction of luekyocytosis ?
4000-11000
40,000- 100,000
IL-17 source and function
T-Cell (Th17)
- nuetrophil recruitment
- macrophage recruitment
- *increases acute inflammation and chronic inflammation
- *Th17 stimulated by IL-1
what is needed for proper regeneration
ECM integrity
stem cells
growth factors for cell proliferation
**factors = intrinsic proliferative capacity
source and function of platlet-activating factor (PAF)
leukocytes and mast cells
- vasodilation
- increased vascular permeability
- leukyeocyte ahdesion
- chemotaxis
- degranulation
- oxidative burst **!!!!!!!!!
what does macrophages release that continues neutrophil recruitment and purulent inflammation
IL-8
