Inflammation repair Flashcards
acute inflammation
- rapid onset
- short duration (few minutes to days)
- fluid and plasma protein exudation
- predominantly neutrophilic leukocyte accumulation
chronic inflammation
- more insidious
- longer duration (days to years)
- influx of lymphocytes and macrophages
- vascular proliferation and fibrosis (scarring)
circulating inflammatory cells
neutrophils lymphocytes monocytes eosinophils basophils
extravascular inflammatory cells
macrophages
mast cells
dendritic cells
cardinal signs of inflammation?
heat redness swelling pain loss of funcion
calor= rubor= tumor= dolor= functio laesa=
heat redness swelling pain loss of funcion
transudate
- ultrafiltrate of blood plasma
- low protein conent
- results from hydrostatic alterations across the vascular endothelium
- permeability of the endothelium is normal
- may accumulate in various non-inflammatory conditions
exudate
- protein rich fluid and cellular debris
- result of increased vascular permeability
- typical of inflammation
mechanisms of increased vascular permeability
1) endotheliall cell retraction
- -immediate Transient response
- -caused by chemical mediators (histamine, bradykinin, leukotrienes)
2) endothelial injury
- -immediate sustained response
3) increased transcytosis
- -mediated by vascular-endothelial growth factor (VEGF)
4) leakage from new blood vessels
- -angiogenesis during wound healing
BV + fibroblasts= _____ tissue
granulation tissue
leukocyte recruitment
- margination
- rolling (SELECTIN family of adhesion molecules)
- adhesion (integrins on leukocytes)
- transmigration (chmokines and CD31)
- chemotaxis
leukocyte activation
- phagocytosis
- killing and degradation of microbes
another term for transmigration?
diapedesis
complement component C5a and lipoxygenase pathway of AA metabolism (LTB) are ______ agents
chemotaxic
when does neutrophils predominate over monocytes in inflammation response? which one survives longer?
neutrophils predominate in first 24 hours!
**monocytes survive longer
3 steps of phagocytosis
1) recognition and attachment
2) engulfment and formation of phagocytic vacuole
3) killing and degradation
what do opsonins do?
host proteins that coat microbes and target them for phagocytosis (by a process called opsonization)
important opsonins
- IgG antibodies
- breakdown products of complement protein C3
- collectins
leukocyte receptors
- Fc receptor for IgG
- complement receptors (CR 1 and 3)
- C1q receptors for collectins
myeloperoxidase
an enzyme contained in neutrophile lysosomes
*converts H2O2 to HOCl (powerful antimicrobial agant and oxidant)
dead microorganisms are degraded by _______
lysosomal acid hydrolases (elastase)
besides lysosomal acid hydrolases, what are other antimicrobials in leukocyte granules?
- bactericidal permeability-increasing protein
- lysozyme
- major basci protein
- defensins (create holes in membranes)
phagocytic mechanisms are primarily confined to ________. but what about leukocytes?
phagolysosome
* but leukocytes may secrete enzymes and antimicrobial peptides into the extracellular space
neutrophil extracellular traps
- nuclear chromatin + granule protein
- detected in blood neutrophils during sepsis
- fibrilar networks produced in response to infectious pathogens
contents of lysosomal granules released in ECM?
- regurgitation = vacule open to outside
- frustrated phagocytosis =substances not easily ingested
LAD-1 vs LAD-2 defects in eukocyte adhesion
LAD-1 =defective syntehsis of CD18 B subunit of LFA-1 and Mac-1= IMPAIRED ADHESION
LAD-2 =defect in fucose metabolism- absence of sialyl-Lewis X (polysac surface of WBCs)
chronic granulomatous disease
results from deficiency in a component of the phagocyte oxidase— no ROS
Chediak-Higashi Syndrome autosomal recessive disease
- impaired fusion of lysosomes with phagosomes
- secretion of lytic secretory granules by cytotoxic T-lymphocytes
- severe immunodeficiency
resolution = _____ and _____ simutaneously
regeneration and repair
fibrosis
extensive scarring inorgens
-occurs in organs where there is lots of CT; may compromise function (heart attack)
what are the 3 morphological patterns of acute inflammation?
1) serous
- -watery, protein poor, mesothelial cells lining the cavities
2) fibrous
- -more serious, pink mesh looking, fibrin removed by macrophages (resolution)
3) suppurative (purulent)
- -PUS, strep and staph, cellulitis
blister vs bula
blister= smaller than 1cm bula= larger than 1cm
think what when you hear purulent?
pus (cellulitis)
ulcer vs erosion
ulcer= complete loss of epithilium, local, acute and chronic inflammation coexist
erosion= thining of epithium, larger earea
cell derived mediators
1) vasoactive amines
- -histamine and serotonin
2) arachidonic acid metabolites
- - prostaglandins, leukotrienes, lipoxins
3) platelet-activating factor
4) cytokines
- - tumor necrosis factor, interleukin-1, chemokines
5) ROS
6) nitric oxide
7) lysosomal enzymes of leukocytes
8) neuropeptides
histamine
- stored most commonly in mast cells (and basophiles and platelets)
- released in response to injury, immune reactions, neuropeptides, cytokines
serotonin
preformed mediators stored in platelets (also some in brain and GI)
- causes vasoconstriction during clotting
- released during platelet aggregation
arachidonic acid metabolites
- affect inflammation and hemostasis
- WBCs, platelets, and mast cells are major sources
- AA= component of cell membrane phospholipids
- released by action of phospholipases
COX1 vs COX2 inhibitors
COX1= inhibition of COX1 is bad bc is protects stomach against acid
COX2= is better to block bc it is not produced in normatl tissues
aspirin and NSAID inhibit ________ and treat?
inhibit cyclooxygenase (COX 1 and 2)
- block PG synthesis
- treat pain and fever
glucocorticoids inhibit what part of arachidonic acid (AA) pathway?
inhibits phospholipases A2–> inhibits AA release and production of prostaglandins and leukotrienes bc it is at the TOP of the pathway
what are cytokines?
role in acute and chronic inflammation?
mediators of inflammation and immune response
- acute inflammation = tumor necrosis factor (TNF), IL 1 and 6
- chronic = interferon- gamma and IL-12
IL-17 produced by?
T-cell mostly
TNF and IL-1 primary role?
endothelial activation and may enter circulation to induce systemic acute phase reaction (cachexia, lethargy)
- TNF= inrease thromogenicity and neutrophil aggregation
- IL-1 = fibroblast activation
cachexia
metabolic wasting with chronic illness
RANTES
regulates on activation, Normal T-cell Expressed and Secreted
*chemotactic for memory CD4+ T-cells and monocytes
eotaxin
chemotactic for eosinophils
ROS released from? stored in?
- released from neutrophils and macrophages
- within lysosomes
- short lived
- stored in liver
nitric oxide
short-lived, soluble, free radical
- in CNS regulates neurtransmitter release and blood flow
- produced by endothelial cells
- antagonizes platelet activation
what are the lysosomal enzymes of leukocytes?
1) acid proteases - active within phagolysosomes
2) neutral protease
- -cleaves C3 and C5 to C3a and C5a
3) counteracted by antiproteases
- -alpha 1-antitrypsin (inhibits neutrophil elastase)
- -alpha 2- macrophages
substance P
is a neuropeptide
- transmits pain signals
- regulation of vessel tone
- modulate vascular permeability
what do complement proteins do upon activation?
- opsonize microbes to facilitate phagocytosis
- increase vascular permeability
- generation of membrane attack complex
inactive components of complement?
C1-C9
complement is activated how?
proteolysis leading to a cascade
activation of C3
C3 convertase –> C3a and C3b
1) classical pathway triggered by binding of C1 to Ag-Ab complexes
2) alternative pathway triggered by endotoxin, other cell wall components
3) lectin pathway: binding of plasma lectin to mannose residues on microbes
What makes up C5 convertase?
C3b binding to C3 convertase complex
C3b is deposited on surface of?
a microbe
C5 convertase–>
C5a and C5b –> assembly of C6-C9
MAC’s composition =
C5b- C6- C7- C8-C9n
C3a and C5a are both?
anaphylatoxins: mast cells release histamine and increase vascular permeability
C5a acitves ______ pathway of AA metabolism
lipoxygenase
decay accelerating factor
limits formation of C3 and C5 convertase. acquired deficiency of DAF–> paroxysmal nocturnal hemoglobinuria
Factor H
also limits convertase formation.
Hagemen factor or factor 12 (active form 12a) activates?
- kinin system
- clotting system
- fibrinolytic system
- complement system
Hagemen factor is synthesized where? activated when in contact with?
- synthesized in liver
- active when contacting collagen
factor 12a > ______ (factor 2) and _____ (factor 2a) > cleavage of ______ > _____ clot
factor 12a > prothrombin (factor 2) and thrombin (factor 2a) > cleavage of fibrinogen > fibrin clot
factor 10a
increase vascular permeability and WBC adhesion
factor 12a ultimately leads to?
bradykinin, which causes pain and has similar affects as histamine
bradykinin
causes paiin -similar affects as histamine 0increase vascular perm -arteriolar dilation -bronchial smooth muscle contraction
kallikrain has chemotactic activitiy and activates?
Hagement (12a) factor like a feed back loop
