Local Inflammation Flashcards
chronic inflammation
inflammation of prolonged duration (weeks to yrs)
acute inflammation
immediate & early response to cell injury (min to few days)
sentinel cells
resident tissue cells on epithelial surfaces
function of sentinel cells
- recognize PAMPs/DAMPs via cellular receptors
2. Release signaling molec. that recruit & activate other cells (effector cells)
Types of Sentinel cells
- Epithelial cells
- Mast cells
- Macrophages
- Dendritic Cells
Mast Cells
tissue cells w/ specialized granules that store some key inflammatory mediators
Dendritic cells
- tissue cells w/ long, slender branching cytoplasmic processes.
- specialized to capture antigens, present them to T-cells, & initiate adaptive immune response.
- recognize pathogens
- release inflammatory mediators
Chemical mediators of acute inflammation
- Complement C3a & C5
- histamine
- prostaglandin E2
- leukotriene B4
- Il-1, TNF-a
- chemokines
- bacterial peptides
Complement
Function: activate mast cells
Origin: Plasma
Source: Plasma
C3a + C5
Function: activate mast cells, chemotaxis
Origin: Tissue fluids
Source: Tissue fluids
histamine
Function: vasodilation, increase vascular permeability
Origin: Pre-formed
Source: mast cells
Inhibited by: antihistamines, glucocorticoids
prostaglandin E2
Function: enhances vasodilation
Origin: Cellular Synthesis
Source: mast cells, macrophages, other cells
Inhibited by: NSAIDs, glucocorticoids
leukotriene B4
Function: chemotaxis
Origin: cellular synthesis
Source: mast cells, macrophages, other cells
Inhibited by: NSAIDs (some), glucocorticoids
IL-1, TNF-a
Function: induce endothelial adhesion molecules
Origin: cellular synthesis
Source: Mast cells, macrophages, other cells
Inhibited by: glucocorticoids
chemokines
Function: chemotaxis
Origin: cellular synthesis
Source: many cells
Inhibited by: glucocorticoids
bacterial peptides
Function: chemotaxis
Origin: bacterial
Source: bacteria
Microvascular Events of Inflammation
- Vasodilation
- Endothelium leaky to plasma & plasma proteins
- Diapedesis (leukocytes exit from venules)
- Neutrophils emigrate initially b/c of lg #s
- Monocytes & lymphocytes emigrate
How do you tell how long inflammation has been present?
the types of cells present in the tissue
Vasodilation
Consequence: redness
Functional role: ^ blood flow to infection site
Mechanism: relaxation of pre-capillary sphincter in arterioles
Chemical Mediators of Vasodilation
histamine, serotonin, prostaglandin E2
Increased Vascular Permeability
Consequence: Swelling
Functional Role: recruitment of antimicrobial plasma proteins
Mechanism: several mechansims, including gaps b/n endothelial cells
Chemical mediators of increased vascular permeability
histamine
Leukocyte Emigration
Consequence: Pus formation
Functional Role: recruit phagocytes
Mechanism: (1) adhesion to endothelium. (2) diapedesis. (3) chemotaxis
Chemical mediators of Leukocyte Emigration
Adhesion: histamine, serotonin, IL-1, TNF-a
Chemotaxis: chemokines, C5a, leukotriene B4, bacterial peptides
Inflammatory cytokines that act locally & distant
IL-1, TNF-a, IL-6, G-CSF
CNS effects of acute inflammation
fever, lethargy/somnolence, appetite loss, induction of glucocorticoid synthesis by adrenal cortex
Acute-Phase proteins
- proteins whose [plasma] ^ during acute inflammation
- made by hepatocytes
functions of Acute-Phase proteins
- Amplify host defenses
- PAMP recognition –> opsonization &/or complement activation
- Microbial killing (C3 & C4)
- Regulate host defenses (limit inflammation location)
- assist in tissue repair (fibrinogen)
Leukocytosis
elevated WBC count
caused by G-CSF
When would Systemic inflammatory responses most likely occur?
- infections of certain organs (uterus)
- severe local infections w/ certain pathogens
- bacteria/fungi in bloodstream
- severe traumatic tissue damage, even in absence of infection
Systemic Inflammatory Response Syndrome (SIRS)
clinical manifestation of systemic response to injury
Spesis
SIRS in association w/ bacterial, viral, protozoal, or fungal infection
(SIRS + infection)
Severe Sepsis
sepsis + evidence of organ dysfunction, hypoperfusion, or hypotension
Septic Shock
sepsis + hypotension despite adequate fluid resuscitation
Multiple Organ Dysfunction Syndrome (MODS)
altered organ function in acutely ill patient
Things involved in sepsis
cells (leukocytes, mast cell lymphocytes)
cytokines & chemokines
plasma enzyme systems (complement, coagulation, contact activation)
acute-phase proteins
organs
TNF-a
-its serum concentrations positively correlate w/ death in certain types of sepsis. (ie. parvo)
IL-1
synergizes w/ TNF-a in early sepsis.
could correlate w/ death at certain [serum]
