inhibited (e.g., complement regulatory proteins break up and degrade activated complement components).
System of checks and balances that regulates mediator actions.
-for acute inflammation, resident monocytes/macrophages turn into mast cells
(endothelium, smooth muscle, fibroblasts) and most epithelia
summary of acute response
LPS (bacterial component) elicits response from mast cells/macrophages,
which secrete cytokines/chemokines
that change the blood vessel;
these changes then allow substances in blood (macrophages, neutrophils), to enter the site of infection
macrophages/lymphocytes secrete IL-1 and TNF-alpha, which have powerful, widespread effects.
mast cells- found under epithelia filled with large vesicles containing histamine and other inflammatory paracrines
arachidonic acid derivatives- break down into prostaglandins and leukotrienes, both important in eliciting inflammatory response (asprin and NSAIDs)
C3a C5a complement peptides
may have the same actions as the initial mediators but may also have different and even opposing activities. Such cascades provide mechanisms for amplifying-or, in certain instances, counteracting-the initial action of a mediator.
Once activated and released from the cell, most of these mediators are short-lived
Acute inflammation steps
1. Vasodilation, increase blood flow
2. Changes in microvasculature -plasma proteins and leukocytes leave circulation
3. Emigration of leukocytes from microcirculation to site of injury
balance between hydrostatic pressure & outside pressure (colloid/osmotic pressure)
usually, very little passes between the two; when there is inflammation, there are 2 big changesk
increase in Blood Flow, heat and redness (erythema), vascular permiability
occurs via vasodilation and statis, as well as increased interendothelial spaces
an extravascular fluid that has a high protein concentration, contains cellular debris, and has a high specific gravity.
Its presence implies an increase in the normal permeability of small blood vessels in an area of injury and, therefore, an inflammatory reaction.
a fluid with low protein content (most of which is albumin), little or no cellular material, and low specific gravity.
It is essentially an ultrafiltrate of blood plasma that results from osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability.
denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate.
purulent exudate, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead
cells and, in many cases, microbes
journey of leukocytes from the vessel lumen to the interstitial tissue
1. In the lumen: margination, rolling, and adhesion to endothelium. Vascular endothelium in its normal, unactivated state does not bind circulating cells or impede their passage. In inflammation the endothelium is activated and can bind leukocytes, as a prelude to their exit from the blood vessels.
2. Transmigration: Migration across the endothelium and vessel wall
3. Migration in the tissues toward a chemotactic stimulus
adhesion mediated by selectin family:
P-selectin (platelets, endothelium),
L-selectin (leukocytes) bind other surface molecules (i.e.,CD34, Sialyl-Lewis X-modified GP)
Upregulated on endothelium by cytokines (TNF, IL-1) at injury sites
Rolling comes to a stop and adhesion results
Other sets of adhesion molecules participate:
Endothelial: ICAM-1, VCAM-1
Leukocyte: LFA-1, Mac-1, VLA-4
(ICAM-1 binds LFA-1/Mac-1, VCAM-1 binds VLA-4)
Ordinarily down-regulated or in an inactive conformation, but inflammation alters this
key to adhesion (stop rolling)
leukocytes express different integrins, which are all low affinity until cytokines are released;
cytokines change leukocytes to express high-affinity integrins
induces increased transcytosis (vascular permeability for vessel endothelium)
What leaves with vasodilatioin?
edema-escape of a protein-rich exudate into the extravascular tissue
-Fluid contains salts, high conc. of protein (incl. immunoglobulins)
-Neutrophils From WBCs population
-Macrophages Phagocytes; derived from monocytes
Acute Inflammation Hallmark
Main effector cells to mediate effects of acute inflammation
Important cause of neutrophilia
(increased neutrophils in the blood)
Short lived so have to be rapidly replaced
More numerous in the blood,
Respond more rapidly to chemokines,
Attach more firmly to the adhesion molecules that are rapidly induced on endothelial cells, such as P- and E-selectins.
After entering tissues, neutrophils are short-lived; they undergo apoptosis and disappear after 24 to 48 hours.
Monocytes not only survive longer but may proliferate in the tissues, and thus become the dominant population in chronic inflammatory reactions
-a characteristic way that a pathologist can diagnose/differentiate btw chronic & acute inflammation: initially, there is edema (fluid entering site of infection),
if infection isn’t cleared, then macrophages/monocytes are recruited
1. recognition of the offending agents, which deliver signals that
2. activate the leukocytes to ingest and destroy the offending agents and amplify the inflammatory reaction
once activated, cannot distinguish between host and offender
adhesion & migration
Leukocytes at injury site
Recognize and attach
Engulf (form phagocytic vacuole)
Reactive oxygen species formed through oxidative burst that includes: