Lecture 25 Flashcards
Two major roles of inflammation
- inflammation is responsible for eliminating infection
- inflammation is also responsible for repairing
What are the classical local signs of inflammation?
heat (warmth)
redness (erythema)
swelling (edema)
pain
loss of function
What are the two major components of inflammation that contribute to these signs of inflammation?
- vascular changes
- cellular events
Vascular changes associated with inflammation
Vasodilation: diameter increases, fluid velocity decreases
Increased viscosity (thickness): due to fluid loss of tissues. Molecules leave the bloodstream going through capillaries during the inflammation.
margination
5 mechanisms underlying increased vascular permeability during acute inflammation
Endothelial cell contraction/retraction leading to intercellular gaps that leak fluid
Direct endothelial injury
Leukocyte-dependent endothelial cell damage due to release of toxic mediators by leukocytes
Increased fluid through endothelial cells (transcytosis)
leakage from new blood vessels that form at the site of injury
Effects of vascular changes
Release of transudate: small holes forming in the capillaries
Release of exudate: bigger holes proteins rich fluid with numerous cells
These events result in edema: accumulation of fluid and swelling at the site of infection
What are the events occuring in leukocyte migration?
- margination and rolling
- adhesion
- firm adhesion
- transmigration
- chemotaxis and activation
- phagocytosis
- degranulation
- phagocytosis stumules and oxidative burst
- proteins present in the lysosomes also help destroy foreign bodies
Margination and rolling include
changes in vascular dilation that causes changes in the blood flow and white blood vessels to flow along the inner wall of blood vessels
leukocytes tumble along the inner wall of blood vessels (rolling)
Rolling enables leukocytes to transiently adhere to endothelial cells
Adhesion is mediated by
s-Lex modified glycoproteins on leukocytes bind to E and P selectin which is happening at sites of inflammation
Firm adhesion
transient binding slows leukocyte tumbling, which enables leukocytes to firmly adhere via strong binding of endothelial cells
Integrins help bind Ig superfamily molecules (ICAM-1 and VCAM-1) on endothelial cells
Transmigration
leukocytes moving through the endothelial barrier by squeezing in between endothelial cells through intercellular junctions
express an enzyme called collagenases to degrade basement membranes
Chemotaxis and activation
Leukocytes migrate to the site of inflammation by following an increasing chemical gradient
Gradient can be composed of: bacterial peptides, complement system components, cytokines, chemokines, and leukotrienes
Mechanism of Phagocytosis
Leukocytes can bind and ingest most microorganisms and dead cells via specific surface receptors that can recognize host cells
Opsonins
coat microbes and target them for phagocytosis, this is known as opsonization
IgG, C3 breakdown products, and collectins can bind to microbial cell-wall sugar groups and serve as the most important opsonins
Engulfment is triggered by opsonin binding
Degranulation
fusion of the phagosome with a lysosome which will result in the formation of a phagolysosome
causes the destruction of the phagosome contents by the contents of the lysosome
