Inflammation - Intro Flashcards
What are the cardinal signs of inflammation?
a. Heat, redness, swelling, pain, loss of function.
What are the protective effects of inflammation.
a. Important for removal of pathogens, remove necrotic debris, and tissue remodeling.
b. From notes: Destroys, dilutes, or walls off injurious agents. Initiates healing, tissue repair, and return to homeostasis.
Explain the main components of acute inflammation.
Increased vascular permeability
vasodilation
cytokine release from cell mediators of inflammation
fibroblast activation
removal of pathogens by phagocytes
fever
lymphocyte transmigration across blood vessels
migration to site of injury in the tissue.
From notes: plasma, circulating cells, blood vessels, cellular and extracellular components of connective tissue.
Define EDEMA
a. The exudation of proteinous material into the interstitial space. Edema can result from either increased vascular permeability or imbalanced osmotic and oncotic gradients due to a lack of protein. Can be exudate or transudate.
What’s the difference between EXUDATE and TRANSUDATE
Exudate has SG > 1.020. it is more proteineous than transudate. Exudate occurs due to increased vascular permeability due to either the inflammatory response to cytokines by the basement membrane (resulting in contraction) OR as a result of vascular damage.
Transudate has SG < 1.012, occurs when the osmotic and oncotic pressures are out of balance either due to high blood pressure or hypoproteinemia. With transudate, there is no damage to endothelial cells.
What is PUS?
a. A purulent exudate that is composed of dead neutrophils and dead cell debris that accumulates from the inflammatory efforts to remove a pathogen.
How do you describe a lesion that contains pus?
NOT Pus-sy! Suppurative inflammation (inflammation that contains pus) or purulent exudate.
What’s the sequence of vascular changes in ACUTE inflammation? ( ~ 7 steps)
- Pathogen is encountered or damage occurs to tissue
- cytokines are released from damaged tissue or tissue macrophage
- cytokines cause contraction, resulting in increased vascular permeability
- loss of fluid leads to increased viscosity of blood and stasis, allowing for lymphocytes to adhere to the endothelial surface
- cytokines upregulate expression of selectins and integrins to mediate lymphocyte migration
- lymphocytes respond to a chemical gradient of cytokines, transmigrate across the endothelial basement membrane through diapedesis
- migration to the area of tissue insult.
What are the mechanisms of vascular leakage?
- Leukocyte-mediated damage
- Endothelial contraction
- Direct endothelial injury
- Increased transcytosis
What is leukocyte-mediated damage?
When leukocytes release cytoplasmic granules into the extracellular space, leading to endothelial damage.
What is endothelial contraction?
A response to inflammatory cytokines, leading to an increase in interendothelial space.
What mediates endothelial contraction?
Mediated by histamine, bradykinins, and leukotrienes.
What is direct endothelial injury?
Direct damage causes necrosis and detachment.
Example: burns, lytic bacteria.
What is increased transcytosis?
Increased transport of fluid and protein through endothelial cells.
Explain the sequence of events involved in leukocyte extravasation.
- MARGINATION – blood stasis helps leukocytes stack up at periphery against vessel wall.
- ROLLING – Selectins mediate rolling along the endothelium along a chemical gradient.
- ADHESION - Mediated by integrins on the leukocytes and immunoglobulins on the endothelium. Leukocytes become firmly adhered to the endothelium.
- TRANSMIGRATION - Also called diapedesis. The leukocyte extends a pseudopod into the junction between the endothelial cells and squeezes through.
- MIGRATION - Leukocytes follow a chemical gradient to the site of injury.
What are the major classes of molecules involved in leukocyte rolling and adhesion.
Selectins, Integrins, Immunoglobulins, Chemokines
Selectins
on the leukocytes and the endothelial cells. Facilitate low-affinity rolling along the endothelium.
Integrins
on the leukocytes. Chemokines increase binding affinity of integrins, changing them from a low-affinity to a high-affinity state.
Immunoglobulins (with regard to leukocyte rolling and adhesion)
on the endothelial cells. Bind to integrins.
Chemokines/cytokines (with regard to leukocyte rolling and adhesion)
increase affinity of integrins and upregulate expression of selectins.
What is the consequence of deficiencies in leukocyte adhesion?
a. Frequent recurring infections.
b. The body cannot respond to pathogens or remove dead tissue.
Define chemotaxis.
The movement of a cell along a chemical gradient to reach a target tissue. In the case of inflammation, the leukocytes follow an increasing chemical gradient to reach the site of tissue insult.
What are the major classes of receptors involved in recognition of microbes and dead tissues?
a. Toll-Like Receptors
b. G-protein coupled receptors
c. Cytokine receptors
d. Opsonin receptors
What are the steps involved in PHAGOCYTOSIS?
- Phagocyte RECOGNIZES the pathogen from either TLRs, GPCRs, cytokine receptors, or opsonin receptors.
- Phagocyte extends a pseudopod around the pathogen, ENGULFING it, forming a PHAGOSOME.
- The phagosome fuses with a lysosome, forming a PHAGOLYSOSOME.
- The phagolysosome DIGESTS the pathogen with a respiratory burst (reactive-oxygen species) and lysosomal enzymes.
Be able to explain how inherited and acquired defects in leukocyte function cause disease.
Bone marrow suppression causes decreases in leukocyte formation. ( -penia)
What are the signals involved in terminating acute inflammation.
- Change from leukotrienes –> LIPOXINS.
(Lipoxins are anti-inflammatory.) - Mediators run out.
- TGF-Beta and IL-10 suppress the immune response.
- Neural impulses inhibit TNF release from macrophages.
